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Hemodynamic Nonlinearities Affect BOLD fMRI Response Timing and Amplitude
de Zwart, Jacco A; van Gelderen, Peter; Jansma, J Martijn; Fukunaga, Masaki; Bianciardi, Marta; Duyn, Jeff H
The interpretation of functional Magnetic Resonance Imaging (fMRI) studies based on Blood Oxygen-Level Dependent (BOLD) contrast generally relies on the assumption of a linear relationship between evoked neuronal activity and fMRI response. While nonlinearities in this relationship have been suggested by a number of studies, it remains unclear to what extent they relate to the neurovascular response and are therefore inherent to BOLD-fMRI. Full characterization of potential vascular nonlinearities is required for accurate inferences about the neuronal system under study. To investigate the extent of vascular nonlinearities, evoked activity was studied in humans with BOLD-fMRI (n=28) and Magnetoencephalography (MEG) (n=5). Brief (600-800 ms) rapidly repeated (1 Hz) visual stimuli were delivered using a stimulation paradigm that minimized neuronal nonlinearities. Nevertheless, BOLD-fMRI experiments showed substantial remaining nonlinearities. The smallest stimulus separation (200-400 ms) resulted in significant response broadening (15-20% amplitude decrease; 10-12% latency increase; 6-14% duration increase) with respect to a linear prediction. The substantial slowing and widening of the response in the presence of preceding stimuli suggests a vascular rather than neuronal origin to the observed non-linearity. This was confirmed by the MEG data, which showed no significant neuro-electric nonlinear interactions between stimuli as little as 200 ms apart. The presence of substantial vascular nonlinearities has important implications for rapid event-related studies by fMRI and other imaging modalities that infer neuronal activity from hemodynamic parameters. PMID:19520175
The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults
Cortese, Bernadette M.; Uhde, Thomas W.; Brady, Kathleen T.; McClernon, F. Joseph; Yang, Qing X.; Collins, Heather R.; LeMatty, Todd; Hartwell, Karen J.
Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor + picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multi-sensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784
Detection and characterization of single-trial fMRI bold responses: paradigm free mapping.
Gaudes, César Caballero; Petridou, Natalia; Dryden, Ian L; Bai, Li; Francis, Susan T; Gowland, Penny A
This work presents a novel method of mapping the brain's response to single stimuli in space and time without prior knowledge of the paradigm timing: paradigm free mapping (PFM). This method is based on deconvolution of the hemodynamic response from the voxel time series assuming a linear response and using a ridge-regression algorithm. Statistical inference is performed by defining a spatio-temporal t-statistic and by controlling for multiple comparisons using the false discovery rate procedure. The methodology was validated on five subjects who performed self-paced and visually cued finger tapping at 7 Tesla, with moderate (TR = 2 s) and high (TR = 0.4 s) temporal resolution. The results demonstrate that detection of single-trial BOLD events is feasible without a priori information on the stimulus paradigm. The proposed method opens up the possibility of designing temporally unconstrained paradigms to study the cortical response to unpredictable mental events.
Prestimulus EEG alpha oscillations modulate task-related fMRI BOLD responses to auditory stimuli.
Walz, Jennifer M; Goldman, Robin I; Carapezza, Michael; Muraskin, Jordan; Brown, Truman R; Sajda, Paul
EEG alpha-band activity is generally thought to represent an inhibitory state related to decreased attention and play a role in suppression of task-irrelevant stimulus processing, but a competing hypothesis suggests an active role in processing task-relevant information - one in which phase dynamics are involved. Here we used simultaneous EEG-fMRI and a whole-brain analysis to investigate the effects of prestimulus alpha activity on the event-related BOLD response during an auditory oddball task. We separately investigated the effects of the posterior alpha rhythm's power and phase on activity related to task-relevant stimulus processing and also investigated higher-level decision-related processing. We found stronger decision-related BOLD activity in areas late in the processing stream when subjects were in the high alpha power state prior to stimulus onset, but did not detect any effect in primary sensory regions. Our phase analysis revealed correlates in the bilateral thalamus, providing support for a thalamo-cortical loop in attentional modulations and suggesting that the cortical alpha rhythm acts as a cyclic modulator of task-related responses very early in the processing stream. Our results help to reconcile the competing inhibition and active-processing hypotheses for ongoing alpha oscillations and begin to tease apart the distinct roles and mechanisms underlying their power and phase.
Using an achiasmic human visual system to quantify the relationship between the fMRI BOLD signal and neural response
Bao, Pinglei; Purington, Christopher J; Tjan, Bosco S
Achiasma in humans causes gross mis-wiring of the retinal-fugal projection, resulting in overlapped cortical representations of left and right visual hemifields. We show that in areas V1-V3 this overlap is due to two co-located but non-interacting populations of neurons, each with a receptive field serving only one hemifield. Importantly, the two populations share the same local vascular control, resulting in a unique organization useful for quantifying the relationship between neural and fMRI BOLD responses without direct measurement of neural activity. Specifically, we can non-invasively double local neural responses by stimulating both neuronal populations with identical stimuli presented symmetrically across the vertical meridian to both visual hemifields, versus one population by stimulating in one hemifield. Measurements from a series of such doubling experiments show that the amplitude of BOLD response is proportional to approximately 0.5 power of the underlying neural response. Reanalyzing published data shows that this inferred relationship is general. DOI: http://dx.doi.org/10.7554/eLife.09600.001 PMID:26613411
Olfactory responses to natal stream water in sockeye salmon by BOLD fMRI.
Bandoh, Hiroshi; Kida, Ikuhiro; Ueda, Hiroshi
Many studies have shown that juvenile salmon imprint olfactory memory of natal stream odors during downstream migration, and adults recall this stream-specific odor information to discriminate their natal stream during upstream migration for spawning. The odor information processing of the natal stream in the salmon brain, however, has not been clarified. We applied blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to investigate the odor information processing of the natal stream in the olfactory bulb and telencephalon of lacustrine sockeye salmon (Oncorhynchus nerka). The strong responses to the natal stream water were mainly observed in the lateral area of dorsal telencephalon (Dl), which are homologous to the medial pallium (hippocampus) in terrestrial vertebrates. Although the concentration of L-serine (1 mM) in the control water was 20,000-times higher than that of total amino acid in the natal stream water (47.5 nM), the BOLD signals resulting from the natal stream water were stronger than those by L-serine in the Dl. We concluded that sockeye salmon could process the odor information of the natal stream by integrating information in the Dl area of the telencephalon.
Baseline BOLD correlation predicts individuals' stimulus-evoked BOLD responses.
Liu, Xiao; Zhu, Xiao-Hong; Chen, Wei
To investigate whether individuals' ongoing neuronal activity at resting state can affect their response to brain stimulation, fMRI BOLD signals were imaged from the human visual cortex of fifteen healthy subjects in the absence and presence of visual stimulation. It was found that the temporal correlation strength but not amplitude of baseline BOLD signal fluctuations acquired under the eyes-fixed condition is positively correlated with the amplitude of stimulus-evoked BOLD responses across subjects. Moreover, the spatiotemporal correlations of baseline BOLD signals imply a coherent network covering the visual system, which is topographically indistinguishable from the "resting-state visual network" observed under the eyes-closed condition. The overall findings suggest that the synchronization of ongoing brain activity plays an important role in determining stimulus-evoked brain activity even at an early stage of the sensory system. The tight relationship between baseline BOLD correlation and stimulus-evoked BOLD amplitude provides an essential basis for understanding and interpreting the large inter-subject BOLD variability commonly observed in numerous fMRI studies and potentially for improving group fMRI analysis. This study highlights the importance to integrate the information from both resting-state coherent networks and task-evoked neural responses for a better understanding of how the brain functions.
The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans
Zhang, Xiaofeng; Toronov, Vladislav Y.; Fabiani, Monica; Gratton, Gabriele; Webb, Andrew G.
The integration of near-infrared (NIR) and functional MRI (fMRI) studies is potentially a powerful method to investigate the physiological mechanism of human cerebral activity. However, current NIR methodologies do not provide adequate accuracy of localization and are not fully integrated with MRI in the sense of mutual enhancement of the two imaging modalities. Results are presented to address these issues by developing an MRI-compatible optical probe and using diffuse optical tomography for optical image reconstruction. We have developed a complete methodology that seamlessly integrates NIR tomography with fMRI data acquisition. In this paper, we apply this methodology to determine both hemodynamic and early neuronal responses in the visual cortex in humans. Early results indicate that the changes in deoxyhemoglobin concentration from optical data are co-localized with fMRI BOLD signal changes, but changes in oxyhemoglobin concentration (not measurable using fMRI) show interesting spatial differences. PMID:21776185
The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans
NASA Astrophysics Data System (ADS)
Zhang, Xiaofeng; Toronov, Vladislav Y.; Fabiani, Monica; Gratton, Gabriele; Webb, Andrew G.
The integration of near-infrared (NIR) and functional MRI (fMRI) studies is potentially a powerful method to investigate the physiological mechanism of human cerebral activity. However, current NIR methodologies do not provide adequate accuracy of localization and are not fully integrated with MRI in the sense of mutual enhancement of the two imaging modalities. Results are presented to address these issues by developing an MRI-compatible optical probe and using diffuse optical tomography for optical image reconstruction. We have developed a complete methodology that seamlessly integrates NIR tomography with fMRI data acquisition. In this paper, we apply this methodology to determine both hemodynamic and early neuronal responses in the visual cortex in humans. Early results indicate that the changes in deoxyhemoglobin concentration from optical data are co-localized with fMRI BOLD signal changes, but changes in oxyhemoglobin concentration (not measurable using fMRI) show small spatial differences.
The association between cortisol and the BOLD response in male adolescents undergoing fMRI.
Keulers, Esther H H; Stiers, Peter; Nicolson, Nancy A; Jolles, Jelle
MRI participation has been shown to induce subjective and neuroendocrine stress reactions. A recent aging study showed that cortisol levels during fMRI have an age-dependent effect on cognitive performance and brain functioning. The present study examined whether this age-specific influence of cortisol on behavioral and brain activation levels also applies to adolescence. Salivary cortisol as well as subjective experienced anxiety were assessed during the practice session, at home, and before, during and after the fMRI session in young versus old male adolescents. Cortisol levels were enhanced pre-imaging relative to during and post-imaging in both age groups, suggesting anticipatory stress and anxiety. Overall, a negative correlation was found between cortisol output during the fMRI experiment and brain activation magnitude during performance of a gambling task. In young but not in old adolescents, higher cortisol output was related to stronger deactivation of clusters in the anterior and posterior cingulate cortex. In old but not in young adolescents, a negative correlation was found between cortisol and activation in the inferior parietal and in the superior frontal cortex. In sum, cortisol increased the deactivation of several brain areas, although the location of the affected areas in the brain was age-dependent. The present findings suggest that cortisol output during fMRI should be considered as confounder and integrated in analyzing developmental changes in brain activation during adolescence.
Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat
Deli, Levente; Gajári, Dávid; Dávid, Szabolcs; Pozsgay, Zsófia; Hegedűs, Nikolett; Tihanyi, Károly; Liposits, Zsolt
The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does
BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response to Thermal Stimulation of the Forepaws
Bosshard, Simone C.; Stuker, Florian; von Deuster, Constantin; Schroeter, Aileen; Rudin, Markus
Functional magnetic resonance imaging (fMRI) in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers. PMID:25950440
BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response to Thermal Stimulation of the Forepaws.
Bosshard, Simone C; Stuker, Florian; von Deuster, Constantin; Schroeter, Aileen; Rudin, Markus
Functional magnetic resonance imaging (fMRI) in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers.
Differential localization of pain-related neural responses during acupuncture stimulation using Blood Oxygen Level Dependent (BOLD) fMRI in a canine model.
Chang, Suk-Ki; Jahng, Geon-Ho; Lee, Sung-Ho; Choi, Il-Whan; Choi, Chi-Bong; Choi, Woo-Suk
The objective of this study was to differentiate the neuronal responses, which was related or unrelated, to pain associated with acupuncture stimulation, and to localize the brain regions with response to stimulation that is unrelated to pain by using Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). BOLD fMRI was performed in six normal healthy beagle dogs, during placebo and verum acupuncture stimulations, at the right side of BL60 (KunLun) acupoint before and after local anesthesia of the acupoint. The order of the four sessions was placebo; verum acupuncture stimulation; before local anesthesia; and followed by the same stimulation after local anesthesia. One-sample t-test analysis was performed to localize the activated or deactivated areas, during both pre-anesthesia and post-anesthesia. In order to compare the pre-anesthesia to post-anesthetic responses, and placebo to verum acupuncture stimulation, within-subject analysis was performed. The post-anesthetic verum acupuncture stimulation resulted in increased activations in the left somatic afferent area I and II, right visual and auditory association area, and the descending reticular activating system of the brainstem. In addition, differential areas during post-anesthesia compared to that of the pre-anesthesia were in the left olfactory peduncle and descending reticular activating system of the brainstem. These results indicate that the areas of specific neural pathway are considered to be unrelated to the pain response during acupuncture stimulation.
Reproducibility of BOLD, Perfusion, and CMRO2 Measurements with Calibrated-BOLD fMRI
Leontiev, Oleg; Buxton, Richard B.
The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index, n, defined as the ratio between fractional CBF change and fractional CMRO2 change. The combination of blood oxygenation level dependent (BOLD) imaging with CBF measurements from arterial spin labeling (ASL) provides a potentially powerful experimental approach for measuring n, but the reproducibility of the technique previously has not been assessed. In this study, inter-subject variance and intra-subject reproducibility of the method were determined. Block design %BOLD and %CBF responses to visual stimulation and mild hypercapnia (5% CO2) were measured, and these data were used to compute the BOLD scaling factor M, %CMRO2 change with activation, and the coupling index n. Reproducibility was determined for three approaches to defining regions-of-interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2) BOLD-activated voxels from a separate functional localizer, and 3) CBF–activated voxels from a separate functional localizer. For estimates of %BOLD, %CMRO2 and n, intra-subject reproducibility was found to be best for regions selected according to CBF activation. Among all fMRI measurements, estimates of n were the most robust and were substantially more stable within individual subjects (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The stability of n across days, despite wider variability of CBF and CMRO2 responses, suggests that the reproducibility of blood flow changes is limited by variation in the oxidative metabolic demand. We conclude that the calibrated BOLD approach provides a highly reproducible measurement of n that can serve as a useful quantitative probe of the coupling of blood flow and energy metabolism in the brain. PMID:17208013
Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD fMRI.
Leontiev, Oleg; Buxton, Richard B
The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation can be characterized by an empirical index, n, defined as the ratio between fractional CBF change and fractional CMRO(2) change. The combination of blood oxygenation level dependent (BOLD) imaging with CBF measurements from arterial spin labeling (ASL) provides a potentially powerful experimental approach for measuring n, but the reproducibility of the technique previously has not been assessed. In this study, inter-subject variance and intra-subject reproducibility of the method were determined. Block design %BOLD and %CBF responses to visual stimulation and mild hypercapnia (5% CO(2)) were measured, and these data were used to compute the BOLD scaling factor M, %CMRO(2) change with activation, and the coupling index n. Reproducibility was determined for three approaches to defining regions-of-interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2) BOLD-activated voxels from a separate functional localizer, and 3) CBF-activated voxels from a separate functional localizer. For estimates of %BOLD, %CMRO(2) and n, intra-subject reproducibility was found to be best for regions selected according to CBF activation. Among all fMRI measurements, estimates of n were the most robust and were substantially more stable within individual subjects (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The stability of n across days, despite wider variability of CBF and CMRO(2) responses, suggests that the reproducibility of blood flow changes is limited by variation in the oxidative metabolic demand. We conclude that the calibrated BOLD approach provides a highly reproducible measurement of n that can serve as a useful quantitative probe of the coupling of blood flow and energy metabolism in the brain.
On the Stability of BOLD fMRI Correlations.
Laumann, Timothy O; Snyder, Abraham Z; Mitra, Anish; Gordon, Evan M; Gratton, Caterina; Adeyemo, Babatunde; Gilmore, Adrian W; Nelson, Steven M; Berg, Jeff J; Greene, Deanna J; McCarthy, John E; Tagliazucchi, Enzo; Laufs, Helmut; Schlaggar, Bradley L; Dosenbach, Nico U F; Petersen, Steven E
Measurement of correlations between brain regions (functional connectivity) using blood oxygen level dependent (BOLD) fMRI has proven to be a powerful tool for studying the functional organization of the brain. Recently, dynamic functional connectivity has emerged as a major topic in the resting-state BOLD fMRI literature. Here, using simulations and multiple sets of empirical observations, we confirm that imposed task states can alter the correlation structure of BOLD activity. However, we find that observations of "dynamic" BOLD correlations during the resting state are largely explained by sampling variability. Beyond sampling variability, the largest part of observed "dynamics" during rest is attributable to head motion. An additional component of dynamic variability during rest is attributable to fluctuating sleep state. Thus, aside from the preceding explanatory factors, a single correlation structure-as opposed to a sequence of distinct correlation structures-may adequately describe the resting state as measured by BOLD fMRI. These results suggest that resting-state BOLD correlations do not primarily reflect moment-to-moment changes in cognitive content. Rather, resting-state BOLD correlations may predominantly reflect processes concerned with the maintenance of the long-term stability of the brain's functional organization.
fMRI at High Spatial Resolution: Implications for BOLD-Models
Goense, Jozien; Bohraus, Yvette; Logothetis, Nikos K.
As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI. PMID:27445782
FMRI, antipsychotics and schizophrenia. Influence of different antipsychotics on BOLD-signal.
Röder, Christian H; Hoogendam, Janna Marie; van der Veen, Frederik M
In the last decade, functional Magnetic Resonance Imaging (FMRI) has been increasingly used to investigate the neurobiology of schizophrenia. This technique relies on changes in the blood-oxygen-level-dependent (BOLD) - signal, which changes in response to neural activity. Many FMRI studies on schizophrenia have examined medicated patients, but little is known about the effects of antipsychotic medication on the BOLD-signal. In this review we investigated to what extent studies in patients with schizophrenia (SC), who were treated with different antipsychotics, could give insight in the effects of antipsychotics on the BOLD-signal. A PubMed search was performed using the search items "schizophrenia", "FMRI", "antipsychotics" and "schizophrenia", "BOLD", "antipsychotics". Only articles in which there were at least two groups of patients with different treatments or in which patients were scanned twice with different treatments were selected. 18 articles, published between 1999 and 2009, fulfilled these criteria. Paradigms and results of these studies were compared regarding differences induced by the administered antipsychotics. This analysis showed no general effect of antipsychotics on the BOLD-signal. However, there is some evidence that the extent of blockade of the dopamine (DA) D(2) receptor does influence the BOLD-signal. Higher affinity to the dopamine D2 receptor, as expressed by a higher/lower inhibition constant (Ki) seems to cause a decrease in BOLD-signal.
Differential Localization of Pain-Related and Pain-Unrelated Neural Responses for Acupuncture at BL60 Using BOLD fMRI
Jahng, Geon-Ho; Ryu, Chang-Woo; Ko, Chang-Nam; Park, Jung-Mi
The objective of this study was to differentiate between pain-related and pain-unrelated neural responses of acupuncture at BL60 to investigate the specific effects of acupuncture. A total of 19 healthy volunteers were evaluated. fMRI was performed with sham or verum acupuncture stimulation at the left BL60 before and after local anesthesia. To investigate the relative BOLD signal effect for each session, a one-sample t-test was performed for individual contrast maps, and a paired t-test to investigate the differences between the pre- and post-anesthetic signal effects. Regarding verum acupuncture, areas that were more activated before local anesthesia included the superior, middle, and medial frontal gyri, inferior parietal lobule, superior temporal gyrus, thalamus, middle temporal gyrus, cingulate gyrus, culmen, and cerebellar tonsil. The postcentral gyrus was more deactivated before local anesthesia. After local anesthesia, the middle occipital gyrus, inferior temporal gyrus, postcentral gyrus, precuneus, superior parietal lobule, and declive were deactivated. Pre-anesthetic verum acupuncture at BL60 activated areas of vision and pain transmission. Post-anesthetic verum acupuncture deactivated brain areas of visual function, which is considered to be a pain-unrelated acupuncture response. It indicates that specific effects of acupoint BL60 are to control vision sense as used in the clinical setting. PMID:23853664
Matched-filter acquisition for BOLD fMRI.
Kasper, Lars; Haeberlin, Maximilian; Dietrich, Benjamin E; Gross, Simon; Barmet, Christoph; Wilm, Bertram J; Vannesjo, S Johanna; Brunner, David O; Ruff, Christian C; Stephan, Klaas E; Pruessmann, Klaas P
We introduce matched-filter fMRI, which improves BOLD (blood oxygen level dependent) sensitivity by variable-density image acquisition tailored to subsequent image smoothing. Image smoothing is an established post-processing technique used in the vast majority of fMRI studies. Here we show that the signal-to-noise ratio of the resulting smoothed data can be substantially increased by acquisition weighting with a weighting function that matches the k-space filter imposed by the smoothing operation. We derive the theoretical SNR advantage of this strategy and propose a practical implementation of 2D echo-planar acquisition matched to common Gaussian smoothing. To reliably perform the involved variable-speed trajectories, concurrent magnetic field monitoring with NMR probes is used. Using this technique, phantom and in vivo measurements confirm reliable SNR improvement in the order of 30% in a "resting-state" condition and prove robust in different regimes of physiological noise. Furthermore, a preliminary task-based visual fMRI experiment equally suggests a consistent BOLD sensitivity increase in terms of statistical sensitivity (average t-value increase of about 35%). In summary, our study suggests that matched-filter acquisition is an effective means of improving BOLD SNR in studies that rely on image smoothing at the post-processing level.
Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal.
Hammett, Stephen T; Wall, Matthew B; Edwards, Thomas C; Smith, Andrew T
Creatine monohydrate is an organic acid that plays a key role in ATP re-synthesis. Creatine levels in the human brain vary considerably and dietary supplementation has been found to enhance cognitive performance in healthy individuals. To explore the possibility that the fMRI Blood Oxygen Level Dependent (BOLD) response is influenced by creatine levels, BOLD responses to visual stimuli were measured in visual cortex before and after a week of creatine administration in healthy human volunteers. The magnitude of the BOLD response decreased by 16% following creatine supplementation of a similar dose to that previously shown to increase cerebral levels of phosphocreatine. We also confirmed that cognitive performance (memory span) is increased. These changes were not found in a placebo group. Possible mechanisms of BOLD change are considered. The results offer potential for insight into the coupling between neural activity and the BOLD response and the more immediate possibility of accounting for an important source of variability during fMRI analysis in clinical studies and other investigations where between-subjects variance is an issue.
Linear and nonlinear relationships between visual stimuli, EEG and BOLD fMRI signals.
Liu, Zhongming; Rios, Cristina; Zhang, Nanyin; Yang, Lin; Chen, Wei; He, Bin
In the present study, the cascaded interactions between stimuli and neural and hemodynamic responses were modeled using linear systems. These models provided the theoretical hypotheses that were tested against the electroencephalography (EEG) and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data recorded from human subjects during prolonged periods of repeated visual stimuli with a variable setting of the inter-stimulus interval (ISI) and visual contrast. Our results suggest that (1) neural response is nonlinear only when ISI<0.2 s, (2) BOLD response is nonlinear with an exclusively vascular origin when 0.25
IRON fMRI measurements of CBV and implications for BOLD signal
Mandeville, Joseph B.
Changes in cerebral blood volume (CBV) and blood magnetization each induce changes in the transverse relaxation rate of MRI signal that are associated with changes in cerebral activity. BOLD signal, the preeminent method for non-invasive localization of task-induced brain function in human subjects, reflects of combination of changes in CBV and blood magnetization. Intravenous injection of paramagnetic contrast media, usually iron oxide particles surrounded by larger macromolecules, can overwhelm the BOLD response and sensitize signal to blood plasma volume, a method we have deemed "IRON" fMRI. The practical advantage of this technique is the ability to optimize blood magnetization at any echo time, enabling high detection power and the use of short echo times; for these reasons, IRON fMRI has become a valuable imaging tool in animals models. The temporal response of blood plasma volume is quite different from blood flow and BOLD signal; thus, CBV has been identified as a prominent source of transient features of the BOLD response. This article reviews the methodological advantages of the IRON method and how CBV measurements have informed our understanding of the BOLD response. PMID:22281669
How Predictable are "Spontaneous Decisions" and "Hidden Intentions"? Comparing Classification Results Based on Previous Responses with Multivariate Pattern Analysis of fMRI BOLD Signals
Lages, Martin; Jaworska, Katarzyna
In two replication studies we examined response bias and dependencies in voluntary decisions. We trained a linear classifier to predict "spontaneous decisions" and in the second study "hidden intentions" from responses in preceding trials and achieved comparable prediction accuracies as reported for multivariate pattern classification based on voxel activities in frontopolar cortex. We discuss implications of our findings and suggest ways to improve classification analyses of fMRI BOLD signals that may help to reduce effects of response dependencies between trials. PMID:22408630
Functional MRI during Hyperbaric Oxygen: Effects of Oxygen on Neurovascular Coupling and BOLD fMRI signals
Cardenas, Damon P.; Muir, Eric R.; Huang, Shiliang; Boley, Angela; Lodge, Daniel; Duong, Timothy Q.
Hyperbaric oxygen (HBO) therapy is used to treat a number of ailments. Improved understanding of how HBO affects neuronal activity, cerebral blood flow (CBF) and blood-oxygenation-level dependent (BOLD) changes could shed light on the role of oxygen in neurovascular coupling and help guide HBO treatments. The goal of this study was to test two hypotheses: i) activation-induced CBF fMRI response is not dependent on hemoglobin deoxygenation, and ii) activation-induced BOLD fMRI is markedly attenuated under HBO. CBF and BOLD fMRI of forepaw stimulation in anesthetized rats under HBO at 3 atmospheres absolute (ATA) was compared with normobaric air. Robust BOLD and CBF fMRI were detected under HBO. Inflow effects and spin-density changes did not contribute significantly to the BOLD fMRI signal under HBO. Analysis of the T2*-weighted signal at normobaric air and 1, 2 and 3ATA oxygen in the tissue and the superior sagittal sinus showed a strong dependence on increasing inhaled [O2]. Spontaneous electrophysiological activity and evoked local-field potentials were reduced under HBO. The differences between normobaric air and HBO in basal and evoked electrical activity could not fully account for the strong BOLD responses under HBO. We concluded that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism and that stimulus-evoked BOLD responses and the venous T2*-weighted signals still have room to increase under 3ATA HBO. To our knowledge, this is the first fMRI study under HBO, providing insights into the effects of HBO on neural activity, neurovascular coupling, tissue oxygenation, and the BOLD signal. PMID:26143203
Negative covariation between task-related responses in alpha/beta-band activity and BOLD in human sensorimotor cortex: an EEG and fMRI study of motor imagery and movements.
Yuan, Han; Liu, Tao; Szarkowski, Rebecca; Rios, Cristina; Ashe, James; He, Bin
Similar to the occipital alpha rhythm, electroencephalographic (EEG) signals in the alpha- and beta-frequency bands can be suppressed by movement or motor imagery and have thus been thought to represent the "idling state" of the sensorimotor cortex. A negative correlation between spontaneous alpha EEG and blood-oxygen-level-dependent (BOLD) signals has been reported in combined EEG and fMRI (functional Magnetic Resonance Imaging) experiments when subjects stayed at the resting state or alternated between the resting state and a task. However, the precise nature of the task-induced alpha modulation remains elusive. It was not clear whether alpha/beta rhythm suppressions may co-vary with BOLD when conducting tasks involving varying activations of the cortex. Here, we quantified the task-evoked responses of BOLD and alpha/beta-band power of EEG directly in the cortical source domain, by using source imaging technology, and examined their covariation across task conditions in a mixed block and event-related design. In this study, 13 subjects performed tasks of right-hand, right-foot or left-hand movement and motor imagery when EEG and fMRI data were separately collected. Task-induced increase of BOLD signal and decrease of EEG amplitudes in alpha and beta bands were shown to be co-localized at the somatotopic sensorimotor cortex. At the corresponding regions, the reciprocal changes of the two signals co-varied in the magnitudes across imagination and movement conditions. The spatial correspondence and negative covariation between the two measurements were further shown to exist at somatotopic brain regions associated with different body parts. These results suggest an inverse functional coupling relationship between task-induced changes of BOLD and low-frequency EEG signals.
Changes in fMRI BOLD dynamics reflect anticipation to moving objects.
Schellekens, W; Ramsey, N F; van Wezel, R J A; Raemaekers, M
The human brain is thought to respond differently to novel versus predictable neural input. In human visual cortex, neural response amplitude to visual input might be determined by the degree of predictability. We investigated how fMRI BOLD responses in human early visual cortex reflect the anticipation of a single moving bar's trajectory. We found that BOLD signals decreased linearly from onset to offset of the stimulus trajectory. Moreover, decreased amplitudes of BOLD responses coincided with an increased initial dip as the stimulus moved along its trajectory. Importantly, motion anticipation effects were absent, when motion coherence was disrupted by means of stimulus contrast reversals. These results show that human early visual cortex anticipates the trajectory of a coherently moving object at the initial stages of visual motion processing. The results can be explained by suppression of predictable input, plausibly underlying the formation of stable visual percepts.
Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat
Yang, Pai-Feng; Chen, You-Yin; Chen, Der-Yow; Hu, James W.; Chen, Jyh-Horng; Yen, Chen-Tung
The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways. PMID:23826146
Line scanning fMRI reveals earlier onset of optogenetically evoked BOLD response in rat somatosensory cortex as compared to sensory stimulation.
Albers, Franziska; Schmid, Florian; Wachsmuth, Lydia; Faber, Cornelius
The combination of optogenetic control and fMRI readout in the brain is increasingly used to assess neuronal networks and underlying signal processing. However, how exactly optogenetic activation or inhibition reproduces normal physiological input has not been fully unraveled. To assess details of temporal dynamics of the hemodynamic response, temporal resolution in rodent fMRI is often not sufficient. Recent advances in human fMRI using faster acquisition schemes cannot be easily translated to small animals due to smaller dimensions, fast physiological motion, and higher sensitivity to artefacts. Here, we applied a one dimensional line scanning acquisition with 50ms temporal resolution in rat somatosensory cortex. We observed that optogenetic activation reproduces the hemodynamic response upon sensory stimulation, but shows a 160 to 340ms earlier onset of the response. This difference is explained by direct activation of all opsin-expressing and illuminated cortical layers, while hemodynamic response to sensory stimulation is delayed during intracortical transmission between cortical layers. Our results confirm that optogenetic activation is a valid model for physiological neuronal input, and that differences in temporal behavior of only a few hundred milliseconds can be resolved in rodent fMRI.
Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex
Walter, Susanna A.; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria
Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms. PMID:26930498
Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI.
Kundu, Prantik; Inati, Souheil J; Evans, Jennifer W; Luh, Wen-Ming; Bandettini, Peter A
A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the
BOLD fMRI of visual and somatosensory–motor stimulations in baboons
Wey, Hsiao-Ying; Li, Jinqi; Szabó, C. Ákos; Fox, Peter T.; Leland, M. Michelle; Jones, Lisa; Duong, Timothy Q.
Baboon, with its large brain size and extensive cortical folding compared to other non-human primates, serves as a good model for neuroscience research. This study reports the implementation of a baboon model for blood oxygenation level-dependent (BOLD) fMRI studies (1.5 × 1.5 × 4 mm resolution) on a clinical 3 T-MRI scanner. BOLD fMRI responses to hypercapnic (5% CO2) challenge, 10 Hz flicker visual, and vibrotactile somatosensory–motor stimulations were investigated in baboons anesthetized sequentially with isoflurane and ketamine. Hypercapnia evoked robust BOLD increases. Paralysis was determined to be necessary to achieve reproducible functional activations within and between subjects under our experimental conditions. With optimized anesthetic doses (0.8–1.0% isoflurane or 6–8 mg/kg/h ketamine) and adequate paralysis (vecuronium, 0.2 mg/kg), robust activations were detected in the visual (V), primary (S1) and secondary (S2) somatosensory, primary motor (M cortices), supplementary motor area (SMA), lateral geniculate nucleus (LGN) and thalamus (Th). Data were tabulated for 11 trials under isoflurane and 10 trials under ketamine on 5 baboons. S1, S2, M, and V activations were detected in essentially all trials (90–100% of the time, except 82% for S2 under isoflurane and 70% for M under ketamine). LGN activations were detected 64–70% of the time under both anesthetics. SMA and Th activations were detected 36–45% of the time under isoflurane and 60% of the time under ketamine. BOLD percent changes among different structures were slightly higher under ketamine than isoflurane (0.75% versus 0.58% averaging all structures), but none was statistically different (P>0.05). This baboon model offers an opportunity to non-invasively image brain functions and dysfunctions in large non-human primates. PMID:20471483
Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study.
Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B
Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). In this study, we implemented a quantitative R(2)* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO(2) responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, +/-11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, +/-2.9) and CMRO(2) (+20.7%, +/-1.4), and caffeine decreased CBF (-34.5%, +/-2.6) with a non-significant change in CMRO(2) (+5.2%, +/-6.4). The coupling between CBF and CMRO(2) was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R(2) * is a promising approach for evaluating CBF and CMRO(2) changes in response to pharmacological interventions.
Caffeine induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated-BOLD fMRI study
Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B
Although functional MRI (fMRI) based on blood oxygenation-level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia calibrated-BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). In this study, we implemented a quantitative R2* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated-BOLD method, to examine the CBF and CMRO2 responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200mg caffeine dose. A dual echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, ±11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, ±2.9) and CMRO2 (+20.7%, ±1.4), and caffeine decreased CBF (-34.5%, ±2.6) with a non-significant change in CMRO2 (+5.2%, ±6.4). The coupling between CBF and CMRO2 was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated-BOLD methodology using R2* is a promising approach for evaluating CBF and CMRO2 changes in response to pharmacological interventions. PMID:18191583
Resting State Brain Function Analysis Using Concurrent BOLD in ASL Perfusion fMRI
Zhu, Senhua; Fang, Zhuo; Hu, Siyuan; Wang, Ze; Rao, Hengyi
The past decade has seen astounding discoveries about resting-state brain activity patterns in normal brain as well as their alterations in brain diseases. While the vast majority of resting-state studies are based on the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI), arterial spin labeling (ASL) perfusion fMRI can simultaneously capture BOLD and cerebral blood flow (CBF) signals, providing a unique opportunity for assessing resting brain functions with concurrent BOLD (ccBOLD) and CBF signals. Before taking that benefit, it is necessary to validate the utility of ccBOLD signal for resting-state analysis using conventional BOLD (cvBOLD) signal acquired without ASL modulations. To address this technical issue, resting cvBOLD and ASL perfusion MRI were acquired from a large cohort (n = 89) of healthy subjects. Four widely used resting-state brain function analyses were conducted and compared between the two types of BOLD signal, including the posterior cingulate cortex (PCC) seed-based functional connectivity (FC) analysis, independent component analysis (ICA), analysis of amplitude of low frequency fluctuation (ALFF), and analysis of regional homogeneity (ReHo). Consistent default mode network (DMN) as well as other resting-state networks (RSNs) were observed from cvBOLD and ccBOLD using PCC-FC analysis and ICA. ALFF from both modalities were the same for most of brain regions but were different in peripheral regions suffering from the susceptibility gradients induced signal drop. ReHo showed difference in many brain regions, likely reflecting the SNR and resolution differences between the two BOLD modalities. The DMN and auditory networks showed highest CBF values among all RSNs. These results demonstrated the feasibility of ASL perfusion MRI for assessing resting brain functions using its concurrent BOLD in addition to CBF signal, which provides a potentially useful way to maximize the utility of ASL perfusion MRI. PMID:23750275
BOLD fMRI in awake prairie voles: A platform for translational social and affective neuroscience.
Yee, J R; Kenkel, W M; Kulkarni, P; Moore, K; Perkeybile, A M; Toddes, S; Amacker, J A; Carter, C S; Ferris, C F
The advancement of neuroscience depends on continued improvement in methods and models. Here, we present novel techniques for the use of awake functional magnetic resonance imaging (fMRI) in the prairie vole (Microtus ochrogaster) - an important step forward in minimally-invasive measurement of neural activity in a non-traditional animal model. Imaging neural responses in prairie voles, a species studied for its propensity to form strong and selective social bonds, is expected to greatly advance our mechanistic understanding of complex social and affective processes. The use of ultra-high-field fMRI allows for recording changes in region-specific activity throughout the entire brain simultaneously and with high temporal and spatial resolutions. By imaging neural responses in awake animals, with minimal invasiveness, we are able to avoid the confound of anesthesia, broaden the scope of possible stimuli, and potentially make use of repeated scans from the same animals. These methods are made possible by the development of an annotated and segmented 3D vole brain atlas and software for image analysis. The use of these methods in the prairie vole provides an opportunity to broaden neuroscientific investigation of behavior via a comparative approach, which highlights the ethological relevance of pro-social behaviors shared between voles and humans, such as communal breeding, selective social bonds, social buffering of stress, and caregiving behaviors. Results using these methods show that fMRI in the prairie vole is capable of yielding robust blood oxygen level dependent (BOLD) signal changes in response to hypercapnic challenge (inhaled 5% CO2), region-specific physical challenge (unilateral whisker stimulation), and presentation of a set of novel odors. Complementary analyses of repeated restraint sessions in the imaging hardware suggest that voles do not require acclimation to this procedure. Taken together, awake vole fMRI represents a new arena of neurobiological
Two pitfalls of BOLD fMRI magnitude-based neuroimage analysis: non-negativity and edge effect.
Chen, Zikuan; Calhoun, Vince D
BOLD fMRI is accepted as a noninvasive imaging modality for neuroimaging and brain mapping. A BOLD fMRI dataset consists of magnitude and phase components. Currently, only the magnitude is used for neuroimage analysis. In this paper, we show that the fMRI-magnitude-based neuroimage analysis may suffer two pitfalls: one is that the magnitude is non-negative and cannot differentiate positive from negative BOLD activity; the other is an edge effect that may manifest as an edge enhancement or a spatial interior dip artifact at a local uniform BOLD region. We demonstrate these pitfalls via numeric simulations using a BOLD fMRI model and also via a phantom experiment. We also propose a solution by making use of the fMRI phase image, the counterpart of the fMRI magnitude.
Electrophysiological correlates of the BOLD signal for EEG-informed fMRI
Murta, Teresa; Leite, Marco; Carmichael, David W; Figueiredo, Patrícia; Lemieux, Louis
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. PMID:25277370
Electrophysiological correlates of the BOLD signal for EEG-informed fMRI.
Murta, Teresa; Leite, Marco; Carmichael, David W; Figueiredo, Patrícia; Lemieux, Louis
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG-fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological-haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG-fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG-fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG-fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations.
The relationship between time to peak of fMRI-BOLD responses and difficulty of a task suggests neuronal origins to the BOLD contrast
NASA Astrophysics Data System (ADS)
Alonso, Benito De Celis
Functional magnetic resonance imaging (fMRI) and its blood oxygen level contrast (BOLD) was used to study the response of the vibrissa system of rodents to different combinations of bilateral stimulations. We found that difficult tasks to perform, associated with longer neuronal periods, were correlated with larger times to peak (ttp) for the BOLD signal. This delay depended on number of vibrissa stimulated and the region of brain studied. By contrast, delay was not affected by which hemisphere was stimulated.
Studying the Spatial Distribution of Physiological Effects on BOLD Signals Using Ultrafast fMRI.
Tong, Yunjie; Frederick, Blaise Deb
The blood-oxygen-level dependent (BOLD) signal in functional MRI (fMRI) reflects both neuronal activations and global physiological fluctuations. These physiological fluctuations can be attributed to physiological low frequency oscillations (pLFOs), respiration, and cardiac pulsation. With typical TR values, i.e., 2 s or longer, the high frequency physiological signals (i.e., from respiration and cardiac pulsation) are aliased into the low frequency band, making it hard to study the individual effect of these physiological processes on BOLD. Recently developed multiband EPI sequences, which offer full brain coverage with extremely short TR values (400 ms or less) allow these physiological signals to be spectrally separated. In this study, we applied multiband resting state scans on nine healthy participants with TR = 0.4 s. The spatial distribution of each physiological process on BOLD fMRI was explored using their spectral features and independent component analysis (ICA). We found that the spatial distributions of different physiological processes are distinct. First, cardiac pulsation affects mostly the base of the brain, where high density of arteries exists. Second, respiration affects prefrontal and occipital areas, suggesting the motion associated with breathing might contribute to the noise. Finally, and most importantly, we found that the effects of pLFOs dominated many prominent ICA components, which suggests that, contrary to the popular belief that aliased cardiac and respiration signals are the main physiological noise source in BOLD fMRI, pLFOs may be the most influential physiological signals. Understanding and measuring these pLFOs are important for denoising and accurately modeling BOLD signals.
A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation
NASA Technical Reports Server (NTRS)
Strangman, Gary; Culver, Joseph P.; Thompson, John H.; Boas, David A.; Sutton, J. P. (Principal Investigator)
Near-infrared spectroscopy (NIRS) has been used to noninvasively monitor adult human brain function in a wide variety of tasks. While rough spatial correspondences with maps generated from functional magnetic resonance imaging (fMRI) have been found in such experiments, the amplitude correspondences between the two recording modalities have not been fully characterized. To do so, we simultaneously acquired NIRS and blood-oxygenation level-dependent (BOLD) fMRI data and compared Delta(1/BOLD) (approximately R(2)(*)) to changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations derived from the NIRS data from subjects performing a simple motor task. We expected the correlation with deoxyhemoglobin to be strongest, due to the causal relation between changes in deoxyhemoglobin concentrations and BOLD signal. Instead we found highly variable correlations, suggesting the need to account for individual subject differences in our NIRS calculations. We argue that the variability resulted from systematic errors associated with each of the signals, including: (1) partial volume errors due to focal concentration changes, (2) wavelength dependence of this partial volume effect, (3) tissue model errors, and (4) possible spatial incongruence between oxy- and deoxyhemoglobin concentration changes. After such effects were accounted for, strong correlations were found between fMRI changes and all optical measures, with oxyhemoglobin providing the strongest correlation. Importantly, this finding held even when including scalp, skull, and inactive brain tissue in the average BOLD signal. This may reflect, at least in part, the superior contrast-to-noise ratio for oxyhemoglobin relative to deoxyhemoglobin (from optical measurements), rather than physiology related to BOLD signal interpretation.
Pitfalls in Fractal Time Series Analysis: fMRI BOLD as an Exemplary Case
Eke, Andras; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Mukli, Peter; Nagy, Zoltan
This article will be positioned on our previous work demonstrating the importance of adhering to a carefully selected set of criteria when choosing the suitable method from those available ensuring its adequate performance when applied to real temporal signals, such as fMRI BOLD, to evaluate one important facet of their behavior, fractality. Earlier, we have reviewed on a range of monofractal tools and evaluated their performance. Given the advance in the fractal field, in this article we will discuss the most widely used implementations of multifractal analyses, too. Our recommended flowchart for the fractal characterization of spontaneous, low frequency fluctuations in fMRI BOLD will be used as the framework for this article to make certain that it will provide a hands-on experience for the reader in handling the perplexed issues of fractal analysis. The reason why this particular signal modality and its fractal analysis has been chosen was due to its high impact on today's neuroscience given it had powerfully emerged as a new way of interpreting the complex functioning of the brain (see "intrinsic activity"). The reader will first be presented with the basic concepts of mono and multifractal time series analyses, followed by some of the most relevant implementations, characterization by numerical approaches. The notion of the dichotomy of fractional Gaussian noise and fractional Brownian motion signal classes and their impact on fractal time series analyses will be thoroughly discussed as the central theme of our application strategy. Sources of pitfalls and way how to avoid them will be identified followed by a demonstration on fractal studies of fMRI BOLD taken from the literature and that of our own in an attempt to consolidate the best practice in fractal analysis of empirical fMRI BOLD signals mapped throughout the brain as an exemplary case of potentially wide interest. PMID:23227008
A model of neurovascular coupling and the BOLD response PART II.
Mathias, E J; Plank, M J; David, T
A mathematical model is developed which describes a signalling mechanism of neurovascular coupling with a model of a pyramidal neuron and its corresponding fMRI BOLD response. In the first part of two papers (Part I) we described the integration of the neurovascular coupling unit extended to include a complex neuron model, which includes the important Na/K ATPase pump, with a model that provides a BOLD signal taking its input from the cerebral blood flow and the metabolic rate of oxygen consumption. We showed that this produced a viable signal in terms of initial dip, positive and negative BOLD signals. In this paper (PART II) our model predicts the variations of the BOLD response due to variations in neuronal activity and indicates that the BOLD signal could be used as an initial biomarker for neuronal dysfunction or variations in the perfusion of blood to the cerebral tissue. We have compared the simulated hypoxic BOLD response to experimental BOLD signals observed in the hippocampus during hypoxia showing good agreement. This approach of combined quantitative modelling of neurovascular coupling response and its BOLD response will enable more specific assessment of a brain region.
Arterial spin labeling versus BOLD in direct challenge and drug-task interaction pharmacological fMRI.
Stewart, Stephanie B; Koller, Jonathan M; Campbell, Meghan C; Black, Kevin J
A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease. The study compared the effect of drug directly or the interaction of the drug with a cognitive task. Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to the cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.
Eyeblink classical conditioning and BOLD fMRI of anesthesia-induced changes in the developing brain.
Aksenov, Daniil P; Miller, Michael J; Li, Limin; Wyrwicz, Alice M
Millions of children undergo general anesthesia each year in the USA alone, and a growing body of literature from animals and humans suggests that exposure to anesthesia at an early age can impact neuronal development, leading to learning and memory impairments later in childhood. Although a number of studies have reported behavioral and structural effects of anesthesia exposure during infancy, the functional manifestation of these changes has not been previous examined. In this study we used BOLD fMRI to measure the functional response to stimulation in the whisker barrel cortex of awake rabbits before and after learning a trace eyeblink classical conditioning paradigm. The functional changes, in terms of activated volume and time course, in rabbits exposed to isoflurane anesthesia during infancy was compared to unanesthetized controls when both groups reached young adulthood. Our findings show that whereas both groups exhibited decreased BOLD response duration after learning, the anesthesia-exposed group also showed a decrease in BOLD response volume in the whisker barrel cortex, particularly in the deeper infragranular layer. These results suggest that anesthesia exposure during infancy may affect the intracortical processes that mediate learning-related plasticity.
Resting state BOLD fMRI for pre-surgical planning
Kamran, Mudassar; Hacker, Carl D; Allen, Monica G; Mitchell, Timothy J; Leuthardt, Eric C; Snyder, Abraham Z; Shimony, Joshua S
SYNOPSIS Resting state functional MRI (rsfMRI) measures spontaneous fluctuations in the BOLD signal and can be used to elucidate the brain's functional organization. It can be used to simultaneously assess multiple distributed resting state networks. Unlike task fMRI, rsfMRI does not require task performance and thus can be performed in any subject that can obtain an MRI scan. In this article we present a brief introduction of rsfMRI processing methods followed by a detailed discussion on the use of rsfMRI in pre-surgical planning. Example cases are provided to highlight the strengths and limitations of the technique. PMID:25441506
Repeated BOLD-fMRI Imaging of Deep Brain Stimulation Responses in Rats
Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung
Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464
Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7 T.
Huber, Laurentius; Goense, Jozien; Kennerley, Aneurin J; Ivanov, Dimo; Krieger, Steffen N; Lepsien, Jöran; Trampel, Robert; Turner, Robert; Möller, Harald E
Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in 'arterial' and 'venous' blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between 'arterial' and 'venous' contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms.
Influence of BOLD Contributions to Diffusion fMRI Activation of the Visual Cortex
Williams, Rebecca J.; Reutens, David C.; Hocking, Julia
Reliance on the hemodynamic response as a surrogate marker of neural activity imposes an intrinsic limit on the spatial specificity of functional MRI. An alternative approach based on diffusion-weighted functional MRI (DfMRI) has been reported as a contrast less reliant on hemodynamic effects, however current evidence suggests that both hemodynamic and unique neural sources contribute to the diffusion signal. Here we compare activation patterns obtained with the standard blood oxygenation level-dependent (BOLD) contrast to DfMRI in order to gain a deeper understanding of how the BOLD proportion contributes to the observable diffusion signal. Both individual and group-level activation patterns obtained with DfMRI and BOLD to a visual field stimulation paradigm were analyzed. At the individual level, the DfMRI contrast showed a strong, positive relationship between the volumes of cortex activated in response to quadrant- and hemi-field visual stimulation. This was not observed in the corresponding BOLD experiment. Overall, the DfMRI response indicated less between-subject variability, with random effects analyses demonstrating higher statistical values at the peak voxel for DfMRI. Furthermore, the spatial extent of the activation was more restricted to the primary visual region for DfMRI than BOLD. However, the diffusion signal was sensitive to the hemodynamic response in a manner dependent on experimental manipulation. It was also limited by its low signal-to-noise ratio (SNR), demonstrating lower sensitivity than BOLD. Together these findings both support DfMRI as a contrast that bears a closer spatial relationship to the underlying neural activity than BOLD, and raise important caveats regarding its utilization. Models explaining the DfMRI signal change need to consider the dynamic vascular contributions that may vary with neural activity. PMID:27445654
MDMA (Ecstasy) association with impaired fMRI BOLD thalamic coherence and functional connectivity*
Salomon, Ronald M.; Karageorgiou, John; Dietrich, Mary S.; McLellan, Jessica Y.; Charboneau, Evonne J.; Blackford, Jennifer U.; Cowan, Ronald L.
Background MDMA exposure is associated with chronic serotonergic dysfunction in preclinical and clinical studies. A recent functional magnetic resonance imaging (fMRI) comparison of past MDMA users to non-MDMA-using controls revealed increased spatial extent and amplitude of activation in the supplementary motor area during motor tasks (Karageorgiou et al., 2009). Blood oxygenation level dependent (BOLD) data from that study were reanalyzed for intraregional coherence and for inter-regional temporal correlations between time series, as functional connectivity. Methods Fourteen MDMA users and ten controls reporting similar non-MDMA abuse performed finger taps during fMRI. Fourteen motor pathway regions plus a pontine raphé region were examined. Coherence was expressed as percent of voxels positively correlated with an intraregional index voxel. Functional connectivity was determined using wavelet correlations. Results Intraregional thalamic coherence was significantly diminished at low frequencies in MDMA users compared to controls (p=0.009). Inter-regional functional connectivity was significantly weaker for right thalamo - left caudate (p=0.002), right thalamo - left thalamus (p=0.007), right caudate - right postcentral (p=0.007) and right supplementary motor area - right precentral gyrus (p=0.011) region pairs compared to controls. When stratified by lifetime exposure, significant negative associations were observed between cumulative MDMA use and functional connectivity in seven other region-pairs, while only one region-pair showed a positive association. Conclusions Reported prior MDMA use was associated with deficits in BOLD intraregional coherence and inter-regional functional connectivity, even among functionally robust pathways involving motor regions. This suggests that MDMA use is associated with long-lasting effects on brain neurophysiology beyond the cognitive domain. PMID:21807471
Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.
Liang, Christine L; Ances, Beau M; Perthen, Joanna E; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T; Hopkins, Susan R; Buxton, Richard B
The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes.
A component based noise correction method (CompCor) for BOLD and perfusion based fMRI.
Behzadi, Yashar; Restom, Khaled; Liau, Joy; Liu, Thomas T
A component based method (CompCor) for the reduction of noise in both blood oxygenation level-dependent (BOLD) and perfusion-based functional magnetic resonance imaging (fMRI) data is presented. In the proposed method, significant principal components are derived from noise regions-of-interest (ROI) in which the time series data are unlikely to be modulated by neural activity. These components are then included as nuisance parameters within general linear models for BOLD and perfusion-based fMRI time series data. Two approaches for the determination of the noise ROI are considered. The first method uses high-resolution anatomical data to define a region of interest composed primarily of white matter and cerebrospinal fluid, while the second method defines a region based upon the temporal standard deviation of the time series data. With the application of CompCor, the temporal standard deviation of resting-state perfusion and BOLD data in gray matter regions was significantly reduced as compared to either no correction or the application of a previously described retrospective image based correction scheme (RETROICOR). For both functional perfusion and BOLD data, the application of CompCor significantly increased the number of activated voxels as compared to no correction. In addition, for functional BOLD data, there were significantly more activated voxels detected with CompCor as compared to RETROICOR. In comparison to RETROICOR, CompCor has the advantage of not requiring external monitoring of physiological fluctuations.
Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism: An EEG Power and BOLD fMRI Investigation
Hames, Elizabeth' C.; Murphy, Brandi; Rajmohan, Ravi; Anderson, Ronald C.; Baker, Mary; Zupancic, Stephen; O'Boyle, Michael; Richman, David
Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20–28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs. PMID:27148020
Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism: An EEG Power and BOLD fMRI Investigation.
Hames, Elizabeth' C; Murphy, Brandi; Rajmohan, Ravi; Anderson, Ronald C; Baker, Mary; Zupancic, Stephen; O'Boyle, Michael; Richman, David
Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20-28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs.
How and when the fMRI BOLD signal relates to underlying neural activity: The danger in dissociation
Ekstrom, Arne
Functional magnetic resonance imaging (fMRI) has become the dominant means of measuring behavior-related neural activity in the human brain. Yet the relation between the blood oxygen-level dependent (BOLD) signal and underlying neural activity remains an open and actively researched question. A widely accepted model, established for sensory neo-cortex, suggests that the BOLD signal reflects peri-synaptic activity in the form of the local field potential rather than the spiking rate of individual neurons. Several recent experimental results, however, suggest situations in which BOLD, spiking, and the local field potential dissociate. Two different models are discussed, based on the literature reviewed to account for this dissociation, a circuitry-based and vascular-based explanation. Both models are found to account for existing data under some testing situations and in certain brain regions. Because both the vascular and local circuitry-based explanations challenge the BOLD-LFP coupling model, these models provide guidance in predicting when BOLD can be expected to reflect neural processing and when the underlying relation with BOLD may be more complex than a direct correspondence. PMID:20026191
A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series
Demanuele, Charmaine; Bähner, Florian; Plichta, Michael M.; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas; Durstewitz, Daniel
Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze (RAM) task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in
A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series.
Demanuele, Charmaine; Bähner, Florian; Plichta, Michael M; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas; Durstewitz, Daniel
Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze (RAM) task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in
Spatio-Temporal Information Analysis of Event-Related BOLD Responses
Alpert, Galit Fuhrmann; Handwerker, Dan; Sun, Felice T.; D'Esposito, Mark; Knight, Robert T.
A new approach for analysis of event related fMRI (BOLD) signals is proposed. The technique is based on measures from information theory and is used both for spatial localization of task related activity, as well as for extracting temporal information regarding the task dependent propagation of activation across different brain regions. This approach enables whole brain visualization of voxels (areas) most involved in coding of a specific task condition, the time at which they are most informative about the condition, as well as their average amplitude at that preferred time. The approach does not require prior assumptions about the shape of the hemodynamic response function (HRF), nor about linear relations between BOLD response and presented stimuli (or task conditions). We show that relative delays between different brain regions can also be computed without prior knowledge of the experimental design, suggesting a general method that could be applied for analysis of differential time delays that occur during natural, uncontrolled conditions. Here we analyze BOLD signals recorded during performance of a motor learning task. We show that during motor learning, the BOLD response of unimodal motor cortical areas precedes the response in higher-order multimodal association areas, including posterior parietal cortex. Brain areas found to be associated with reduced activity during motor learning, predominantly in prefrontal brain regions, are informative about the task typically at significantly later times. PMID:17188515
Functional dissociation of transient and sustained fMRI BOLD components in human auditory cortex revealed with a streaming paradigm based on interaural time differences.
Schadwinkel, Stefan; Gutschalk, Alexander
A number of physiological studies suggest that feature-selective adaptation is relevant to the pre-processing for auditory streaming, the perceptual separation of overlapping sound sources. Most of these studies are focused on spectral differences between streams, which are considered most important for streaming. However, spatial cues also support streaming, alone or in combination with spectral cues, but physiological studies of spatial cues for streaming remain scarce. Here, we investigate whether the tuning of selective adaptation for interaural time differences (ITD) coincides with the range where streaming perception is observed. FMRI activation that has been shown to adapt depending on the repetition rate was studied with a streaming paradigm where two tones were differently lateralized by ITD. Listeners were presented with five different ΔITD conditions (62.5, 125, 187.5, 343.75, or 687.5 μs) out of an active baseline with no ΔITD during fMRI. The results showed reduced adaptation for conditions with ΔITD ≥ 125 μs, reflected by enhanced sustained BOLD activity. The percentage of streaming perception for these stimuli increased from approximately 20% for ΔITD = 62.5 μs to > 60% for ΔITD = 125 μs. No further sustained BOLD enhancement was observed when the ΔITD was increased beyond ΔITD = 125 μs, whereas the streaming probability continued to increase up to 90% for ΔITD = 687.5 μs. Conversely, the transient BOLD response, at the transition from baseline to ΔITD blocks, increased most prominently as ΔITD was increased from 187.5 to 343.75 μs. These results demonstrate a clear dissociation of transient and sustained components of the BOLD activity in auditory cortex.
Hippocampal CA3 activation alleviates fMRI-BOLD responses in the rat prefrontal cortex induced by electrical VTA stimulation
Scherf, Thomas
Functional magnetic resonance imaging (fMRI) was used to identify brain- wide networks that are activated by electrical stimulation of either the ventral tegmental area (VTA) or hippocampal CA3 region. Stimulation of either one of these regions caused significant BOLD responses in common structures, such as the septum and left and right hippocampus, but also in unique structures, such as the medial prefrontal cortex region/anterior cingulum region (mPFC/ACC) and striatum, which were only activated during VTA stimulation. Concurrent stimulations of the two structures resulted in no additive BOLD responses but significantly reduced BOLD responses in the mPFC/ACC when compared with sole VTA stimulation. This reduction is caused by costimulation of the hippocampal CA3 region, which was itself not sufficient to modify BOLD signal intensities in the mPFC/ACC. Under this experimental condition, functional connectivity between VTA and mPFC/ACC in terms of neurophysiological interactions was causative, driven by direct electrical stimulation of VTA projecting neurons, the resulting functional connectivity in terms of correlated BOLD time series becoming masked as soon as hippocampal projections concurrently coactivated mPFC neurons. This result warns against misinterpretation of the absence of functional connectivity in fMRI data sets, because strong existing neurophysiological interactions can be obscured by unrelated network activities. PMID:28241047
fMRI bold signal analysis using a novel nonparametric statistical method
NASA Astrophysics Data System (ADS)
De Mazière, Patrick A.; Van Hulle, Marc M.
We present in this article a novel analytical method that enables the application of nonparametric rank-order statistics to fMRI data analysis, since it takes the omnipresent serial correlations (temporal autocorrelations) properly into account. Comparative simulations, using the common General Linear Model and the permutation test, confirm the validity and usefulness of our approach. Our simulations, which are performed with both synthetic and real fMRI data, show that our method requires significantly less computation time than permutation-based methods, while offering the same order of robustness and returning more information about the evoked response when combined with/compared to the results obtained with the common General Lineal Model approach.
Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD
Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge
Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543
PHYCAA+: an optimized, adaptive procedure for measuring and controlling physiological noise in BOLD fMRI.
Churchill, Nathan W; Strother, Stephen C
The presence of physiological noise in functional MRI can greatly limit the sensitivity and accuracy of BOLD signal measurements, and produce significant false positives. There are two main types of physiological confounds: (1) high-variance signal in non-neuronal tissues of the brain including vascular tracts, sinuses and ventricles, and (2) physiological noise components which extend into gray matter tissue. These physiological effects may also be partially coupled with stimuli (and thus the BOLD response). To address these issues, we have developed PHYCAA+, a significantly improved version of the PHYCAA algorithm (Churchill et al., 2011) that (1) down-weights the variance of voxels in probable non-neuronal tissue, and (2) identifies the multivariate physiological noise subspace in gray matter that is linked to non-neuronal tissue. This model estimates physiological noise directly from EPI data, without requiring external measures of heartbeat and respiration, or manual selection of physiological components. The PHYCAA+ model significantly improves the prediction accuracy and reproducibility of single-subject analyses, compared to PHYCAA and a number of commonly-used physiological correction algorithms. Individual subject denoising with PHYCAA+ is independently validated by showing that it consistently increased between-subject activation overlap, and minimized false-positive signal in non gray-matter loci. The results are demonstrated for both block and fast single-event task designs, applied to standard univariate and adaptive multivariate analysis models.
BOLD fMRI integration into radiosurgery treatment planning of cerebral vascular malformations
Stancanello, Joseph; Cavedon, Carlo; Francescon, Paolo; Causin, Francesco; Avanzo, Michele; Colombo, Federico; Cerveri, Pietro; Ferrigno, Giancarlo; Uggeri, Fulvio
Functional magnetic resonance imaging (fMRI) is used to distinguish areas of the brain responsible for different tasks and functions. It is possible, for example, by using fMRI images, to identify particular regions in the brain which can be considered as 'functional organs at risk' (fOARs), i.e., regions which would cause significant patient morbidity if compromised. The aim of this study is to propose and validate a method to exploit functional information for the identification of fOARs in CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery treatment planning; in particular, given the high spatial accuracy offered by the CyberKnife system, local nonrigid registration is used to reach accurate image matching. Five patients affected by arteriovenous malformations (AVMs) and scheduled to undergo radiosurgery were scanned prior to treatment using computed tomography (CT), three-dimensional (3D) rotational angiography (3DRA), T2 weighted and blood oxygenation level dependent echo planar imaging MRI. Tasks were chosen on the basis of lesion location by considering those areas which could be potentially close to treatment targets. Functional data were superimposed on 3DRA and CT used for treatment planning. The procedure for the localization of fMRI areas was validated by direct cortical stimulation on 38 AVM and tumor patients undergoing conventional surgery. Treatment plans studied with and without considering fOARs were significantly different, in particular with respect to both maximum dose and dose volume histograms; consideration of the fOARs allowed quality indices of treatment plans to remain almost constant or to improve in four out of five cases compared to plans with no consideration of fOARs. In conclusion, the presented method provides an accurate tool for the integration of functional information into AVM radiosurgery, which might help to minimize undesirable side effects and to make radiosurgery less invasive.
Spatiotemporal properties of the BOLD response in the songbirds' auditory circuit during a variety of listening tasks.
Van Meir, Vincent; Boumans, Tiny; De Groof, Geert; Van Audekerke, Johan; Smolders, Alain; Scheunders, Paul; Sijbers, Jan; Verhoye, Marleen; Balthazart, Jacques; Van der Linden, Annemie
Auditory fMRI in humans has recently received increasing attention from cognitive neuroscientists as a tool to understand mental processing of learned acoustic sequences and analyzing speech recognition and development of musical skills. The present study introduces this tool in a well-documented animal model for vocal learning, the songbird, and provides fundamental insight in the main technical issues associated with auditory fMRI in these songbirds. Stimulation protocols with various listening tasks lead to appropriate activation of successive relays in the songbirds' auditory pathway. The elicited BOLD response is also region and stimulus specific, and its temporal aspects provide accurate measures of the changes in brain physiology induced by the acoustic stimuli. Extensive repetition of an identical stimulus does not lead to habituation of the response in the primary or secondary telencephalic auditory regions of anesthetized subjects. The BOLD signal intensity changes during a stimulation and subsequent rest period have a very specific time course which shows a remarkable resemblance to auditory evoked BOLD responses commonly observed in human subjects. This observation indicates that auditory fMRI in the songbird may establish a link between auditory related neuro-imaging studies done in humans and the large body of neuro-ethological research on song learning and neuro-plasticity performed in songbirds.
Fourier modeling of the BOLD response to a breath-hold task: Optimization and reproducibility.
Pinto, Joana; Jorge, João; Sousa, Inês; Vilela, Pedro; Figueiredo, Patrícia
Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order to maintain a steady supply of brain perfusion, and it may provide a sensitive disease biomarker. Measurement of the blood oxygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best modeling approach for the accurate quantification of CVR maps remains an open issue. Here, we compare and optimize Fourier models of the BOLD response to a BH task with a preparatory inspiration, and assess the test-retest reproducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI sessions. Linear combinations of sine-cosine pairs at the BH task frequency and its successive harmonics were added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of determination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels exhibiting significant BOLD responses, the estimated CVR values, and their test-retest reproducibility. The brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also yielded the best test-retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set consisting of a sine-cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD-fMRI CVR measurements
Detecting static and dynamic differences between eyes-closed and eyes-open resting states using ASL and BOLD fMRI.
Zou, Qihong; Yuan, Bin-Ke; Gu, Hong; Liu, Dongqiang; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong; Zang, Yu-Feng
Resting-state fMRI studies have increasingly focused on multi-contrast techniques, such as BOLD and ASL imaging. However, these techniques may reveal different aspects of brain activity (e.g., static vs. dynamic), and little is known about the similarity or disparity of these techniques in detecting resting-state brain activity. It is therefore important to assess the static and dynamic characteristics of these fMRI techniques to guide future applications. Here we acquired fMRI data while subjects were in eyes-closed (EC) and eyes-open (EO) states, using both ASL and BOLD techniques, at two research centers (NIDA and HNU). Static brain activity was calculated as voxel-wise mean cerebral blood flow (CBF) using ASL, i.e., CBF-mean, while dynamic activity was measured by the amplitude of low frequency fluctuations (ALFF) of BOLD, i.e., BOLD-ALFF, at both NIDA and HNU, and CBF, i.e., CBF-ALFF, at NIDA. We showed that mean CBF was lower under EC than EO in the primary visual cortex, while BOLD-ALFF was higher under EC in the primary somatosensory cortices extending to the primary auditory cortices and lower in the lateral occipital area. Interestingly, mean CBF and BOLD-ALFF results overlapped at the visual cortex to a very small degree. Importantly, these findings were largely replicated by the HNU dataset. State differences found by CBF-ALFF were located in the primary auditory cortices, which were generally a subset of BOLD-ALFF and showed no spatial overlap with CBF-mean. In conclusion, static brain activity measured by mean CBF and dynamic brain activity measured by BOLD- and CBF-ALFF may reflect different aspects of resting-state brain activity and a combination of ASL and BOLD may provide complementary information on the biophysical and physiological processes of the brain.
Lack of generalizability of sex differences in the fMRI BOLD activity associated with language processing in adults
Ihnen, S. K. Z.; Church, Jessica A.; Petersen, Steven E.; Schlaggar, Bradley L.
A lack of consensus exists as to whether there are sex differences in the fMRI BOLD signal correlates of language processing in the human brain. Here, whole-brain fMRI was used to examine the neural activity of 46 adults performing one of two sets of language tasks. Conservative quantitative and qualitative criteria identified a handful of statistically significant regions of "sex difference" within each task separately. When each of the two sets of regions was investigated in the group of subjects performing the other task set, however, most of the identified "sex differences" failed to generalize. Identical analyses of the same subjects divided into sex-matched pseudorandom control groups for each task set separately revealed that it is possible to observe a similar number of statistically significant regions of "group difference" in the task-associated BOLD signal, even when the groups do not differ on any of the measured behavioral parameters, or any obvious demographic characteristic. Together, these results suggest that one should be cautious when interpreting studies that purport to have identified regions of difference between groups, whether those groups are divided by sex or by any other criterion. In particular, generalization or replication of a result in independent data sets is necessary for establishing conclusive support for any hypothesis about differences in brain function between groups. PMID:19162200
A model of neurovascular coupling and the BOLD response: PART I.
Mathias, E J; Plank, M J; David, T
The mechanisms with which neurons communicate with the vasculature to increase blood flow, termed neurovascular coupling is still unclear primarily due to the complex interactions between many parameters and the difficulty in accessing, monitoring and measuring them in the highly heterogeneous brain. Hence a solid theoretical framework based on existing experimental knowledge is necessary to study the relation between neural activity, the associated vasoactive factors released and their effects on the vasculature. Such a framework should also be related to experimental data so that it can be validated against repetitive experiments and generate verifiable hypothesis. We have developed a mathematical model which describes a signaling mechanism of neurovascular coupling with a model of pyramidal neuron and its corresponding fMRI BOLD response. In the first part of two papers we describe the integration of the neurovascular coupling unit extended to include a complex neuron model, which includes the important Na/K ATPase pump, with a model that provides a BOLD signal taking its input from the cerebral blood flow and the metabolic rate of oxygen consumption. We show that this produces a viable signal in terms of initial dip, positive and negative BOLD signals.
All that glitters is not BOLD: inconsistencies in functional MRI
NASA Astrophysics Data System (ADS)
Renvall, Ville; Nangini, Cathy; Hari, Riitta
The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is a widely-accepted marker of brain activity. The acquisition parameters (APs) of fMRI aim at maximizing the signals related to neuronal activity while minimizing unrelated signal fluctuations. Currently, a diverse set of APs is used to acquire BOLD fMRI data. Here we demonstrate that some fMRI responses are alarmingly inconsistent across APs, ranging from positive to negative, or disappearing entirely, under identical stimulus conditions. These discrepancies, resulting from non-BOLD effects masquerading as BOLD signals, have remained largely unnoticed because studies rarely employ more than one set of APs. We identified and characterized non-BOLD responses in several brain areas, including posterior cingulate cortex and precuneus, as well as AP-dependence of both the signal time courses and of seed-based functional networks, noticing that AP manipulation can inform about the origin of the measured signals.
Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.
Liu, Xiaolin; Lauer, Kathryn K; Douglas Ward, B; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R; Li, Shi-Jiang; Hudetz, Anthony G
Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.
EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal
Sclocco, Roberta; Tana, Maria G.; Visani, Elisa; Gilioli, Isabella; Panzica, Ferruccio; Franceschetti, Silvana; Cerutti, Sergio; Bianchi, Anna M.
In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neural activity, rather than with absolute power. Concurrently, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be also important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between the two signals. Here we propose a method to perform EEG-informed fMRI analysis where the changes in the spectral profile are modeled, and, at the same time, the distinction between rhythms is preserved. We compared our model with two other frequency-dependent regressors modeling using simultaneous EEG-fMRI data from healthy subjects performing a motor task. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related, well localized activated volumes. Furthermore, we showed that including among the regressors also EEG rhythms not primarily involved in the task enhances the performance of the analysis, even when only correlations with BOLD signal and specific EEG rhythms are explored. PMID:24744720
Dependence of the negative BOLD response on somatosensory stimulus intensity.
Klingner, Carsten M; Hasler, Caroline; Brodoehl, Stefan; Witte, Otto W
The primary somatosensory cortex (SI) has been shown to encode the intensity of a stimulus applied to the contralateral side of the body. Recent studies have demonstrated that ipsilateral SI is also involved in the processing of somatosensory information. In this study, we investigated the dependence of the negative BOLD response in ipsilateral SI on the intensity of somatosensory stimulation. Functional MRI was performed in 12 healthy subjects during electrical median nerve stimulation at four different intensities. A monotonic relationship between stimulus intensity and the strength of the negative BOLD response in ipsilateral SI was found. Additionally, a psychophysiological experiment revealed tight coupling between the stimulus intensity applied to one hand and increased perceptual threshold of the other hand. These findings indicate a stimulus intensity-dependent inhibition of ipsilateral SI.
CBF/CMRO2 Coupling Measured with Calibrated-BOLD fMRI: Sources of Bias
Leontiev, Oleg; Dubowitz, David J.; Buxton, Richard B.
The coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index n, the ratio of fractional CBF changes to fractional CMRO2 changes. Measurements of n have yielded varying results, and it is not known if the observed variability is due to measurement techniques or underlying physiology. The calibrated BOLD approach using hypercapnia offers a promising tool for assessing changes in CBF/CMRO2 coupling in health and disease, but potential systematic errors have not yet been characterized. The goal of this study was to experimentally evaluate the magnitude of bias in the estimate of n that arises from the way in which a region of interest (ROI) is chosen for averaging data, and to relate this potential bias to a more general theoretical consideration of the sources of systematic errors in the calibrated BOLD experiment. Results were compared for different approaches for defining an ROI within the visual cortex based on: 1) retinotopically-defined V1; 2) a functional CBF localizer; and 3) a functional BOLD localizer. Data in V1 yielded a significantly lower estimate of n (2.45) compared to either CBF (n = 3.45) or BOLD (n = 3.18) localizers. Different statistical thresholds produced biases in estimates of n with values ranging from 3.01 (low threshold) to 4.37 (high threshold). Possible sources of the observed biases are discussed. These results underscore the importance of a critical evaluation of the methodology, and the adoption of consistent standards for applying the calibrated BOLD approach to the evaluation of CBF/CMRO2 coupling. PMID:17524665
CBF/CMRO2 coupling measured with calibrated BOLD fMRI: sources of bias.
Leontiev, Oleg; Dubowitz, David J; Buxton, Richard B
The coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index n, the ratio of fractional CBF changes to fractional CMRO2 changes. Measurements of n have yielded varying results, and it is not known if the observed variability is due to measurement techniques or underlying physiology. The calibrated BOLD approach using hypercapnia offers a promising tool for assessing changes in CBF/CMRO2 coupling in health and disease, but potential systematic errors have not yet been characterized. The goal of this study was to experimentally evaluate the magnitude of bias in the estimate of n that arises from the way in which a region of interest (ROI) is chosen for averaging data and to relate this potential bias to a more general theoretical consideration of the sources of systematic errors in the calibrated BOLD experiment. Results were compared for different approaches for defining an ROI within the visual cortex based on: (1) retinotopically defined V1; (2) a functional CBF localizer; and (3) a functional BOLD localizer. Data in V1 yielded a significantly lower estimate of n (2.45) compared to either CBF (n=3.45) or BOLD (n=3.18) localizers. Different statistical thresholds produced biases in estimates of n with values ranging from 3.01 (low threshold) to 4.37 (high threshold). Possible sources of the observed biases are discussed. These results underscore the importance of a critical evaluation of the methodology, and the adoption of consistent standards for applying the calibrated BOLD approach to the evaluation of CBF/CMRO2 coupling.
Influence of gradient acoustic noise on fMRI response in the human visual cortex.
Zhang, Nanyin; Zhu, Xiao-Hong; Chen, Wei
A paired-stimuli paradigm combined with fMRI was utilized to study the effect of gradient acoustic noise on fMRI response in the human primary visual cortex (V1) in terms of the auditory-visual cross-modal neural interaction. The gradient noise generated during the fMRI acquisition was used as the primary stimulus, and a single flashing light was used as the secondary stimulus. An interstimulus interval (ISI) separated the two. Six tasks were designed with different ISIs ranging from 50 to 700 ms. Both BOLD signal intensity and the number of activated pixels in V1 were analyzed and examined, and they showed a significant reduction when the gradient noise preceded the flashing light by approximately 300 ms. These results indicate that the gradient acoustic noise generated during fMRI acquisitions does interfere with neural behavior and the BOLD signal in the human visual cortex. This interference is modulated by the delay between the gradient noise and visual stimulation, and it can be studied quantitatively when the stimulation paradigm is designed appropriately. This study provides evidence of the auditory-visual interaction during fMRI studies, and the results should have an impact on fMRI applications.
BOLD Response to Semantic and Syntactic Processing during Hypoglycemia Is Load-Dependent
ERIC Educational Resources Information Center
Schafer, Robin J.; Page, Kathleen A.; Arora, Jagriti; Sherwin, Robert; Constable, R. Todd
This study investigates how syntactic and semantic load factors impact sentence comprehension and BOLD signal under moderate hypoglycemia. A dual session, whole brain fMRI study was conducted on 16 healthy participants using the glucose clamp technique. In one session, they experienced insulin-induced hypoglycemia (plasma glucose at [image…
Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: Implications for BOLD-fMRI
Ances, Beau M.; Leontiev, Oleg; Perthen, Joanna E.; Liang, Christine; Lansing, Amy E.; Buxton, Richard B.
Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO2). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (∼5.8%), differences in n (2.21±0.03 in VC and 1.58±0.03 in LN; Cohen d=1.71) produced substantially weaker (∼3.7×) subcortical than cortical BOLD responses relative to CMRO2 changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and sub-cortical regions. PMID:18164629
Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI.
Ances, Beau M; Leontiev, Oleg; Perthen, Joanna E; Liang, Christine; Lansing, Amy E; Buxton, Richard B
Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.
Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis
Castaldi, E.; Cicchini, G. M.; Cinelli, L.; Rizzo, S.; Morrone, M. C.
Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation. PMID:27780207
Dynamic Retrospective Filtering of Physiological Noise in BOLD fMRI: DRIFTER
Särkkä, Simo; Solin, Arno; Nummenmaa, Aapo; Vehtari, Aki; Auranen, Toni; Vanni, Simo; Lin, Fa-Hsuan
In this article we introduce the DRIFTER algorithm, which is a new model based Bayesian method for retrospective elimination of physiological noise from functional magnetic resonance imaging (fMRI) data. In the method, we first estimate the frequency trajectories of the physiological signals with the interacting multiple models (IMM) filter algorithm. The frequency trajectories can be estimated from external reference signals, or if the temporal resolution is high enough, from the fMRI data. The estimated frequency trajectories are then used in a state space model in combination of a Kalman filter (KF) and Rauch-Tung-Striebel (RTS) smoother, which separates the signal into an activation related cleaned signal, physiological noise, and white measurement noise components. Using experimental data, we show that the method outperforms the RETROICOR algorithm if the shape and amplitude of the physiological signals change over time. PMID:22281675
Acute Alcohol Effects on Contextual Memory BOLD Response: Differences Based on Fragmentary Blackout History
Wetherill, Reagan R.; Schnyer, David M.; Fromme, Kim
Background Contextual memory, or memory for source details, is an important aspect of episodic memory and has been implicated in alcohol-induced fragmentary blackouts (FB). Little is known, however, about how neural functioning during contextual memory processes may differ between individuals with and without a history of fragmentary blackouts. This study examined whether neural activation during a contextual memory task differed by history of fragmentary blackout and acute alcohol consumption. Methods Twenty-four matched individuals with (FB+; n = 12) and without (FB−; n = 12) a history of FBs were recruited from a longitudinal study of alcohol use and behavioral risks and completed a laboratory beverage challenge followed by two functional magnetic resonance imaging (fMRI) sessions under no alcohol and alcohol [breath alcohol concentration (BrAC) = 0.08%] conditions. Task performance and brain hemodynamic activity during a block design contextual memory task were examined across 48 fMRI sessions. Results Groups demonstrated no differences in performance on the contextual memory task, yet exhibited different brain response patterns after alcohol intoxication. A significant FB group by beverage interaction emerged in bilateral dorsolateral prefrontal cortex and posterior parietal cortex with FB− individuals showing greater BOLD response after alcohol exposure (p < .05). Conclusions Alcohol had differential effects on neural activity for FB+ and FB− individuals during recollection of contextual information, perhaps suggesting a neurobiological mechanism associated with alcohol-induced fragmentary blackouts. PMID:22420742
Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology.
Bentley, William J; Li, Jingfeng M; Snyder, Abraham Z; Raichle, Marcus E; Snyder, Lawrence H
The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these "task-negative" BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process.
Reproducibility of hypocapnic cerebrovascular reactivity measurements using BOLD fMRI in combination with a paced deep breathing task.
Sousa, I; Vilela, P; Figueiredo, P
It has recently been proposed that hypocapnic cerebrovascular reactivity (CVR) can be assessed by measuring the blood oxygenation level dependent (BOLD) response to paced deep breathing (PDB) tasks inducing mild hypocapnia and vasoconstriction. In this work, we aim to assess the test-retest reproducibility and inter-subject variability of BOLD CVR measurements obtained using a PDB task and different methods to analyse the associated BOLD signal. The respiratory protocol consisted of alternating 40s of PDB with normal free breathing; expired CO2 pressure levels (PETCO2) were continuously monitored. CVR was quantified using either a timecourse curve analysis (TCA) approach, where the magnitude of response peaks is emphasized, or general linear modelling (GLM) including optimisation of the BOLD response latencies. The GLM fit was carried out using two types of response regressors: one that was computed as the convolution of PETCO2 traces with a gamma function and another that consisted of the convolution of PDB paradigm blocks with a physiological model of the respiratory response. Haemodynamic response latencies were optimised either on a voxel basis or for the whole imaging region. We found that the GLM method based on PDB task or PETCO2 traces and voxelwise optimisation of response latencies provided the most reproducible measures of CVR. For the average grey matter CVR, the inter-subject coefficient of variation (CVinter) / intra-subject coefficient of variation (CVintra) / intra-class correlation coefficient (ICC) were 20%/8%/0.8 and 27%/8%/0.9, using the task and PETCO2 timecourses, respectively. In terms of the spatial reproducibility, the group mean (±standard deviation) of the spatial ICC (ICCspatial) was 1.04±0.23 and 1.02±0.26, for the task and PETCO2 timecourses, respectively. These results indicate generally good reproducibility of the hypocapnic CVR maps obtained using the proposed PDB task and analysis methodology. This suggests that such protocol
BOLD Responses to Stimuli: Dependence on Frequency, Stimulus form, Amplitude, and Repetition Rate.
NASA Astrophysics Data System (ADS)
Robinson, Peter; Drysdale, Peter; van der Merwe, Helena; Kyriakou, Elizabeth; Rigozzi, Michelle; Germanoska, Biljana; Rennie, Christopher
A quantitative theory is developed for the relationship between stimulus and the resulting Blood Oxygen Level Dependent (BOLD) functional MRI signal in the brain. The relationship of stimuli to neuronal activity during evoked responses is inferred from recent physiology-based modeling of evoked response potentials (ERPs). A hemodynamic model is then used to calculate the BOLD response to neuronal activity. The predicted response is analyzed vs. form, frequency, and amplitude of stimulus. The BOLD frequency response is very nearly linear in the parameter ranges of interest, with the form of a low-pass filter with a weak resonance at 0.07 Hz. For short stimuli, the response is closely proportional to the time-integrated stimulus-evoked activity, rather than the peak amplitude, as often assumed. There can thus be widely differing proportionalities between BOLD and peak activity, a likely reason for the weak expected correlation between ERPs and BOLD.
Pain Does Not Follow the Boxcar Model: Temporal Dynamics of the BOLD FMRI Signal during Constant Current Painful Electric Nerve Stimulation
Ibinson, JW; Vogt, KM
The temporal dynamics of the blood oxygen level dependent (BOLD) signal, especially for painful stimulations, is not completely understood. In this study, the BOLD signal response to a long painful electrical stimulation (a continuous painful stimulation of 2 minutes) is directly compared to that of a short painful stimulation (four 30-s periods of painful stimulation interleaved with 30-s rest) in an effort to further probe the relationship between the temporal dynamics of the BOLD signal during constant intensity pain stimulation. Time course analysis showed that both stimulation protocols produced three similarly timed peaks in both data sets, suggesting an early and delayed BOLD response to painful stimulation initiation, and a response related to stimulus termination. Despite the continuous stimulation, the BOLD signal returned to baseline in the two-minute task. Even with this signal discrepancy, however, the activation maps of the two pain tasks differed only slightly, suggesting that the bulk of the activation is determined by the sharp rise in BOLD signal with stimulus onset. These findings imply that the BOLD signal response time course is not directly reflective of pain perception. PMID:24135433
The valuation system: A coordinate-based meta-analysis of BOLD fMRI experiments examining neural correlates of subjective value
Bartra, Oscar; McGuire, Joseph T.; Kable, Joseph W.
Numerous experiments have recently sought to identify neural signals associated with the subjective value (SV) of choice alternatives. Theoretically, SV assessment is an intermediate computational step during decision making, in which alternatives are placed on a common scale to facilitate value-maximizing choice. Here we present a quantitative, coordinate-based meta-analysis of 206 published fMRI studies investigating neural correlates of SV. Our results identify two general patterns of SV-correlated brain responses. In one set of regions, both positive and negative effects of SV on BOLD are reported at above-chance rates across the literature. Areas exhibiting this pattern include anterior insula, dorsomedial prefrontal cortex, dorsal and posterior striatum, and thalamus. The mixture of positive and negative effects potentially reflects an underlying U-shaped function, indicative of signal related to arousal or salience. In a second set of areas, including ventromedial prefrontal cortex and anterior ventral striatum, positive effects predominate. Positive effects in the latter regions are seen both when a decision is confronted and when an outcome is delivered, as well as for both monetary and primary rewards. These regions appear to constitute a "valuation system," carrying a domain-general SV signal and potentially contributing to value-based decision making. PMID:23507394
Variability of the BOLD response over time: an examination of within-session differences.
Menz, Mareike M; Neumann, Jane; Müller, Karsten; Zysset, Stefan
Model-based analysis methods for fMRI data assume a priori knowledge of the time course of the hemodynamic response (HR) in reaction to experimental stimuli or events. This knowledge is incorporated into the hemodynamic response function (HRF), which is a common model of the HR. Although it is already known that the HR varies across individuals and brain regions, few studies have investigated how variations within one session affect the results of statistical analysis using the general linear model (GLM). In this study, we formally tested for a possible variation of the BOLD response during prolonged functional measurement (120 min). To provoke performance of simple visual, motor, and cognitive tasks, we opted for a combination of a variant of the Stroop task and rotating L's. In selected regions of interest, time courses were extracted and compared with regard to mean and maximum amplitudes throughout the time of functional measurement. Additionally, parameter estimates derived from the GLM were tested for differences over time. Although differences between conditions were found to be significant, results did not show significant variance due to a within-factor time. Similarly, a temporal change in the relation between conditions, in terms of an interaction between the within-factor time and the within-factor condition, was not detectable by a repeated measures ANOVA. Similar results were obtained for analysis of mean and maximum amplitudes as well as for the analyses of parameter estimates.
Internal representations for face detection: an application of noise-based image classification to BOLD responses.
Nestor, Adrian; Vettel, Jean M; Tarr, Michael J
What basic visual structures underlie human face detection and how can we extract such structures directly from the amplitude of neural responses elicited by face processing? Here, we address these issues by investigating an extension of noise-based image classification to BOLD responses recorded in high-level visual areas. First, we assess the applicability of this classification method to such data and, second, we explore its results in connection with the neural processing of faces. To this end, we construct luminance templates from white noise fields based on the response of face-selective areas in the human ventral cortex. Using behaviorally and neurally-derived classification images, our results reveal a family of simple but robust image structures subserving face representation and detection. Thus, we confirm the role played by classical face selective regions in face detection and we help clarify the representational basis of this perceptual function. From a theory standpoint, our findings support the idea of simple but highly diagnostic neurally-coded features for face detection. At the same time, from a methodological perspective, our work demonstrates the ability of noise-based image classification in conjunction with fMRI to help uncover the structure of high-level perceptual representations.
Correlation between BOLD-fMRI and EEG signal changes in response to visual stimulus frequency in humans.
Singh, Manbir; Kim, Sungheon; Kim, Tae-Seong
The correlation between signals acquired using electroencephalography (EEG) and fMRI was investigated in humans during visual stimulation. Evoked potential EEG and BOLD fMRI data were acquired independently under similar conditions from eight subjects during stimulation by a checkerboard flashed at frequencies ranging from 2-12 Hz. The results indicate highly correlated changes in the strength of the EEG signal averaged over two occipital electrodes and the BOLD signal within the occipital lobe as a function of flash frequency for 7/8 subjects (average linear correlation coefficient of 0.76). Both signals peaked at approximately 8 Hz. For one subject the correlation coefficient was 0.20; the EEG signal peaked at 6 Hz and the BOLD signal peaked at 10 Hz. Overall, the EEG and BOLD signals, each averaged over 40-sec stimulation periods, appear to be coupled linearly during visual stimulation by a flashing checkerboard.
Negative BOLD response in the hippocampus during short-term spatial memory retrieval.
Nilsson, Jonna; Ferrier, I Nicol; Coventry, Kenny; Bester, Andre; Finkelmeyer, Andreas
A parieto-medial temporal pathway is thought to underlie spatial navigation in humans. fMRI was used to assess the role of this pathway, including the hippocampus, in the cognitive processes likely to underlie navigation based on environmental cues. Participants completed a short-term spatial memory task in virtual space, which required no navigation but involved the recognition of a target location from a foil location based on environmental landmarks. The results showed that spatial memory retrieval based on environmental landmarks was indeed associated with increased signal in regions of the parieto-medial temporal pathway, including the superior parietal cortex, the retrosplenial cortex, and the lingual gyrus. However, the hippocampus demonstrated a signal decrease below the fixation baseline during landmark-based retrieval, whereas there was no signal change from baseline during retrieval based on viewer position. In a discussion of the origins of such negative BOLD response in the hippocampus, we consider both a suppression of default activity and an increase in activity without a corresponding boost in CBF as possible mechanisms.
FMRI evidence of 'mirror' responses to geometric shapes.
Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey
Mirror neurons may be a genetic adaptation for social interaction. Alternatively, the associative hypothesis proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control.
Specificity of stimulus-evoked fMRI responses in the mouse: the influence of systemic physiological changes associated with innocuous stimulation under four different anesthetics.
Schroeter, Aileen; Schlegel, Felix; Seuwen, Aline; Grandjean, Joanes; Rudin, Markus
Functional magnetic resonance (fMRI) in mice has become an attractive tool for mechanistic studies, for characterizing models of human disease, and for evaluation of novel therapies. Yet, controlling the physiological state of mice is challenging, but nevertheless important as changes in cardiovascular parameters might affect the hemodynamic readout which constitutes the basics of the fMRI signal. In contrast to rats, fMRI studies in mice report less robust brain activation of rather widespread character to innocuous sensory stimulation. Anesthesia is known to influence the characteristics of the fMRI signal. To evaluate modulatory effects imposed by the anesthesia on stimulus-evoked fMRI responses, we compared blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) signal changes to electrical hindpaw stimulation using the four commonly used anesthetics isoflurane, medetomidine, propofol and urethane. fMRI measurements were complemented by assessing systemic physiological parameters throughout the experiment. Unilateral stimulation of the hindpaw elicited widespread fMRI responses in the mouse brain displaying a bilateral pattern irrespective of the anesthetic used. Analysis of magnitude and temporal profile of BOLD and CBV signals indicated anesthesia-specific modulation of cerebral hemodynamic responses and differences observed for the four anesthetics could be largely explained by their known effects on animal physiology. Strikingly, independent of the anesthetic used our results reveal that fMRI responses are influenced by stimulus-induced cardiovascular changes, which indicate an arousal response, even to innocuous stimulation. This may mask specific fMRI signal associated to the stimulus. Hence, studying the processing of peripheral input in mice using fMRI techniques constitutes a major challenge and adapted paradigms and/or alternative fMRI readouts should also be considered when studying sensory processing in mice.
Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression
Zotev, Vadim; Yuan, Han; Misaki, Masaya; Phillips, Raquel; Young, Kymberly D.; Feldner, Matthew T.; Bodurka, Jerzy
Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala
Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression.
Zotev, Vadim; Yuan, Han; Misaki, Masaya; Phillips, Raquel; Young, Kymberly D; Feldner, Matthew T; Bodurka, Jerzy
Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala
Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.
Wirsich, Jonathan; Bénar, Christian; Ranjeva, Jean-Philippe; Descoins, Médéric; Soulier, Elisabeth; Le Troter, Arnaud; Confort-Gouny, Sylviane; Liégeois-Chauvel, Catherine; Guye, Maxime
Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe.
Delineating the whole brain BOLD response to passive movement kinematics.
Sulzer, James; Dueñas, Julio; Stämpili, Philipp; Hepp-Reymond, Marie-Claude; Kollias, Spyros; Seifritz, Erich; Gassert, Roger
The field of brain-machine interfaces (BMIs) has made great advances in recent years, converting thought to movement, with some of the most successful implementations measuring directly from the motor cortex. However, the ability to record from additional regions of the brain could potentially improve flexibility and robustness of use. In addition, BMIs of the future will benefit from integrating kinesthesia into the control loop. Here, we examine whether changes in passively induced forefinger movement amplitude are represented in different regions than forefinger velocity via a MR compatible robotic manipulandum. Using functional magnetic resonance imaging (fMRI), five healthy participants were exposed to combinations of forefinger movement amplitude and velocity in a factorial design followed by an epoch-based analysis. We found that primary and secondary somatosensory regions were activated, as well as cingulate motor area, putamen and cerebellum, with greater activity from changes in velocity compared to changes in amplitude. This represents the first investigation into whole brain response to parametric changes in passive movement kinematics. In addition to informing BMIs, these results have implications towards neural correlates of robotic rehabilitation.
BOLD Frequency Power Indexes Working Memory Performance.
Balsters, Joshua Henk; Robertson, Ian H; Calhoun, Vince D
Electrophysiology studies routinely investigate the relationship between neural oscillations and task performance. However, the sluggish nature of the BOLD response means that few researchers have investigated the spectral properties of the BOLD signal in a similar manner. For the first time we have applied group ICA to fMRI data collected during a standard working memory task (delayed match-to-sample) and using a multivariate analysis, we investigate the relationship between working memory performance (accuracy and reaction time) and BOLD spectral power within functional networks. Our results indicate that BOLD spectral power within specific networks (visual, temporal-parietal, posterior default-mode network, salience network, basal ganglia) correlated with task accuracy. Multivariate analyses show that the relationship between task accuracy and BOLD spectral power is stronger than the relationship between BOLD spectral power and other variables (age, gender, head movement, and neuropsychological measures). A traditional General Linear Model (GLM) analysis found no significant group differences, or regions that covaried in signal intensity with task accuracy, suggesting that BOLD spectral power holds unique information that is lost in a standard GLM approach. We suggest that the combination of ICA and BOLD spectral power is a useful novel index of cognitive performance that may be more sensitive to brain-behavior relationships than traditional approaches.
Neural and vascular variability and the fMRI-BOLD response in normal aging.
Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B
Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19-27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55-71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response.
Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults
Hantke, Nathan; Nielson, Kristy A.; Woodard, John L.; Guidotti Breting, Leslie M.; Butts, Alissa; Seidenberg, Michael; Smith, J. Carson; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A.; Rao, Stephen M.
Previous studies suggest that task-activated fMRI can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with APOE ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease. PMID:23199565
Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers
Versace, Francesco; Engelmann, Jeffrey M.; Jackson, Edward F.; Costa, Vincent D.; Robinson, Jason D.; Lam, Cho Y.; Minnix, Jennifer A.; Brown, Victoria L.; Cinciripini, Paul M.
Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing 1) would be more active during exposure to cigarette-related than neutral pictures, and 2) would be less active to pleasant compared to cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole brain blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli. PMID:22097928
Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients
Garza-Villarreal, Eduardo A.; Jiang, Zhiguo; Vuust, Peter; Alcauter, Sarael; Vase, Lene; Pasaye, Erick H.; Cavazos-Rodriguez, Roberto; Brattico, Elvira; Jensen, Troels S.; Barrios, Fernando A.
Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN). PMID:26257695
NMDA-dependent mechanisms only affect the BOLD response in the rat dentate gyrus by modifying local signal processing
Tiede, Regina; Krautwald, Karla; Fincke, Anja; Angenstein, Frank
The role of N-methyl--aspartate (NMDA) receptor-mediated mechanisms in the formation of a blood oxygen level-dependent (BOLD) response was studied using electrical stimulation of the right perforant pathway. Stimulation of this fiber bundle triggered BOLD responses in the right hippocampal formation and in the left entorhinal cortex. The perforant pathway projects to and activates the dentate gyrus monosynaptically, activation in the contralateral entorhinal cortex is multisynaptic and requires forwarding and processing of signals. Application of the NMDA receptor antagonist MK801 during stimulation had no effect on BOLD responses in the right dentate gyrus, but reduced the BOLD responses in the left entorhinal cortex. In contrast, application of MK801 before the first stimulation train reduced the BOLD response in both regions. Electrophysiological recordings revealed that the initial stimulation trains changed the local processing of the incoming signals in the dentate gyrus. This altered electrophysiological response was not further changed by a subsequent application of MK801, which is in agreement with an unchanged BOLD response. When MK801 was present during the first stimulation train, a dissimilar electrophysiological response pattern was observed and corresponds to an altered BOLD response, indicating that NMDA-dependent mechanisms indirectly affect the BOLD response, mainly via modifying local signal processing and subsequent propagation. PMID:22167232
The hemodynamic response to somatosensory stimulation in mice depends on the anesthetic used: Implications on analysis of mouse fMRI data.
Schlegel, Felix; Schroeter, Aileen; Rudin, Markus
In recent years, the number of functional MRI (fMRI) studies in mice has been rapidly increasing. Technological improvements provide the sensitivity required to match the high demands on spatial and temporal resolution and to analyze fast and small signal components of the fMRI response. Yet, the interpretation of mouse fMRI data largely relies on assumptions that were uncritically adopted from previous research in humans or rats. Here, we show based on a large dataset employing an innocuous electrical stimulation paradigm, that (1) the shape of the HRF shapes comprises significant transient signal components; correspondingly analysis procedures have to account for this dynamic nature and allow for variable response functions. (2) The effects of the anesthetics are crucial in determining the shape of the hemodynamic response function (HRF) and also influence the spatial specificity of BOLD signal. (3) The dominant systemic confounding contributions elicited by stimulus-evoked cardiovascular responses observed in mouse fMRI when applying block stimuli may be largely avoided by a milder event-related design applying a randomly spaced single pulse train (RSSPT). Thereby the spatial specificity of the fMRI response is largely retained. We conclude that the sensitivity, specificity and interpretability of stimulus-evoked BOLD signals in mice can be improved by combining appropriate stimulation paradigms with analysis procedures that include adapted HRFs.
Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level.
Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis
The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation- a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system's responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2.
Test-retest reliability of evoked BOLD signals from a cognitive-emotive fMRI test battery.
Plichta, Michael M; Schwarz, Adam J; Grimm, Oliver; Morgen, Katrin; Mier, Daniela; Haddad, Leila; Gerdes, Antje B M; Sauer, Carina; Tost, Heike; Esslinger, Christine; Colman, Peter; Wilson, Frederick; Kirsch, Peter; Meyer-Lindenberg, Andreas
Even more than in cognitive research applications, moving fMRI to the clinic and the drug development process requires the generation of stable and reliable signal changes. The performance characteristics of the fMRI paradigm constrain experimental power and may require different study designs (e.g., crossover vs. parallel groups), yet fMRI reliability characteristics can be strongly dependent on the nature of the fMRI task. The present study investigated both within-subject and group-level reliability of a combined three-task fMRI battery targeting three systems of wide applicability in clinical and cognitive neuroscience: an emotional (face matching), a motivational (monetary reward anticipation) and a cognitive (n-back working memory) task. A group of 25 young, healthy volunteers were scanned twice on a 3T MRI scanner with a mean test-retest interval of 14.6 days. FMRI reliability was quantified using the intraclass correlation coefficient (ICC) applied at three different levels ranging from a global to a localized and fine spatial scale: (1) reliability of group-level activation maps over the whole brain and within targeted regions of interest (ROIs); (2) within-subject reliability of ROI-mean amplitudes and (3) within-subject reliability of individual voxels in the target ROIs. Results showed robust evoked activation of all three tasks in their respective target regions (emotional task=amygdala; motivational task=ventral striatum; cognitive task=right dorsolateral prefrontal cortex and parietal cortices) with high effect sizes (ES) of ROI-mean summary values (ES=1.11-1.44 for the faces task, 0.96-1.43 for the reward task, 0.83-2.58 for the n-back task). Reliability of group level activation was excellent for all three tasks with ICCs of 0.89-0.98 at the whole brain level and 0.66-0.97 within target ROIs. Within-subject reliability of ROI-mean amplitudes across sessions was fair to good for the reward task (ICCs=0.56-0.62) and, dependent on the particular ROI
Bold-Independent Computational Entropy Assesses Functional Donut-Like Structures in Brain fMRI Images
Peters, James F.; Ramanna, Sheela; Tozzi, Arturo; İnan, Ebubekir
We introduce a novel method for the measurement of information level in fMRI (functional Magnetic Resonance Imaging) neural data sets, based on image subdivision in small polygons equipped with different entropic content. We show how this method, called maximal nucleus clustering (MNC), is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals. MNC facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. This approach befits the geometric character of fMRIs. The main purpose of this study is to provide a computable framework for fMRI that not only facilitates analyses, but also provides an easily decipherable visualization of structures. This framework commands attention because it is easily implemented using conventional software systems. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension's distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain. PMID:28203153
Bold-Independent Computational Entropy Assesses Functional Donut-Like Structures in Brain fMRI Images.
Peters, James F; Ramanna, Sheela; Tozzi, Arturo; İnan, Ebubekir
We introduce a novel method for the measurement of information level in fMRI (functional Magnetic Resonance Imaging) neural data sets, based on image subdivision in small polygons equipped with different entropic content. We show how this method, called maximal nucleus clustering (MNC), is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals. MNC facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. This approach befits the geometric character of fMRIs. The main purpose of this study is to provide a computable framework for fMRI that not only facilitates analyses, but also provides an easily decipherable visualization of structures. This framework commands attention because it is easily implemented using conventional software systems. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension's distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain.
Neural signatures of experimentally induced flow experiences identified in a typical fMRI block design with BOLD imaging
Keller, Johannes; Grön, Georg
Previously, experimentally induced flow experiences have been demonstrated with perfusion imaging during activation blocks of 3 min length to accommodate with the putatively slowly evolving "mood" characteristics of flow. Here, we used functional magnetic resonance imaging (fMRI) in a sample of 23 healthy, male participants to investigate flow in the context of a typical fMRI block design with block lengths as short as 30 s. To induce flow, demands of arithmetic tasks were automatically and continuously adjusted to the individual skill level. Compared against conditions of boredom and overload, experience of flow was evident from individuals' reported subjective experiences and changes in electrodermal activity. Neural activation was relatively increased during flow, particularly in the anterior insula, inferior frontal gyri, basal ganglia and midbrain. Relative activation decreases during flow were observed in medial prefrontal and posterior cingulate cortex, and in the medial temporal lobe including the amygdala. Present findings suggest that even in the context of comparably short activation blocks flow can be reliably experienced and is associated with changes in neural activation of brain regions previously described. Possible mechanisms of interacting brain regions are outlined, awaiting further investigation which should now be possible given the greater temporal resolution compared with previous perfusion imaging. PMID:26508774
Variability of the coupling of blood flow and oxygen metabolism responses in the brain: a problem for interpreting BOLD studies but potentially a new window on the underlying neural activity
Buxton, Richard B.; Griffeth, Valerie E. M.; Simon, Aaron B.; Moradi, Farshad
Recent studies from our group and others using quantitative fMRI methods have found that variations of the coupling ratio of blood flow (CBF) and oxygen metabolism (CMRO2) responses to a stimulus have a strong effect on the BOLD response. Across a number of studies an empirical pattern is emerging in the way CBF and CMRO2 changes are coupled to neural activation: if the stimulus is modulated to create a stronger response (e.g., increasing stimulus contrast), CBF is modulated more than CMRO2; on the other hand, if the brain state is altered such that the response to the same stimulus is increased (e.g., modulating attention, adaptation, or excitability), CMRO2 is modulated more than CBF. Because CBF and CMRO2 changes conflict in producing BOLD signal changes, this finding has an important implication for conventional BOLD-fMRI studies: the BOLD response exaggerates the effects of stimulus variation but is only weakly sensitive to modulations of the brain state that alter the response to a standard stimulus. A speculative hypothesis is that variability of the coupling ratio of the CBF and CMRO2 responses reflects different proportions of inhibitory and excitatory evoked activity, potentially providing a new window on neural activity in the human brain. PMID:24966808
Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study.
Nahas, Ziad; George, Mark S; Horner, Michael D; Markowitz, John S; Li, Xingbao; Lorberbaum, Jeffrey P; Owens, Susan D; McGurk, Susan; DeVane, Lindsay; Risch, S Craig
Cognitive impairments are cardinal features of schizophrenia and predictors of poor vocational and social outcome. Imaging studies with verbal fluency tasks (VFT) lead some to suggest that in schizophrenia, the combination of a failure to deactivate the left temporal lobe and a hypoactive frontal lobe reflects a functional disconnectivity between the left prefrontal cortex and temporal lobe. Others have theorized that an abnormal cingulate gyrus modulates such fronto-temporal connectivity. Thus addition of a cognitive enhancing medication to current antipsychotic therapy might improve functionality of networks necessary in working memory and internal concept generation. To test this hypothesis, we serially measured brain activity in 6 subjects on stable atypical antipsychotics performing a VFT, using BOLD fMRI. Measurements were made at baseline and again after groups were randomized to receive 12 weeks of donepezil (an acetylcholinesterase inhibitor) and placebo in a blind cross-over design. Donepezil addition provided a functional normalization with an increase in left frontal lobe and cingulate activity when compared to placebo and from baseline scans. This pilot study supports the cingulate's role in modulating cognition and neuronal connectivity in schizophrenia.
Application of fMRI to obesity research: differences in reward pathway activation measured with fMRI BOLD during visual presentation of high and low calorie foods
NASA Astrophysics Data System (ADS)
Tsao, Sinchai; Adam, Tanja C.; Goran, Michael I.; Singh, Manbir
The factors behind the neural mechanisms that motivate food choice and obesity are not well known. Furthermore, it is not known when these neural mechanisms develop and how they are influenced by both genetic and environmental factors. This study uses fMRI together with clinical data to shed light on the aforementioned questions by investigating how appetite-related activation in the brain changes with low versus high caloric foods in pre-pubescent girls. Previous studies have shown that obese adults have less striatal D2 receptors and thus reduced Dopamine (DA) signaling leading to the reward-deficit theory of obesity. However, overeating in itself reduces D2 receptor density, D2 sensitivity and thus reward sensitivity. The results of this study will show how early these neural mechanisms develop and what effect the drastic endocrinological changes during puberty has on these mechanisms. Our preliminary results showed increased activations in the Putamen, Insula, Thalamus and Hippocampus when looking at activations where High Calorie > Low Calorie. When comparing High Calorie > Control and Low Calorie > Control, the High > Control test showed increased significant activation in the frontal lobe. The Low > Control also yielded significant activation in the Left and Right Fusiform Gyrus, which did not appear in the High > Control test. These results indicate that the reward pathway activations previously shown in post-puberty and adults are present in pre-pubescent teens. These results may suggest that some of the preferential neural mechanisms of reward are already present pre-puberty.
Joint maximum likelihood estimation of activation and Hemodynamic Response Function for fMRI.
Bazargani, Negar; Nosratinia, Aria
Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) maps the brain activity by measuring blood oxygenation level, which is related to brain activity via a temporal impulse response function known as the Hemodynamic Response Function (HRF). The HRF varies from subject to subject and within areas of the brain, therefore a knowledge of HRF is necessary for accurately computing voxel activations. Conversely a knowledge of active voxels is highly beneficial for estimating the HRF. This work presents a joint maximum likelihood estimation of HRF and activation based on low-rank matrix approximations operating on regions of interest (ROI). Since each ROI has limited data, a smoothing constraint on the HRF is employed via Tikhonov regularization. The method is analyzed under both white noise and colored noise. Experiments with synthetic data show that accurate estimation of the HRF is possible with this method without prior assumptions on the exact shape of the HRF. Further experiments involving real fMRI experiments with auditory stimuli are used to validate the proposed method.
Citicoline Treatment Improves Measures of Impulsivity and Task Performance in Chronic Marijuana Smokers: A Pilot BOLD fMRI Study
Gruber, Staci A.; Sagar, Kelly A.; Dahlgren, Mary Kathryn; Gonenç, Atilla; Conn, Nina A.; Winer, Jeffrey P.; Penetar, David; Lukas, Scott E.
Objective Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo. Method The current study tested this hypothesis by examining the effects of citicoline in treatment-seeking chronic MJ smokers. In an 8-week double-blind, placebo-controlled study, 19 MJ smokers were randomly assigned via a double-blind procedure to the citicoline (8 Males, 2 Females) or placebo group (9 Males, 0 Females). All participants completed fMRI scanning at baseline and after 8 weeks of treatment during two cognitive measures of inhibitory processing, the Multi Source Interference Test (MSIT) and Stroop Color Word Test, and also completed the Barratt Impulsiveness Scale (BIS-11), a self-report measure of impulsivity. Results Following the 8 week trial, MJ smokers treated with citicoline demonstrated significantly lower levels of behavioral impulsivity, improved task accuracy on both the MSIT and Stroop tasks, and exhibited significantly different patterns of brain activation relative to baseline levels and relative to those who received placebo. Conclusions Findings suggest that citicoline may facilitate the treatment of MJ use disorders by improving the cognitive skills necessary to fully engage in comprehensive treatment programs. PMID:26658924
One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament
Cook, Peter F.; Spivak, Mark
Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog's respective handler), an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog's general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer). A group-level psychophysiological interaction (PPI) connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications pertinent to the training
Comparing consistency of R2* and T2*-weighted BOLD analysis of resting state fetal fMRI
NASA Astrophysics Data System (ADS)
Seshamani, Sharmishtaa; Blazejewska, Anna I.; Gatenby, Christopher; Mckown, Susan; Caucutt, Jason; Dighe, Manjiri; Studholme, Colin
Understanding when and how resting state brain functional activity begins in the human brain is an increasing area of interest in both basic neuroscience and in the clinical evaluation of the brain during pregnancy and after premature birth. Although fMRI studies have been carried out on pregnant women since the 1990's, reliable mapping of brain function in utero is an extremely challenging problem due to the unconstrained fetal head motion. Recent studies have employed scrubbing to exclude parts of the time series and whole subjects from studies in order to control the confounds of motion. Fundamentally, even after correction of the location of signals due to motion, signal intensity variations are a fundamental limitation, due to coil sensitivity and spin history effects. An alternative technique is to use a more parametric MRI signal derived from multiple echoes that provides a level of independence from basic MRI signal variation. Here we examine the use of R2* mapping combined with slice based multi echo geometric distortion correction for in-utero studies. The challenges for R2* mapping arise from the relatively low signal strength of in-utero data. In this paper we focus on comparing activation detection in-utero using T2W and R2* approaches. We make use a subset of studies with relatively limited motion to compare the activation patterns without the additional confound of significant motion. Results at different gestational ages indicate comparable agreement in many activation patterns when limited motion is present, and the detection of some additional networks in the R2* data, not seen in the T2W results.
Prolactin and fMRI response to SKF38393 in the baboon
Miller, Brad; Marks, Lauren A.; Koller, Jonathan M.; Newman, Blake J.; Bretthorst, G. Larry
Background. This study's goal was to provide dose–response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps ("time course studies") were performed with three agonists, and the results were used to select promising agonists and to guide design details for the single-dose studies needed to generate dose–response curves. Methods. We studied 6 male baboons (Papio anubis) under low-dose isoflurane anesthesia after i.m. ketamine. Time course studies charted the changes in plasma prolactin levels over time after anesthesia alone or after an intravenous (i.v.) dose of the dopamine D1-like agonists SKF82958 and SKF38393 or the D2-like agonist pramipexole. In the single-dose dopamine agonist studies, one dose of SKF38393 (ranging from 0.0928–9.28 mg/kg, N = 5 animals) or pramipexole (0.00928–0.2 mg/kg, N = 1) was given i.v. during a 40-min blood oxygen level dependent (BOLD) fMRI session, to determine BOLD and plasma prolactin responses to different drug concentrations. BOLD response was quantified as the area under the time-signal curve for the first 15 min after the start of the drug infusion, compared to the linearly predicted signal from the baseline data before drug. The ED50 (estimated dose that produces 50% of the maximal possible response to drug) for SKF38393 was calculated for the serum prolactin response and for phMRI responses in hypothalamus, pituitary, striatum and midbrain. Results. Prolactin rose 2.4- to 12-fold with anesthesia alone, peaking around 50–90 min after ketamine administration
Cerebellar lobules and dentate nuclei mirror cortical force-related-BOLD responses: Beyond all (linear) expectations.
Alahmadi, Adnan A S; Pardini, Matteo; Samson, Rebecca S; Friston, Karl J; Toosy, Ahmed T; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M
The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum-optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non-linear associations between cerebellar activations and forces. We showed extensive non-linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD-force relationship that is region-dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Comparison of Muscle BOLD Responses to Arterial Occlusion at 3T and 7T
Towse, Theodore F.; Childs, Benjamin T.; Sabin, Shea A.; Bush, Emily C.; Elder, Christopher P.; Damon, Bruce M.
Purpose The purpose of this study was to determine the feasibility of muscle BOLD (mBOLD) imaging at 7T by comparing the changes in R2* of muscle at 3 and 7T in response to a brief period of tourniquet-induced ischemia. Methods Eight subjects (3 male), aged 29.5 ± 6.1 years (mean ± standard deviation, SD), 167.0 ± 10.6 cm tall with a body mass of 62.0 ± 18.0 kg, participated in the study. Subjects reported to the lab on four separate occasions including a habituation session, two MRI scans, and in a subset of subjects, a session during which changes in blood flow and blood oxygenation were quantified using Doppler ultrasound (U/S) and near-infrared spectroscopy (NIRS) respectively. For statistical comparisons between 3T and 7T, R2* rate constants were calculated as R2* = 1/T2*. Results The mean pre-occlusion R2* value was greater at 7T than at 3T (60.16 ± 2.95 vs 35.17 ± 0.35 s−1 respectively, p <0.001). Also, the mean ΔR2*END and ΔR2*POST values were greater for 7T than for 3T (−2.36 ± 0.25 vs. −1.24 ± 0.39 s−1, respectively, Table 1). Conclusion Muscle BOLD contrast at 7T is as much as six-fold greater than at 3T. In addition to providing greater SNR and CNR, 7T mBOLD studies may offer further advantages in the form of greater sensitivity to pathological changes in the muscle microcirculation. PMID:25884888
Negative cerebral blood volume fMRI response coupled with Ca²⁺-dependent brain activity in a dopaminergic road map of nociception.
Hsu, Yi-Hua; Chang, Chen; Chen, Chiao-Chi V
Decreased cerebral blood volume/flow (CBV/CBF) contributes to negative blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signals. But it is still strongly debated whether these negative BOLD or CBV/CBF signals are indicative of decreased or increased neuronal activity. The fidelity of Ca(2+) signals in reflecting neuronal excitation is well documented. However, the roles of Ca(2+) signals and Ca(2+)-dependent activity in negative fMRI signals have never been explored; an understanding of this is essential to unraveling the underlying mechanisms and correctly interpreting the hemodynamic response of interest. The present study utilized a nociception-induced negative CBV fMRI response as a model. Ca(2+) signals were investigated in vivo using Mn(2+)-enhanced MRI (MEMRI), and the downstream Ca(2+)-dependent signaling was investigated using phosphorylated cAMP response-element-binding (pCREB) immunohistology. The results showed that nociceptive stimulation led to (1) striatal CBV decreases, (2) Ca(2+) increases via the nigrostriatal pathway, and (3) substantial expression of pCREB in substantia nigra dopaminergic neurons and striatal neurons. Interestingly, the striatal negative fMRI response was abolished by blocking substantia nigra activity but was not affected by blocking the striatal activity. This suggests the importance of input activity other than output in triggering the negative CBV signals. These findings indicate that the striatal negative CBV fMRI signals are associated with Ca(2+) increases and Ca(2+)-dependent signaling along the nigrostriatal pathway. The obtained data reveal a new brain road map in response to nociceptive stimulation of hemodynamic changes in association with Ca(2+) signals within the dopaminergic system.
Replicability and heterogeneity of awake unrestrained canine FMRI responses.
Berns, Gregory S; Brooks, Andrew; Spivak, Mark
Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs.
Gestational Valproate Alters BOLD Activation in Response to Complex Social and Primary Sensory Stimuli
Felix-Ortiz, Ada C.; Febo, Marcelo
Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light) to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V1a neurotransmission. PMID:22615973
A two-stage cascade model of BOLD responses in human visual cortex.
Kay, Kendrick N; Winawer, Jonathan; Rokem, Ariel; Mezer, Aviv; Wandell, Brian A
Visual neuroscientists have discovered fundamental properties of neural representation through careful analysis of responses to controlled stimuli. Typically, different properties are studied and modeled separately. To integrate our knowledge, it is necessary to build general models that begin with an input image and predict responses to a wide range of stimuli. In this study, we develop a model that accepts an arbitrary band-pass grayscale image as input and predicts blood oxygenation level dependent (BOLD) responses in early visual cortex as output. The model has a cascade architecture, consisting of two stages of linear and nonlinear operations. The first stage involves well-established computations-local oriented filters and divisive normalization-whereas the second stage involves novel computations-compressive spatial summation (a form of normalization) and a variance-like nonlinearity that generates selectivity for second-order contrast. The parameters of the model, which are estimated from BOLD data, vary systematically across visual field maps: compared to primary visual cortex, extrastriate maps generally have larger receptive field size, stronger levels of normalization, and increased selectivity for second-order contrast. Our results provide insight into how stimuli are encoded and transformed in successive stages of visual processing.
Separating neural and vascular effects of caffeine using simultaneous EEG-FMRI: differential effects of caffeine on cognitive and sensorimotor brain responses.
Diukova, Ana; Ware, Jennifer; Smith, Jessica E; Evans, C John; Murphy, Kevin; Rogers, Peter J; Wise, Richard G
The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19
Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura.
Hougaard, Anders; Amin, Faisal Mohammad; Hoffmann, Michael B; Rostrup, Egill; Larsson, Henrik B W; Asghar, Mohammad Sohail; Larsen, Vibeke Andrée; Olesen, Jes; Ashina, Messoud
Migraine sufferers with aura often report photosensitivity and visual discomfort outside of attacks and many consider bright or flickering light an attack-precipitating factor. The nature of this visual hypersensitivity and its relation to the underlying pathophysiology of the migraine aura is unknown. Using fMRI measurements during visual stimulation we examined the visual cortical responsiveness of patients with migraine with aura. We applied a within-patient design by assessing functional interhemispheric differences in patients consistently experiencing visual aura in the same visual hemifield. We recruited 20 patients with frequent side-fixed visual aura attacks (≥90% of auras occurring in the same visual hemifield) and 20 age and sex matched healthy controls and compared the fMRI blood oxygenation level dependent (BOLD) responses to visual stimulation between symptomatic and asymptomatic hemispheres during the interictal phase and between migraine patients and controls. BOLD responses were selectively increased in the symptomatic hemispheres. This was found in the inferior parietal lobule (P = 0.002), the inferior frontal gyrus (P = 0.003), and the superior parietal lobule (P = 0.017). The affected cortical areas comprise a visually driven functional network involved in oculomotor control, guidance of movement, motion perception, visual attention, and visual spatial memory. The patients also had significantly increased response in the same cortical areas when compared to controls (P < 0.05). We discovered a lateralized alteration of a visually driven functional network in patients with side-fixed aura. These findings suggest a hyperexcitability of the visual system in the interictal phase of migraine with visual aura.
Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.
Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne
Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.
Failure to modulate neural response to increased task demand in mild Alzheimer's disease: fMRI study of visuospatial processing.
Vannini, Patrizia; Lehmann, Christoph; Dierks, Thomas; Jann, Kay; Viitanen, Matti; Wahlund, Lars-Olof; Almkvist, Ove
Alzheimer's disease (AD) is characterized by disturbances of visuospatial cognition. Given that these impairments are closely related to metabolic and neuropathological changes, our study aimed to investigate the functional competency of brain regions in the visuospatial networks responsible for early clinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Participants (13AD patients with mild symptoms and 13 age- and education-matched controls) performed an angle discrimination task with varying task demand. Using a novel approach that modeled the dependency of the blood oxygenation level-dependent (BOLD) signal on the subject's reaction time allowed us to investigate task demand-dependent signal changes between the groups. Both groups demonstrated overlapping neural networks engaged in angle discrimination, including the parieto-occipital and frontal regions. In several network regions, AD patients showed a significantly weaker and sometimes no BOLD signal due to increased task demand compared with controls, demonstrating failure to modulate the neural response to increased task demand. A general task demand-independent increase of activation in AD patients compared with controls was found in right middle temporal gyrus. This latter finding may indicate an attempt to compensate for dysfunctional areas in the dorsal visual pathway. These results confirm deficits in visuospatial abilities, which occur early in AD, and offer new insights into the neural mechanisms underlying this impairment.
Pharmacological fMRI--challenges in analysing drug-induced single-event BOLD responses.
Pohlmann, Andreas; Barjat, Hervé; Tilling, Lorna C; James, Michael F
The interest in BOLD contrast based phMRI is likely to increase in the coming years, but detecting a direct modulation of regional brain activity by drugs presents a challenging problem. Based on in-vivo MRI and simulations we highlight some of the issues in detecting especially small BOLD signals in rat phMRI experiments.
Variability of the Relationship between Electrophysiology and BOLD-fMRI across Cortical Regions in Humans
Conner, Christopher R.; Ellmore, Timothy M.; Pieters, Thomas A.; DiSano, Michael A.; Tandon, Nitin
The relationship between blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal and the underlying neural electrical activity in humans is a topic of intense interest to systems neuroscience. This relationship has generally been assumed to be invariant regardless of the brain region and the cognitive task being studied. We critically evaluated these assumptions by comparing the BOLD-fMRI response with local field potential (LFP) measurements during visually cued common noun and verb generation in 11 humans in whom 1210 subdural electrodes were implanted. As expected, power in the mid-gamma band (60 –120 Hz) correlated positively (r2 = 0.16, p < 10−16) and power in the beta band (13–30 Hz) correlated negatively (r2 = 0.09, p < 10−16) with the BOLD signal change. Beta and mid-gamma band activity independently explain different components of the observed BOLD signal. Importantly, we found that the location (i.e., lobe) of the recording site modulates the relationship between the electrocorticographic (ECoG) signal and the observed fMRI response (p < 10−16, F21,1830 = 52.7), while the type of language task does not. Across all brain regions, ECoG activity in the gamma and beta bands explains 22% of the fMRI response, but if the lobar location is considered, 28% of the variance can be explained. Further evaluation of this relationship at the level of individual gyri provides additional evidence of differences in the BOLD-LFP relationship by cortical locus. This spatial variability in the relationship between the fMRI signal and neural activity carries implications for modeling of the hemodynamic response function, an essential step for interregional fMRI comparisons. PMID:21900564
Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities
Marchant, Jennifer L; Ruff, Christian C; Driver, Jon
The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980
Using fMRI to Test Models of Complex Cognition
ERIC Educational Resources Information Center
Anderson, John R.; Carter, Cameron S.; Fincham, Jon M.; Qin, Yulin; Ravizza, Susan M.; Rosenberg-Lee, Miriam
This article investigates the potential of fMRI to test assumptions about different components in models of complex cognitive tasks. If the components of a model can be associated with specific brain regions, one can make predictions for the temporal course of the BOLD response in these regions. An event-locked procedure is described for dealing…
Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.
Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W
A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.
Quantitative comparisons on hand motor functional areas determined by resting state and task BOLD fMRI and anatomical MRI for pre-surgical planning of patients with brain tumors.
Hou, Bob L; Bhatia, Sanjay; Carpenter, Jeffrey S
For pre-surgical planning we present quantitative comparison of the location of the hand motor functional area determined by right hand finger tapping BOLD fMRI, resting state BOLD fMRI, and anatomically using high resolution T1 weighted images. Data were obtained on 10 healthy subjects and 25 patients with left sided brain tumors. Our results show that there are important differences in the locations (i.e., > 20 mm) of the determined hand motor voxels by these three MR imaging methods. This can have significant effect on the pre-surgical planning of these patients depending on the modality used. In 13 of the 25 cases (i.e., 52%) the distances between the task-determined and the rs-fMRI determined hand areas were more than 20 mm; in 13 of 25 cases (i.e., 52%) the distances between the task-determined and anatomically determined hand areas were > 20 mm; and in 16 of 25 cases (i.e., 64%) the distances between the rs-fMRI determined and anatomically determined hand areas were more than 20 mm. In just three cases, the distances determined by all three modalities were within 20 mm of each other. The differences in the location or fingerprint of the hand motor areas, as determined by these three MR methods result from the different underlying mechanisms of these three modalities and possibly the effects of tumors on these modalities.
Physiologically informed dynamic causal modeling of fMRI data.
Havlicek, Martin; Roebroeck, Alard; Friston, Karl; Gardumi, Anna; Ivanov, Dimo; Uludag, Kamil
The functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and the BOLD signal equation. These generative models have been employed both for single brain area deconvolution and to infer effective connectivity in networks of multiple brain areas. In the current paper, we introduce a new fMRI model inspired by experimental observations about the physiological underpinnings of the BOLD signal and compare it with the generative models currently used in dynamic causal modeling (DCM), a widely used framework to study effective connectivity in the brain. We consider three fundamental aspects of such generative models for fMRI: (i) an adaptive two-state neuronal model that accounts for a wide repertoire of neuronal responses during and after stimulation; (ii) feedforward neurovascular coupling that links neuronal activity to blood flow; and (iii) a balloon model that can account for vascular uncoupling between the blood flow and the blood volume. Finally, we adjust the parameterization of the BOLD signal equation for different magnetic field strengths. This paper focuses on the form, motivation and phenomenology of DCMs for fMRI and the characteristics of the various models are demonstrated using simulations. These simulations emphasize a more accurate modeling of the transient BOLD responses - such as adaptive decreases to sustained inputs during stimulation and the post-stimulus undershoot. In addition, we demonstrate using experimental data that it is necessary to take into account both neuronal and vascular transients to accurately model the signal dynamics of fMRI data. By refining the models of the transient responses, we provide a more informed perspective on the underlying neuronal
Effects of anesthesia on BOLD signal and neuronal activity in the somatosensory cortex
Aksenov, Daniil P; Li, Limin; Miller, Michael J; Iordanescu, Gheorghe; Wyrwicz, Alice M
Most functional magnetic resonance imaging (fMRI) animal studies rely on anesthesia, which can induce a variety of drug-dependent physiological changes, including depression of neuronal activity and cerebral metabolism as well as direct effects on the vasculature. The goal of this study was to characterize the effects of anesthesia on the BOLD signal and neuronal activity. Simultaneous fMRI and electrophysiology were used to measure changes in single units (SU), multi-unit activity (MUA), local field potentials (LFP), and the blood oxygenation level-dependent (BOLD) response in the somatosensory cortex during whisker stimulation of rabbits before, during and after anesthesia with fentanyl or isoflurane. Our results indicate that anesthesia modulates the BOLD signal as well as both baseline and stimulus-evoked neuronal activity, and, most significantly, that the relationship between the BOLD and electrophysiological signals depends on the type of anesthetic. Specifically, the behavior of LFP observed under isoflurane did not parallel the behavior of BOLD, SU, or MUA. These findings suggest that the relationship between these signals may not be straightforward. BOLD may scale more closely with the best measure of the excitatory subcomponents of the underlying neuronal activity, which may vary according to experimental conditions that alter the excitatory/inhibitory balance in the cortex. PMID:26104288
BOLD Response Selective to Flow-Motion in Very Young Infants
Tosetti, Michela; Morrone, Maria Concetta
In adults, motion perception is mediated by an extensive network of occipital, parietal, temporal, and insular cortical areas. Little is known about the neural substrate of visual motion in infants, although behavioural studies suggest that motion perception is rudimentary at birth and matures steadily over the first few years. Here, by measuring Blood Oxygenated Level Dependent (BOLD) responses to flow versus random-motion stimuli, we demonstrate that the major cortical areas serving motion processing in adults are operative by 7 wk of age. Resting-state correlations demonstrate adult-like functional connectivity between the motion-selective associative areas, but not between primary cortex and temporo-occipital and posterior-insular cortices. Taken together, the results suggest that the development of motion perception may be limited by slow maturation of the subcortical input and of the cortico-cortical connections. In addition they support the existence of independent input to primary (V1) and temporo-occipital (V5/MT+) cortices very early in life. PMID:26418729
Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization.
Fera, Francesco; Passamonti, Luca; Herzallah, Mohammad M; Myers, Catherine E; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A
To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands.
Nonlinear estimation of the BOLD signal.
Johnston, Leigh A; Duff, Eugene; Mareels, Iven; Egan, Gary F
Signal variations in functional Magnetic Resonance Imaging experiments essentially reflect the vascular system response to increased demand for oxygen caused by neuronal activity, termed the blood oxygenation level dependent (BOLD) effect. The most comprehensive model to date of the BOLD signal is formulated as a mixed continuous-discrete-time system of nonlinear stochastic differential equations. Previous approaches to the analysis of this system have been based on linearised approximations of the dynamics, which are limited in their ability to capture the inherent nonlinearities in the physiological system. In this paper we present a nonlinear filtering method for simultaneous estimation of the hidden physiological states and the system parameters, based on an iterative coordinate descent framework. State estimates of the cerebral blood flow, cerebral blood volume and deoxyhaemoglobin content are determined using a particle filter, demonstrated via simulation to be accurate, robust and efficient in comparison to linearisation-based techniques. The adaptive state and parameter estimation algorithm generates physiologically reasonable parameter estimates for experimental fMRI data. It is anticipated that signal processing techniques for modelling and estimation will become increasingly important in fMRI analyses as limitations of linear and linearised modelling are reached.
A general analysis of calibrated BOLD methodology for measuring CMRO2 responses: comparison of a new approach with existing methods.
Blockley, Nicholas P; Griffeth, Valerie E M; Buxton, Richard B
The amplitude of the BOLD response to a stimulus is not only determined by changes in cerebral blood flow (CBF) and oxygen metabolism (CMRO(2)), but also by baseline physiological parameters such as haematocrit, oxygen extraction fraction (OEF) and blood volume. The calibrated BOLD approach aims to account for this physiological variation by performing an additional calibration scan. This calibration typically consists of a hypercapnia or hyperoxia respiratory challenge, although we propose that a measurement of the reversible transverse relaxation rate, R(2)', might also be used. A detailed model of the BOLD effect was used to simulate each of the calibration experiments, as well as the activation experiment, whilst varying a number of physiological parameters associated with the baseline state and response to activation. The effectiveness of the different calibration methods was considered by testing whether the BOLD response to activation scaled by the calibration parameter combined with the measured CBF provides sufficient information to reliably distinguish different levels of CMRO(2) response despite underlying physiological variability. In addition the effect of inaccuracies in the underlying assumptions of each technique were tested, e.g. isometabolism during hypercapnia. The three primary findings of the study were: 1) The new calibration method based on R(2)' worked reasonably well, although not as well as the ideal hypercapnia method; 2) The hyperoxia calibration method was significantly worse because baseline haematocrit and OEF must be assumed, and these physiological parameters have a significant effect on the measurements; and 3) the venous blood volume change with activation is an important confounding variable for all of the methods, with the hypercapnia method being the most robust when this is uncertain.
Effect of tolperisone on the resting brain and on evoked responses, an phMRI BOLD study.
Kocsis, Pál; Gajári, Dávid; Deli, Levente; Gőcze, Krisztina Zsedrovitsné; Pozsgay, Zsófia; Tihanyi, Károly
Tolperisone is a voltage gated sodium channel blocker, centrally acting muscle relaxant drug, with a very advantageous side effect profile. Like other sodium channel blockers, it has weak affinity to the resting state and high affinity to the open/inactivated state of the channel. In this paper, its effect on BOLD responses in rat brain were elucidated both on the resting brain and paw stimulation evoked BOLD responses. Tolperisone did not exert any visible effect on resting brain, but strongly inhibited the paw stimulation evoked BOLD responses, showing somewhat higher efficacy in brain areas involved in pain sensation. This finding is in a good agreement with its sodium channel blocking profile. In the resting brain, most of the channels are in resting state. Electric train stimuli of the paw results in over activated neurons, where most sodium channels are in open or inactivated state. These data suggest that the very advantageous profile of tolperisone can be explained by its selective action on open or inactivated sodium channels of over-activated neurons in various brain regions rather than by a selective effect in the spinal cord as suggested previously.
Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.
Towse, Theodore F; Elder, Christopher P; Bush, Emily C; Klockenkemper, Samuel W; Bullock, Jared T; Dortch, Richard D; Damon, Bruce M
Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (TR : 1000 and 2500 ms) to determine the potential of T1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two TR values (3.8 ± 0.9 versus 4.0 ± 0.6% for TR = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.
Toddler Inhibitory Control, Bold Response to Novelty, and Positive Affect Predict Externalizing Symptoms in Kindergarten
Buss, Kristin A.; Kiel, Elizabeth J.; Morales, Santiago; Robinson, Emily
Poor inhibitory control and bold-approach have been found to predict the development of externalizing behavior problems in young children. Less research has examined how positive affect may influence the development of externalizing behavior in the context of low inhibitory control and high approach. We used a multimethod approach to examine how observed toddler inhibitory control, bold-approach, and positive affect predicted externalizing outcomes (observed, adult- and self-reported) in additive and interactive ways at the beginning of kindergarten. 24-month-olds (N = 110) participated in a laboratory visit and 84 were followed up in kindergarten for externalizing behaviors. Overall, children who were low in inhibitory control, high in bold-approach, and low in positive affect at 24-months of age were at greater risk for externalizing behaviors during kindergarten. PMID:25018589
BOLD Granger causality reflects vascular anatomy.
Webb, J Taylor; Ferguson, Michael A; Nielsen, Jared A; Anderson, Jeffrey S
A number of studies have tried to exploit subtle phase differences in BOLD time series to resolve the order of sequential activation of brain regions, or more generally the ability of signal in one region to predict subsequent signal in another region. More recently, such lag-based measures have been applied to investigate directed functional connectivity, although this application has been controversial. We attempted to use large publicly available datasets (FCON 1000, ADHD 200, Human Connectome Project) to determine whether consistent spatial patterns of Granger Causality are observed in typical fMRI data. For BOLD datasets from 1,240 typically developing subjects ages 7-40, we measured Granger causality between time series for every pair of 7,266 spherical ROIs covering the gray matter and 264 seed ROIs at hubs of the brain's functional network architecture. Granger causality estimates were strongly reproducible for connections in a test and replication sample (n=620 subjects for each group), as well as in data from a single subject scanned repeatedly, both during resting and passive video viewing. The same effect was even stronger in high temporal resolution fMRI data from the Human Connectome Project, and was observed independently in data collected during performance of 7 task paradigms. The spatial distribution of Granger causality reflected vascular anatomy with a progression from Granger causality sources, in Circle of Willis arterial inflow distributions, to sinks, near large venous vascular structures such as dural venous sinuses and at the periphery of the brain. Attempts to resolve BOLD phase differences with Granger causality should consider the possibility of reproducible vascular confounds, a problem that is independent of the known regional variability of the hemodynamic response.
A nonlinear BOLD model accounting for refractory effect by applying the longitudinal relaxation in NMR to the linear BOLD model.
Jung, Kwan-Jin
A mathematical model to regress the nonlinear blood oxygen level-dependent (BOLD) fMRI signal has been developed by incorporating the refractory effect into the linear BOLD model of the biphasic gamma variate function. The refractory effect was modeled as a relaxation of two separate BOLD capacities corresponding to the biphasic components of the BOLD signal in analogy with longitudinal relaxation of magnetization in NMR. When tested with the published fMRI data of finger tapping, the nonlinear BOLD model with the refractory effect reproduced the nonlinear BOLD effects such as reduced poststimulus undershoot and saddle pattern in a prolonged stimulation as well as the reduced BOLD signal for repetitive stimulation.
Concordance of Epileptic Networks Associated with Epileptic Spikes Measured by High-Density EEG and Fast fMRI
Jäger, Vera; Dümpelmann, Matthias; LeVan, Pierre; Ramantani, Georgia; Mader, Irina; Schulze-Bonhage, Andreas; Jacobs, Julia
Objective The present study aims to investigate whether a newly developed fast fMRI called MREG (magnetic resonance encephalography) measures metabolic changes related to interictal epileptic discharges (IED). For this purpose BOLD changes are correlated with the IED distribution and variability. Methods Patients with focal epilepsy underwent EEG-MREG using a 64 channel cap. IED voltage maps were generated using 32 and 64 channels and compared regarding their correspondence to the BOLD response. The extents of IEDs (defined as number of channels with >50% of maximum IED negativity) were correlated with the extents of positive and negative BOLD responses. Differences in inter-spike variability were investigated between interictal epileptic discharges (IED) sets with and without concordant positive or negative BOLD responses. Results 17 patients showed 32 separate IED types. In 50% of IED types the BOLD changes could be confirmed by another independent imaging method. The IED extent significantly correlated with the positive BOLD extent (p = 0.04). In 6 patients the 64-channel EEG voltage maps better reflected the positive or negative BOLD response than the 32-channel EEG; in all others no difference was seen. Inter-spike variability was significantly lower in IED sets with than without concordant positive or negative BOLD responses (with p = 0.04). Significance Higher density EEG and fast fMRI seem to improve the value of EEG-fMRI in epilepsy. The correlation of positive BOLD and IED extent could suggest that widespread BOLD responses reflect the IED network. Inter-spike variability influences the likelihood to find IED concordant positive or negative BOLD responses, which is why single IED analysis may be promising. PMID:26496480
Discerning Professional Identity and Becoming Bold, Socially Responsible Teacher-Leaders
ERIC Educational Resources Information Center
Collay, Michelle
This essay reviews the powerful influence of professional identity in shaping how school leaders perceive their work. I review factors that mold teacher professional identity, implications for educational leadership pedagogy, and supports and barriers for teacher leaders to consider in their quest to more fully enact bold, socially responsible…
fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI.
Niranjan, Arun; Christie, Isabel N; Solomon, Samuel G; Wells, Jack A; Lythgoe, Mark F
The use of functional magnetic resonance imaging (fMRI) in mice is increasingly prevalent, providing a means to non-invasively characterise functional abnormalities associated with genetic models of human diseases. The predominant stimulus used in task-based fMRI in the mouse is electrical stimulation of the paw. Task-based fMRI in mice using visual stimuli remains underexplored, despite visual stimuli being common in human fMRI studies. In this study, we map the mouse brain visual system with BOLD measurements at 9.4T using flashing light stimuli with medetomidine anaesthesia. BOLD responses were observed in the lateral geniculate nucleus, the superior colliculus and the primary visual area of the cortex, and were modulated by the flashing frequency, diffuse vs focussed light and stimulus context. Negative BOLD responses were measured in the visual cortex at 10Hz flashing frequency; but turned positive below 5Hz. In addition, the use of interleaved snapshot GE-EPI improved fMRI image quality without diminishing the temporal contrast-noise-ratio. Taken together, this work demonstrates a novel methodological protocol in which the mouse brain visual system can be non-invasively investigated using BOLD fMRI.
Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks
NASA Astrophysics Data System (ADS)
Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas
We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.
BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone.
Moore, Kelsey; Madularu, Dan; Iriah, Sade; Yee, Jason R; Kulkarni, Praveen; Darcq, Emmanuel; Kieffer, Brigitte L; Ferris, Craig F
Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high μ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala, and hypothalamus), and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex, and prelimbic cortex). Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala, and preoptic areas). This result indicates that most effects of OXY on positive BOLD are mediated by the μ opioid receptor (on-target effects). OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122) and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum), and in some case intensified (hippocampus). Negative BOLD analysis therefore shows activation and deactivation events in the absence of the μ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects). Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY brain
BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone
Moore, Kelsey; Madularu, Dan; Iriah, Sade; Yee, Jason R.; Kulkarni, Praveen; Darcq, Emmanuel; Kieffer, Brigitte L.; Ferris, Craig F.
Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high μ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala, and hypothalamus), and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex, and prelimbic cortex). Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala, and preoptic areas). This result indicates that most effects of OXY on positive BOLD are mediated by the μ opioid receptor (on-target effects). OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122) and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum), and in some case intensified (hippocampus). Negative BOLD analysis therefore shows activation and deactivation events in the absence of the μ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects). Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY brain
Area-Specific Information Processing in Prefrontal Cortex during a Probabilistic Inference Task: A Multivariate fMRI BOLD Time Series Analysis
Demanuele, Charmaine; Kirsch, Peter; Esslinger, Christine; Zink, Mathias; Meyer-Lindenberg, Andreas; Durstewitz, Daniel
Introduction Discriminating spatiotemporal stages of information processing involved in complex cognitive processes remains a challenge for neuroscience. This is especially so in prefrontal cortex whose subregions, such as the dorsolateral prefrontal (DLPFC), anterior cingulate (ACC) and orbitofrontal (OFC) cortices are known to have differentiable roles in cognition. Yet it is much less clear how these subregions contribute to different cognitive processes required by a given task. To investigate this, we use functional MRI data recorded from a group of healthy adults during a "Jumping to Conclusions" probabilistic reasoning task. Methods We used a novel approach combining multivariate test statistics with bootstrap-based procedures to discriminate between different task stages reflected in the fMRI blood oxygenation level dependent signal pattern and to unravel differences in task-related information encoded by these regions. Furthermore, we implemented a new feature extraction algorithm that selects voxels from any set of brain regions that are jointly maximally predictive about specific task stages. Results Using both the multivariate statistics approach and the algorithm that searches for maximally informative voxels we show that during the Jumping to Conclusions task, the DLPFC and ACC contribute more to the decision making phase comprising the accumulation of evidence and probabilistic reasoning, while the OFC is more involved in choice evaluation and uncertainty feedback. Moreover, we show that in presumably non-task-related regions (temporal cortices) all information there was about task processing could be extracted from just one voxel (indicating the unspecific nature of that information), while for prefrontal areas a wider multivariate pattern of activity was maximally informative. Conclusions/Significance We present a new approach to reveal the different roles of brain regions during the processing of one task from multivariate activity patterns
Neurophysiological and BOLD signal uncoupling of giant somatosensory evoked potentials in progressive myoclonic epilepsy: a case-series study
Storti, Silvia F.; Del Felice, Alessandra; Canafoglia, Laura; Formaggio, Emanuela; Brigo, Francesco; Alessandrini, Franco; Bongiovanni, Luigi G.; Menegaz, Gloria; Manganotti, Paolo
In progressive myoclonic epilepsy (PME), a rare epileptic syndrome caused by a variety of genetic disorders, the combination of peripheral stimulation and functional magnetic resonance imaging (fMRI) can shed light on the mechanisms underlying cortical dysfunction. The aim of the study is to investigate sensorimotor network modifications in PME by assessing the relationship between neurophysiological findings and blood oxygen level dependent (BOLD) activation. Somatosensory-evoked potential (SSEP) obtained briefly before fMRI and BOLD activation during median-nerve electrical stimulation were recorded in four subjects with typical PME phenotype and compared with normative data. Giant scalp SSEPs with enlarger N20-P25 complex compared to normal data (mean amplitude of 26.2 ± 8.2 μV after right stimulation and 27.9 ± 3.7 μV after left stimulation) were detected. Statistical group analysis showed a reduced BOLD activation in response to median nerve stimulation in PMEs compared to controls over the sensorimotor (SM) areas and an increased response over subcortical regions (p < 0.01, Z > 2.3, corrected). PMEs show dissociation between neurophysiological and BOLD findings of SSEPs (giant SSEP with reduced BOLD activation over SM). A direct pathway connecting a highly restricted area of the somatosensory cortex with the thalamus can be hypothesized to support the higher excitability of these areas. PMID:28294187
Frequency-specific electrocorticographic correlates of working memory delay period fMRI activity.
Khursheed, Faraz; Tandon, Nitin; Tertel, Kathrin; Pieters, Thomas A; Disano, Michael A; Ellmore, Timothy M
Electrocorticography (ECoG) and functional MRI (BOLD-fMRI) have been used previously to measure brain activity during working memory delay periods. These studies have separately reported oscillation changes in the theta (4-8 Hz) band and BOLD-fMRI increases during delay periods when information is maintained in memory. However, it is not known how intracranial cortical field potential (CFP) changes relate to BOLD-fMRI responses during delay periods. To answer this question, fMRI was obtained from six epilepsy patients during a visual working memory task. Then, following subdural macroelectrode implant, continuous ECoG was used to record CFPs during the same task. Time-frequency analyses showed delay period gamma band oscillation amplitude increases on electrodes located near fMRI activity, while in the theta band changes were higher for electrodes located away from fMRI activation. The amplitude of the ECoG gamma band response was significantly positively correlated with the fMRI response, while a negative correlation was found for the theta band. The findings are consistent with previous reports of local field potential (LFP) coupling in the gamma band with BOLD-fMRI responses during visual stimulation in monkeys, but are novel in that the relationship reported here persists after the disappearance of visual stimuli while information is being maintained in memory. We conclude that there is a relationship between BOLD-fMRI increases and human working memory delay period gamma oscillation increases and theta decreases. The spectral profile change provides a basis for comparison of working memory delay period BOLD-fMRI with field potential recordings in animals and other human intracranial EEG studies.
Characterizing response to elemental unit of acoustic imaging noise: an FMRI study.
Tamer, Gregory G; Luh, Wen-Ming; Talavage, Thomas M
Acoustic imaging noise produced during functional magnetic resonance imaging (fMRI) studies can hinder auditory fMRI research analysis by altering the properties of the acquired time-series data. Acoustic imaging noise can be especially confounding when estimating the time course of the hemodynamic response (HDR) in auditory event-related fMRI (fMRI) experiments. This study is motivated by the desire to establish a baseline function that can serve not only as a comparison to other quantities of acoustic imaging noise for determining how detrimental is one's experimental noise, but also as a foundation for a model that compensates for the response to acoustic imaging noise. Therefore, the amplitude and spatial extent of the HDR to the elemental unit of acoustic imaging noise (i.e., a single ping) associated with echoplanar acquisition were characterized and modeled. Results from this fMRI study at 1.5 T indicate that the group-averaged HDR in left and right auditory cortex to acoustic imaging noise (duration of 46 ms) has an estimated peak magnitude of 0.29% (right) to 0.48% (left) signal change from baseline, peaks between 3 and 5 s after stimulus presentation, and returns to baseline and remains within the noise range approximately 8 s after stimulus presentation.
Striatal BOLD Response Reflects the Impact of Herd Information on Financial Decisions
Burke, Christopher J.; Tobler, Philippe N.; Schultz, Wolfram; Baddeley, Michelle
Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI), we scanned participants as they made decisions on whether to buy stocks after observing others' buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants' decisions arising from the observation of other peoples' decisions. The signal did not track non-human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision making and identify a possible neural basis for herd behavior. PMID:20589242
Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience
Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha
Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues. This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574302
Negative BOLD in default-mode structures measured with EEG-MREG is larger in temporal than extra-temporal epileptic spikes
Jacobs, Julia; Menzel, Antonia; Ramantani, Georgia; Körbl, Katharina; Assländer, Jakob; Schulze-Bonhage, Andreas; Hennig, Jürgen; LeVan, Pierre
Introduction: EEG-fMRI detects BOLD changes associated with epileptic interictal discharges (IED) and can identify epileptogenic networks in epilepsy patients. Besides positive BOLD changes, negative BOLD changes have sometimes been observed in the default-mode network, particularly using group analysis. A new fast fMRI sequence called MREG (Magnetic Resonance Encephalography) shows increased sensitivity to detect IED-related BOLD changes compared to the conventional EPI sequence, including frequent occurrence of negative BOLD responses in the DMN. The present study quantifies the concordance between the DMN and negative BOLD related to IEDs of temporal and extra-temporal origin. Methods: Focal epilepsy patients underwent simultaneous EEG-MREG. Areas of overlap were calculated between DMN regions, defined as precuneus, posterior cingulate, bilateral inferior parietal and mesial prefrontal cortices according to a standardized atlas, and significant negative BOLD changes revealed by an event-related analysis based on the timings of IED seen on EEG. Correlation between IED number/lobe of origin and the overlap were calculated. Results: 15 patients were analyzed, some showing IED over more than one location resulting in 30 different IED types. The average overlap between negative BOLD and DMN was significantly larger in temporal (23.7 ± 19.6 cm3) than extra-temporal IEDs (7.4 ± 5.1 cm3, p = 0.008). There was no significant correlation between the number of IEDs and the overlap between DMN structures and negative BOLD areas. Discussion: MREG results in an increased sensitivity to detect negative BOLD responses related to focal IED in single patients, with responses often occurring in DMN regions. In patients with high overlap with the DMN, this suggests that epileptic IEDs may be associated with a brief decrease in attention and cognitive ability. Interestingly this observation was not dependent on the frequency of IED but more common in IED of temporal origin. PMID
How much luxury is there in 'luxury perfusion'? An analysis of the BOLD response in the visual areas V1 and V2.
Marcar, Valentine L; Loenneker, Thomas; Straessle, Andrea; Girard, Franck; Martin, Ernst
We re-analyzed the functional magnetic resonance imaging data from a study involving awake, adult, human volunteers in order to examine the influence of vascular density on the blood oxygenation level-dependent (BOLD) response. We employed a flashed and reversing stimulus paradigm where the latter stimulated twice the number of receptive fields and with it doubled the neuronal metabolic load (CMRO2) compared to the former stimulus. The blood flow increase to these stimuli was identical, so that differences in the BOLD response are due to differences in the oxygen extraction fraction. By comparing the BOLD response in human striate cortex (V1) and its neighbor, extra-striate area V2 to the two stimuli, we were able to determine the influence of the higher vascular density of striate cortex on the BOLD response. In striate cortex, the extent of activation, as measured by the number of activated voxels, was larger for the flashed than for the reversing stimulus. In extra-striate area V2, no such difference in the extent of activation was noted. Gauging the local concentration of HbR using deltaR2*, we found it to be significantly lower for the flashed than for the reversing checkerboard. We estimated the HbR concentration in extra-striate area V2 to be double that of striate cortex independent of the stimulus presented. A frequency distribution of the deltaR2* values for the flashed and reversing checkerboard revealed a shift consistent with an increase in the HbR concentration between areas V1 and V2. The metabolically most demanding stimulus, the reversing checkerboard was associated with the highest HbR concentration and with the largest number of voxels with a negative BOLD response.
BOLD response to motion verbs in left posterior middle temporal gyrus during story comprehension.
Wallentin, Mikkel; Nielsen, Andreas Højlund; Vuust, Peter; Dohn, Anders; Roepstorff, Andreas; Lund, Torben Ellegaard
A primary focus within neuroimaging research on language comprehension is on the distribution of semantic knowledge in the brain. Studies have shown that the left posterior middle temporal gyrus (LPMT), a region just anterior to area MT/V5, is important for the processing of complex action knowledge. It has also been found that motion verbs cause activation in LPMT. In this experiment we investigated whether this effect could be replicated in a setting resembling real life language comprehension, i.e. without any overt behavioral task during passive listening to a story. During fMRI participants listened to a recording of the story "The Ugly Duckling". We incorporated a nuisance elimination regression approach for factoring out known nuisance variables both in terms of physiological noise, sound intensity, linguistic variables and emotional content. Compared to the remaining text, clauses containing motion verbs were accompanied by a robust activation of LPMT with no other significant effects, consistent with the hypothesis that this brain region is important for processing motion knowledge, even during naturalistic language comprehension conditions.
Predicting goals in action episodes attenuates BOLD response in inferior frontal and occipitotemporal cortex.
Wurm, Moritz F; Hrkać, Mari; Morikawa, Yuka; Schubotz, Ricarda I
Actions are usually made of several action steps gearing towards an overarching goal. During observation of such action episodes the overarching action goal becomes more and more clear and upcoming action steps can be predicted with increasing precision. To tap this process, the present fMRI study investigated the dynamic changes of neural activity during the observation of distinct action steps that cohere by an overarching goal. Our hypotheses specifically addressed the role of the inferior frontal gyrus (IFG), a region assumed to be a key hub for integration functions during action processing, as well as the role of regions involved in action perception (often referred to as action observation network or AON) that should benefit from the predictability of forthcoming action steps. Participants watched separate action steps that formed a coherent action goal or not (factor goal coherence) and were performed by a single actor or not (factor actor coherence). Independent of actor coherence, neural activity in IFG and occipitotemporal cortex decreased as a function of goal predictability during the unfolding of goal-coherent episodes. In addition, we identified a network (precuneus, dorsolateral prefrontal and orbitofrontal cortex, angular gyrus, and middle temporal gyrus) that showed increased activity for goal coherence. We conclude that IFG fosters the integration of action steps to build overarching goals. Identifying the unifying goal of an action episode allows anticipation, and thus efficient processing, of forthcoming action steps. To this end, past action steps of the action episode are buffered and recollected with recourse to episodic memory.
Effects of Family History of Alcohol Use Disorders on Spatial Working Memory BOLD Response in Adolescents
Spadoni, Andrea D.; Norman, Andria L.; Schweinsburg, Alecia D.; Tapert, Susan F.
Background A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission. Methods We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years. Results Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p = 0.03), and a trend for more relative activity during rest (β = −0.25, p = 0.07) in this cluster. Conclusions Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence. PMID:18540914
The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study.
Ely, Alice V; Childress, Anna Rose; Jagannathan, Kanchana; Lowe, Michael R
Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food.
Paradigm-free mapping with morphological component analysis: getting most out of fMRI data
NASA Astrophysics Data System (ADS)
Caballero Gaudes, César; Van De Ville, Dimitri; Petridou, Natalia; Lazeyras, François; Gowland, Penny
Functional magnetic resonance imaging (fMRI) is a non-invasive imaging technique that maps the brain's response to neuronal activity based on the blood oxygenation level dependent (BOLD) effect. This work proposes a novel method for fMRI data analysis that enables the decomposition of the fMRI signal in its sources based on morphological descriptors. Beyond traditional fMRI hypothesis-based or blind data-driven exploratory approaches, this method allows the detection of BOLD responses without prior timing information. It is based on the deconvolution of the neuronal-related haemodynamic component of the fMRI signal with paradigm free mapping and also furnishes estimates of the movement-related effects, instrumental drifts and physiological fluctuations. Our algorithm is based on an overcomplete representation of the fMRI voxel time series with an additive linear model that is recovered by means of a L1-norm regularized least-squares estimators and an adapted block coordinate relaxation procedure. The performance of the technique is evaluated with simulated data and real experimental data acquired at 3T.
Replicability and Heterogeneity of Awake Unrestrained Canine fMRI Responses
Berns, Gregory S.; Brooks, Andrew; Spivak, Mark
Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs. PMID:24324719
Does Chronic Tinnitus Alter the Emotional Response Function of the Amygdala?: A Sound-Evoked fMRI Study
Davies, Jeff E.; Gander, Phillip E.; Hall, Deborah A.
Tinnitus is often associated with strong negative thoughts and emotions which can contribute to a distressing and chronic long-term condition. The amygdala, the "feeling and reacting" part of the brain, may play a key role in this process. Although implicated in several theoretical models of tinnitus, quantification of activity in the human amygdala has only been made possible more recently through neuroimaging methods such as functional magnetic resonance imaging (fMRI) but benefits from modified scanning parameters using a double-echo acquisition for improved BOLD sensitivity. This study thus examined the role of the amygdala in emotional sound processing in people with tinnitus using a novel double-echo imaging sequence for optimal detectability of subcortical activity. Our hypotheses were: (1) emotionally evocative sound clips rated as pleasant or unpleasant would elicit stronger amygdalar activation than sound clips rated as neutral, (2) people with tinnitus have greater amygdalar activation in response to emotionally evocative sounds (relative to neutral sounds) compared to controls. Methods: Twelve participants all with chronic, constant tinnitus took part. We also recruited 11 age and hearing-matched controls. Participants listened to a range of emotionally evocative sound clips; rated as pleasant, unpleasant or neutral. A region-of-interest analysis was chosen to test our a priori hypotheses. Results: Both groups displayed a robust and similar overall response to sounds vs. silence in the following ascending auditory pathways; inferior colliculus, medial geniculate body and the primary auditory cortex. In support of our first hypothesis, the amygdala's response to pleasant and unpleasant sound clips was significantly greater than neutral sounds. Opposing our second hypothesis, we found that the amygdala's overall response to pleasant and unpleasant sounds (compared to neutral sounds) was actually lower in the tinnitus group as compared to the controls
Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation.
Plichta, Michael M; Wolf, Isabella; Hohmann, Sarah; Baumeister, Sarah; Boecker, Regina; Schwarz, Adam J; Zangl, Maria; Mier, Daniela; Diener, Carsten; Meyer, Patric; Holz, Nathalie; Ruf, Matthias; Gerchen, Martin F; Bernal-Casas, David; Kolev, Vasil; Yordanova, Juliana; Flor, Herta; Laucht, Manfred; Banaschewski, Tobias; Kirsch, Peter; Meyer-Lindenberg, Andreas; Brandeis, Daniel
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.
Investigations on spinal cord fMRI of cats under ketamine.
Cohen-Adad, J; Hoge, R D; Leblond, H; Xie, G; Beaudoin, G; Song, A W; Krueger, G; Doyon, J; Benali, H; Rossignol, S
Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response.
Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory.
Michels, Lars; Lüchinger, Rafael; Koenig, Thomas; Martin, Ernst; Brandeis, Daniel
In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that
Single stimulus fMRI produces a neural individual difference measure for Autism Spectrum Disorder.
Lu, James; Kishida, Ken; De Asis Cruz, Josepheen; Lohrenz, Terry; Deering, Diane Treadwell; Beauchamp, Michael; Montague, P Read
Functional magnetic resonance imaging typically makes inferences about neural substrates of cognitive phenomena at the group level. We report the use of a single-stimulus BOLD response in the cingulate cortex that differentiates individual children with autism spectrum disorder from matched typically developing control children with sensitivity and specificity of 63.6% and 73.7% respectively. The approach consists of passive viewing of 'self' and 'other' faces from which an individual difference measure is derived from the BOLD response to the first 'self' image only; the method, penalized logistic regression, requires no averaging over stimulus presentations or individuals. These findings show that single-stimulus fMRI responses can be extracted from individual subjects and used profitably as a neural individual difference measure. The result suggests that single-stimulus fMRI can be developed to produce quantitative neural biomarkers for other developmental disorders and may even be useful in the rapid typing of cognition in healthy individuals.
Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: an fMRI study.
Atalayer, Deniz; Pantazatos, Spiro P; Gibson, Charlisa D; McOuatt, Haley; Puma, Lauren; Astbury, Nerys M; Geliebter, Allan
Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women.
Incongruent abstract stimulus-response bindings result in response interference: FMRI and EEG evidence from visual object classification priming.
Horner, Aidan J; Henson, Richard N
Stimulus repetition often leads to facilitated processing, resulting in neural decreases (repetition suppression) and faster RTs (repetition priming). Such repetition-related effects have been attributed to the facilitation of repeated cognitive processes and/or the retrieval of previously encoded stimulus-response (S-R) bindings. Although previous research has dissociated these two forms of learning, their interaction in the brain is not fully understood. Utilizing the spatial and temporal resolutions of fMRI and EEG, respectively, we examined a long-lag classification priming paradigm that required response repetitions or reversals at multiple levels of response representation. We found a repetition effect in occipital/temporal cortex (fMRI) that was time-locked to stimulus onset (EEG) and robust to switches in response, together with a repetition effect in inferior pFC (fMRI) that was time-locked to response onset (EEG) and sensitive to switches in response. The response-sensitive effect occurred even when changing from object names (words) to object pictures between repetitions, suggesting that S-R bindings can code abstract representations of stimuli. Most importantly, we found evidence for interference effects when incongruent S-R bindings were retrieved, with increased neural activity in inferior pFC, demonstrating that retrieval of S-R bindings can result in facilitation or interference, depending on the congruency of response between repetitions.
Abstinent adolescent marijuana users show altered fMRI response during spatial working memory☆
Schweinsburg, Alecia D.; Nagel, Bonnie J.; Schweinsburg, Brian C.; Park, Ann; Theilmann, Rebecca J.; Tapert, Susan F.
Marijuana is the most widely used illicit substance among teenagers, yet little is known about the possible neural influence of heavy marijuana use during adolescence. We previously demonstrated an altered functional magnetic resonance imaging (fMRI) activity related to spatial working memory (SWM) among adolescents who were heavy users of after an average of 8 days of abstinence, but the persisting neural effects remain unclear. To characterize the potentially persisting neurocognitive effects of heavy marijuana use in adolescence, we examined fMRI response during SWM among abstinent marijuana-using teens. Participants were 15 MJ teens and 17 demographically similar non-using controls, ages 16–18. Teens underwent biweekly urine toxicology screens to ensure abstinence for 28 days before fMRI acquisition. Groups performed similarly on the SWM task, but MJ teens demonstrated lower activity in right dorsolateral prefrontal and occipital cortices, yet significantly more activation in right posterior parietal cortex. MJ teens showed abnormalities in brain response during a SWM task compared with controls, even after 1 month of abstinence. The activation pattern among MJ teens may reflect different patterns of utilization of spatial rehearsal and attention strategies, and could indicate altered neurodevelopment or persisting abnormalities associated with heavy marijuana use in adolescence. PMID:18356027
Single-trial coupling of EEG and fMRI reveals the involvement of early anterior cingulate cortex activation in effortful decision making.
Mulert, Christoph; Seifert, Christian; Leicht, Gregor; Kirsch, Valerie; Ertl, Matthias; Karch, Susanne; Moosmann, Matthias; Lutz, Jürgen; Möller, Hans-Jürgen; Hegerl, Ulrich; Pogarell, Oliver; Jäger, Lorenz
While the precise role of the anterior cingulate cortex (ACC) is still being discussed, it has been suggested that ACC activity might reflect the amount of mental effort associated with cognitive processing. So far, not much is known about the temporal dynamics of ACC activity in effort-related decision making or auditory attention, because fMRI is limited concerning its temporal resolution and electroencephalography (EEG) is limited concerning its spatial resolution. Single-trial coupling of EEG and fMRI can be used to predict the BOLD signal specifically related to amplitude variations of electrophysiological components. The striking feature of single-trial coupling is its ability to separate different aspects of the BOLD signal according to their specific relationship to a distinct neural process. In the present study we investigated 10 healthy subjects with a forced choice reaction task under both low and high effort conditions and a control condition (passive listening) using simultaneous EEG and fMRI. We detected a significant effect of mental effort only for the N1 potential, but not for the P300 potential. In the fMRI analysis, ACC activation was present only in the high effort condition. We used single-trial coupling of EEG and fMRI in order to separate information specific to N1-amplitude variations from the unrelated BOLD response. Under high effort conditions we were able to detect circumscribed BOLD activations specific to the N1 potential in the ACC (t=4.7) and the auditory cortex (t=6.1). Comparing the N1-specific BOLD activity of the high effort condition versus the control condition we found only activation of the ACC (random effects analysis, corrected for multiple comparisons, t=4.4). These findings suggest a role of early ACC activation in effort-related decision making and provide a direct link between the N1 component and its corresponding BOLD signal.
Decreased sleep duration is associated with increased fMRI responses to emotional faces in children.
Reidy, Brooke L; Hamann, Stephan; Inman, Cory; Johnson, Katrina C; Brennan, Patricia A
In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation.
Photosynthesis and growth responses of mustard (Brassica juncea L. cv Pusa Bold) plants to free air carbon dioxide enrichment (FACE).
Ruhil, Kamal; Sheeba; Ahmad, Altaf; Iqbal, Muhammad; Tripathy, Baishnab C
Increased atmospheric [CO2] is likely to affect photosynthesis, plant growth, and yield potential of plants. Mustard (Brassica juncea L.) is an important oil seed crop that is widely grown in India. Therefore, the impact of elevated [CO2] (585 μmol mol(-1)) on pigment and protein content, chlorophyll a fluorescence, photosynthetic electron transport reactions, CO2 assimilation, biomass production, and seed yield potential was measured in B. juncea cv Pusa Bold, grown inside free air carbon dioxide enrichment (FACE) rings installed on the campus of Jawaharlal Nehru University, New Delhi, India. Plants were grown for three consecutive winter seasons (2010-2013), in ambient (385 μmol mol(-1)) or elevated [CO2], in field conditions. Elevated [CO2] had no significant effect on the minimal chlorophyll fluorescence (F 0), while the quantum efficiency of Photosystem II, measured as variable fluorescence (F v = F m-F 0) to maximum fluoresence (F m), increased by 3 %. Electron transport rate, photosystem I, photosystem II, and whole chain electron transport rates increased by 8 % in elevated [CO2]. However, the net photosynthesis rate increased by ≈50 % in three growing seasons under elevated [CO2] condition. The stomatal conductance and transpiration rate decreased resulting in higher photosynthetic water use efficiency. The photosynthesizing surface, i.e., leaf area index substantially increased leading to higher biomass and seed yield under elevated [CO2] condition. Acclimatory downregulation of photosynthesis and plant productivity was not observed in three consecutive growing years suggesting that in the absence of nutrient limitation, B. juncea is highly responsive to elevated CO2 whose yield potential shall increase in changing climatic conditions.
Enhanced Thalamic Functional Connectivity with No fMRI Responses to Affected Forelimb Stimulation in Stroke-Recovered Rats
Shim, Woo H.; Suh, Ji-Yeon; Kim, Jeong K.; Jeong, Jaeseung; Kim, Young R.
Neurological recovery after stroke has been extensively investigated to provide better understanding of neurobiological mechanism, therapy, and patient management. Recent advances in neuroimaging techniques, particularly functional MRI (fMRI), have widely contributed to unravel the relationship between the altered neural function and stroke-affected brain areas. As results of previous investigations, the plastic reorganization and/or gradual restoration of the hemodynamic fMRI responses to neural stimuli have been suggested as relevant mechanisms underlying the stroke recovery process. However, divergent study results and modality-dependent outcomes have clouded the proper interpretation of variable fMRI signals. Here, we performed both evoked and resting state fMRI (rs-fMRI) to clarify the link between the fMRI phenotypes and post-stroke functional recovery. The experiments were designed to examine the altered neural activity within the contra-lesional hemisphere and other undamaged brain regions using rat models with large unilateral stroke, which despite the severe injury, exhibited nearly full recovery at ∼6 months after stroke. Surprisingly, both blood oxygenation level-dependent and blood volume-weighted (CBVw) fMRI activities elicited by electrical stimulation of the stroke-affected forelimb were completely absent, failing to reveal the neural origin of the behavioral recovery. In contrast, the functional connectivity maps showed highly robust rs-fMRI activity concentrated in the contra-lesional ventromedial nucleus of thalamus (VM). The negative finding in the stimuli-induced fMRI study using the popular rat middle cerebral artery model denotes weak association between the fMRI hemodynamic responses and neurological improvement. The results strongly caution the indiscreet interpretation of stroke-affected fMRI signals and demonstrate rs-fMRI as a complementary tool for efficiently characterizing stroke recovery. PMID:28119575
Impaired fMRI activation in patients with primary brain tumors.
Jiang, Zhen; Krainik, Alexandre; David, Olivier; Salon, Caroline; Troprès, Irène; Hoffmann, Dominique; Pannetier, Nicolas; Barbier, Emmanuel L; Bombìn, Eduardo Ramos; Warnking, Jan; Pasteris, Caroline; Chabardes, Stefan; Berger, François; Grand, Sylvie; Segebarth, Christoph; Gay, Emmanuel; Le Bas, Jean-François
To characterize peritumoral BOLD contrast disorders, 25 patients referred for resection of primary frontal or parietal neoplasms (low-grade glioma (LGG) (n=8); high-grade glioma (HGG) (n=7); meningioma (n=10)) without macroscopic tumoral infiltration of the primary sensorimotor cortex (SM1) were examined preoperatively using BOLD fMRI during simple motor tasks. Overall cerebral BOLD signal was estimated using vasoreactivity to carbogen inhalation. Using bolus of gadolinium, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were estimated. In a 1cm(3) region-of-interest centered on maximal T-value in SM1 contralateral to movements, interhemispheric asymmetry was evaluated using interhemispheric ratios for BOLD and perfusion parameters. During motor tasks contralateral to the tumor, ipsitumoral sensorimotor activations were decreased in HGG and meningiomas, correlated to the distance between the tumor and SM1. Whereas CBV was decreased in ipsitumoral SM1 for HGG, it remained normal in meningiomas. Changes in basal perfusion could not explain motor activation impairment in SM1. Decreased interhemispheric ratio of the BOLD response to carbogen was the best predictor to model the asymmetry of motor activation (R=0.51). Moreover, 94.9+/-4.9% of all motor activations overlapped significant BOLD response to carbogen inhalation.
Coupling Mechanism and Significance of the BOLD Signal: A Status Report
Hillman, Elizabeth M.C.
Functional magnetic resonance imaging (fMRI) provides a unique view of the working human mind. The blood-oxygen-level-dependent (BOLD) signal, detected in fMRI, reflects changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation, which are coupled to underlying neuronal activity by a process termed neurovascular coupling. Over the past 10 years, a range of cellular mechanisms, including astrocytes, pericytes, and interneurons, have been proposed to play a role in functional neurovascular coupling. However, the field remains conflicted over the relative importance of each process, while key spatiotemporal features of BOLD response remain unexplained. Here, we review current candidate neurovascular coupling mechanisms and propose that previously overlooked involvement of the vascular endothelium may provide a more complete picture of how blood flow is controlled in the brain. We also explore the possibility and consequences of conditions in which neurovascular coupling may be altered, including during postnatal development, pathological states, and aging, noting relevance to both stimulus-evoked and resting-state fMRI studies. PMID:25032494
Resting BOLD fluctuations in the primary somatosensory cortex correlate with tactile acuity.
Haag, Lauren M; Heba, Stefanie; Lenz, Melanie; Glaubitz, Benjamin; Höffken, Oliver; Kalisch, Tobias; Puts, Nicholaas A; Edden, Richard A E; Tegenthoff, Martin; Dinse, Hubert; Schmidt-Wilcke, Tobias
Sensory perception, including 2-point discrimination (2 ptD), is tightly linked to cortical processing of tactile stimuli in primary somatosensory cortices. While the role of cortical activity in response to a tactile stimulus has been widely investigated, the role of baseline cortical activity is largely unknown. Using resting state fMRI we investigated the relationship between local BOLD fluctuations in the primary somatosensory cortex (the representational field of the hand) and 2 ptD of the corresponding index finger (right and left). Cortical activity was measured using fractional amplitudes of the low frequency BOLD fluctuations (fALFF) and synchronicity using regional homogeneity (ReHo) of the S1 hand region during rest. 2 ptD correlated with higher ReHo values in the representational areas of the contralateral S1 cortex (left hand: p = .028; right hand: p = .049). 2 ptD additionally correlated with higher fALFF in the representational area of the left hand (p = .007) and showed a trend for a significant correlation in the representational area of the right hand (p = .051). Thus, higher BOLD amplitudes and synchronicity at rest, as measures of cortical activity and synchronicity, respectively, are related to better tactile discrimination abilities of the contralateral hand. Our findings extend the relationship seen between spontaneous BOLD fluctuations and sensory perception.
A signal subspace approach for modeling the hemodynamic response function in fMRI.
Hossein-Zadeh, Gholam-Ali; Ardekani, Babak A; Soltanian-Zadeh, Hamid
Many fMRI analysis methods use a model for the hemodynamic response function (HRF). Common models of the HRF, such as the Gaussian or Gamma functions, have parameters that are usually selected a priori by the data analyst. A new method is presented that characterizes the HRF over a wide range of parameters via three basis signals derived using principal component analysis (PCA). Covering the HRF variability, these three basis signals together with the stimulation pattern define signal subspaces which are applicable to both linear and nonlinear modeling and identification of the HRF and for various activation detection strategies. Analysis of simulated fMRI data using the proposed signal subspace showed increased detection sensitivity compared to the case of using a previously proposed trigonometric subspace. The methodology was also applied to activation detection in both event-related and block design experimental fMRI data using both linear and nonlinear modeling of the HRF. The activated regions were consistent with previous studies, indicating the ability of the proposed approach in detecting brain activation without a priori assumptions about the shape parameters of the HRF. The utility of the proposed basis functions in identifying the HRF is demonstrated by estimating the HRF in different activated regions.
Effects of prenatal marijuana on response inhibition: an fMRI study of young adults.
Smith, Andra M; Fried, Peter A; Hogan, Matthew J; Cameron, Ian
The neurophysiological effects of prenatal marijuana exposure on response inhibition were assessed in 18- to 22-year-olds. Thirty-one participants from the Ottawa Prenatal Prospective Study (OPPS) performed a blocked design Go/No-Go task while neural activity was imaged with functional magnetic resonance imaging (fMRI). The OPPS is a longitudinal study that provides a unique body of information collected from each participant over 20 years, including prenatal drug history, detailed cognitive/behavioral performance from infancy to young adulthood, and current and past drug usage. The fMRI results showed that with increased prenatal marijuana exposure, there was a significant increase in neural activity in bilateral prefrontal cortex and right premotor cortex during response inhibition. There was also an attenuation of activity in left cerebellum with increased prenatal exposure to marijuana when challenging the response inhibition neural circuitry. Prenatally exposed offspring had significantly more commission errors than nonexposed participants, but all participants were able to perform the task with more than 85% accuracy. These findings were observed when controlling for present marijuana use and prenatal exposure to nicotine, alcohol and caffeine, and suggest that prenatal marijuana exposure is related to changes in neural activity during response inhibition that last into young adulthood.
Simultaneous Acquisition of Gradient Echo / Spin Echo BOLD and Perfusion with a Separate Labeling Coil
Glielmi, C.B.; Xu, Q.; Craddock, R.C.; Hu, X.
Arterial spin labeling (ASL) based cerebral blood flow (CBF) imaging complements blood oxygenation level dependent (BOLD) imaging with a measure that is more quantitative and has better specificity to neuronal activation. Relative to gradient echo (GE) BOLD, spin echo (SE) BOLD has better spatial specificity because it is less biased to large draining veins. While there have been many studies comparing simultaneously acquired CBF data with GE BOLD data in fMRI, there have been few studies comparing CBF with SE BOLD and no study comparing all three. We present a pulse sequence that simultaneously acquires CBF data with a separate labeling coil, GE BOLD and SE BOLD images. Simultaneous acquisition avoids inter-scan variability, allowing more direct assessment and comparison of each contrast's relative specificity and reproducibility. Furthermore, it facilitates studies that may benefit from multiple complementary measures. PMID:20648682
Assessment of rodent brain activity using combined [(15)O]H2O-PET and BOLD-fMRI.
Wehrl, Hans F; Martirosian, Petros; Schick, Fritz; Reischl, Gerald; Pichler, Bernd J
The study of brain activation in small animals is of high interest for neurological research. In this study, we proposed a protocol to monitor brain activation in rats following whisker stimulation using the short half-life PET tracer [(15)O]H2O as a marker for cerebral blood flow. This technique enables the study of baseline and activation conditions in fast succession within the same scanning session. Furthermore, we compared the results obtained from PET imaging with additional BOLD-fMRI data acquired in the same animals within the same anesthetic session in immediate succession. Although the maximum relative signal changes during brain activity observed with PET were substantially higher compared to the BOLD-fMRI results, statistical analyses showed that the number of activated voxels in PET was lower compared to the fMRI measurements. Furthermore, there was a difference in the activation centers in both the shape and location between PET and fMRI. The discrepancy in the number of activated voxels could be attributed to a lower overall contrast-to-noise ratio of the PET images compared to BOLD-fMRI, whereas the difference in the spatial location indicates a more fundamental process, involving the different physiological origins of the PET and BOLD-fMRI response. This study clearly demonstrates that [(15)O]H2O-PET activation studies may be performed in small laboratory animals, and shows the complementary nature of studying brain activation using [(15)O]H2O-PET and fMRI.
Brain responses to facial attractiveness induced by facial proportions: evidence from an fMRI study.
Shen, Hui; Chau, Desmond K P; Su, Jianpo; Zeng, Ling-Li; Jiang, Weixiong; He, Jufang; Fan, Jintu; Hu, Dewen
Brain responses to facial attractiveness induced by facial proportions are investigated by using functional magnetic resonance imaging (fMRI), in 41 young adults (22 males and 19 females). The subjects underwent fMRI while they were presented with computer-generated, yet realistic face images, which had varying facial proportions, but the same neutral facial expression, baldhead and skin tone, as stimuli. Statistical parametric mapping with parametric modulation was used to explore the brain regions with the response modulated by facial attractiveness ratings (ARs). The results showed significant linear effects of the ARs in the caudate nucleus and the orbitofrontal cortex for all of the subjects, and a non-linear response profile in the right amygdala for only the male subjects. Furthermore, canonical correlation analysis was used to learn the most relevant facial ratios that were best correlated with facial attractiveness. A regression model on the fMRI-derived facial ratio components demonstrated a strong linear relationship between the visually assessed mean ARs and the predictive ARs. Overall, this study provided, for the first time, direct neurophysiologic evidence of the effects of facial ratios on facial attractiveness and suggested that there are notable gender differences in perceiving facial attractiveness as induced by facial proportions.
Brain responses to facial attractiveness induced by facial proportions: evidence from an fMRI study
Shen, Hui; Chau, Desmond K. P.; Su, Jianpo; Zeng, Ling-Li; Jiang, Weixiong; He, Jufang; Fan, Jintu; Hu, Dewen
Brain responses to facial attractiveness induced by facial proportions are investigated by using functional magnetic resonance imaging (fMRI), in 41 young adults (22 males and 19 females). The subjects underwent fMRI while they were presented with computer-generated, yet realistic face images, which had varying facial proportions, but the same neutral facial expression, baldhead and skin tone, as stimuli. Statistical parametric mapping with parametric modulation was used to explore the brain regions with the response modulated by facial attractiveness ratings (ARs). The results showed significant linear effects of the ARs in the caudate nucleus and the orbitofrontal cortex for all of the subjects, and a non-linear response profile in the right amygdala for only the male subjects. Furthermore, canonical correlation analysis was used to learn the most relevant facial ratios that were best correlated with facial attractiveness. A regression model on the fMRI-derived facial ratio components demonstrated a strong linear relationship between the visually assessed mean ARs and the predictive ARs. Overall, this study provided, for the first time, direct neurophysiologic evidence of the effects of facial ratios on facial attractiveness and suggested that there are notable gender differences in perceiving facial attractiveness as induced by facial proportions. PMID:27779211
Effects of age on negative BOLD signal changes in the primary somatosensory cortex.
Gröschel, Sonja; Sohns, Jan Martin; Schmidt-Samoa, Carsten; Baudewig, Jürgen; Becker, Lars; Dechent, Peter; Kastrup, Andreas
In addition to a contralateral activation of the primary and secondary somatosensory cortices, peripheral sensory stimulation has been shown to elicit responses in the ipsilateral primary somatosensory cortex (SI). In particular, evidence is accumulating that processes of interhemispheric inhibition as depicted by negative blood oxygenation level dependent (BOLD) signal changes are part of somatosensory processes. The aim of the study was to analyze age-related differences in patterns of cerebral activation in the somatosensory system in general and processes of interhemispheric inhibition in particular. For this, a functional magnetic resonance imaging (fMRI) study was performed including 14 younger (mean age 23.3±0.9years) and 13 healthy older participants (mean age 73.2±8.3years). All subjects were scanned during peripheral electrical median nerve stimulation (40Hz) to obtain BOLD responses in the somatosensory system. Moreover, the individual current perception threshold (CPT) as a quantitative measure of sensory function was determined in a separate psychophysical testing. Significant increases in BOLD signal across the entire group could be measured within the contralateral SI, in the bilateral secondary somatosensory cortex (SII), the contralateral supplementary motor area and the insula. Negative BOLD signal changes were delineated in ipsilateral SI/MI as well as in the ipsilateral thalamus and basal ganglia. After comparing the two groups, only the cortical deactivation in ipsilateral SI in the early stimulation phase as well as the activation in contralateral SI and SII in the late stimulation block remained as statistically significant differences between the two groups. The psychophysical experiments yielded a significant age-dependent effect of CPT change with less difference in the older group which is in line with the significantly smaller alterations in maximal BOLD signal change in the contra- and ipsilateral SI found between the two groups
A decomposition model and voxel selection framework for fMRI analysis to predict neural response of visual stimuli.
Raut, Savita V; Yadav, Dinkar M
This paper presents an fMRI signal analysis methodology using geometric mean curve decomposition (GMCD) and mutual information-based voxel selection framework. Previously, the fMRI signal analysis has been conducted using empirical mean curve decomposition (EMCD) model and voxel selection on raw fMRI signal. The erstwhile methodology loses frequency component, while the latter methodology suffers from signal redundancy. Both challenges are addressed by our methodology in which the frequency component is considered by decomposing the raw fMRI signal using geometric mean rather than arithmetic mean and the voxels are selected from EMCD signal using GMCD components, rather than raw fMRI signal. The proposed methodologies are adopted for predicting the neural response. Experimentations are conducted in the openly available fMRI data of six subjects, and comparisons are made with existing decomposition models and voxel selection frameworks. Subsequently, the effect of degree of selected voxels and the selection constraints are analyzed. The comparative results and the analysis demonstrate the superiority and the reliability of the proposed methodology.
A neural correlate of visceral emotional responses: evidence from fMRI of the thoracic spinal cord
Smith, Stephen D.; McIver, Theresa A.
Functional magnetic resonance imaging (fMRI) of thoracic spinal cord neurons was used to examine the neural correlates of visceral emotional responses. Participants completed four spinal fMRI runs involving passive viewing (i.e. no movement) and motoric responses to negative or neutral images. Negative images, particularly in the movement condition, elicited robust activity in motoric nuclei, indicating 'action preparedness'. These images also enhanced activity in autonomic and sensory nuclei, thus providing a clear neural representation of visceral responses to emotional stimuli. PMID:24993101
Altered Dynamics of the fMRI Response to Faces in Individuals with Autism
ERIC Educational Resources Information Center
Kleinhans, Natalia M.; Richards, Todd; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth
Abnormal fMRI habituation in autism spectrum disorders (ASDs) has been proposed as a critical component in social impairment. This study investigated habituation to fearful faces and houses in ASD and whether fMRI measures of brain activity discriminate between ASD and typically developing (TD) controls. Two identical fMRI runs presenting masked…
Response inhibition among early adolescents prenatally exposed to tobacco: An fMRI study
Bennett, David S.; Mohamed, Feroze B.; Carmody, Dennis P.; Bendersky, Margaret; Patel, Sunil; Khorrami, Maryam; Faro, Scott H.; Lewis, Michael
Children prenatally exposed to tobacco have been found to exhibit increased rates of behavior problems related to response inhibition deficits. The present study compared the brain function of tobacco-exposed (n = 7) and unexposed (n = 11) 12-year-olds during a Go/No-Go response inhibition task using an event-related functional MRI (fMRI) design. Prenatal alcohol exposure, neonatal medical problems, environmental risk, IQ, current environmental smoke exposure, and handedness were statistically controlled. Tobacco-exposed children showed greater activation in a relatively large and diverse set of regions, including left frontal, right occipital, and bilateral temporal, and parietal regions. In contrast, unexposed but not exposed children showed activation in the cerebellum, which prior research has indicated is important for attention and motor preparation. The diversity of regions showing greater activation among tobacco-exposed children suggests that their brain function is characterized by an inefficient recruitment of regions required for response inhibition. PMID:19351556
Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering
Havlicek, Martin; Friston, Karl J.; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D.
This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain. PMID:21396454
Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering.
Havlicek, Martin; Friston, Karl J; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D
This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain.
Identifying Core Affect in Individuals from fMRI Responses to Dynamic Naturalistic Audiovisual Stimuli.
Kim, Jongwan; Wang, Jing; Wedell, Douglas H; Shinkareva, Svetlana V
Recent research has demonstrated that affective states elicited by viewing pictures varying in valence and arousal are identifiable from whole brain activation patterns observed with functional magnetic resonance imaging (fMRI). Identification of affective states from more naturalistic stimuli has clinical relevance, but the feasibility of identifying these states on an individual trial basis from fMRI data elicited by dynamic multimodal stimuli is unclear. The goal of this study was to determine whether affective states can be similarly identified when participants view dynamic naturalistic audiovisual stimuli. Eleven participants viewed 5s audiovisual clips in a passive viewing task in the scanner. Valence and arousal for individual trials were identified both within and across participants based on distributed patterns of activity in areas selectively responsive to audiovisual naturalistic stimuli while controlling for lower level features of the stimuli. In addition, the brain regions identified by searchlight analyses to represent valence and arousal were consistent with previously identified regions associated with emotion processing. These findings extend previous results on the distributed representation of affect to multimodal dynamic stimuli.
Identifying Core Affect in Individuals from fMRI Responses to Dynamic Naturalistic Audiovisual Stimuli
Kim, Jongwan; Wang, Jing; Wedell, Douglas H.
Recent research has demonstrated that affective states elicited by viewing pictures varying in valence and arousal are identifiable from whole brain activation patterns observed with functional magnetic resonance imaging (fMRI). Identification of affective states from more naturalistic stimuli has clinical relevance, but the feasibility of identifying these states on an individual trial basis from fMRI data elicited by dynamic multimodal stimuli is unclear. The goal of this study was to determine whether affective states can be similarly identified when participants view dynamic naturalistic audiovisual stimuli. Eleven participants viewed 5s audiovisual clips in a passive viewing task in the scanner. Valence and arousal for individual trials were identified both within and across participants based on distributed patterns of activity in areas selectively responsive to audiovisual naturalistic stimuli while controlling for lower level features of the stimuli. In addition, the brain regions identified by searchlight analyses to represent valence and arousal were consistent with previously identified regions associated with emotion processing. These findings extend previous results on the distributed representation of affect to multimodal dynamic stimuli. PMID:27598534
The Influence of Recency of Use on fMRI Response During Spatial Working Memory in Adolescent Marijuana Users
Schweinsburg, Alecia D.; Schweinsburg, Brian C.; Medina, Krista Lisdahl; McQueeny, Tim; Brown, Sandra A.; Tapert, Susan F.
Some neurocognitive recovery occurs within a month of abstinence from heavy marijuana use, yet functional magnetic resonance imaging (fMRI) has revealed altered activation among recent and abstinent adult users. Here, we compared fMRI response during a spatial working memory (SWM) task between adolescent marijuana users with brief and sustained durations of abstinence. Participants were 13 recent users (2 – 7 days abstinent), 13 abstinent users (27 – 60 days abstinent), and 18 non-using controls, all ages 15 – 18. Groups were similar on demographics, had no psychiatric or medical disorders, and user groups were similar on substance histories. Teens performed a 2-back SWM task during fMRI. Groups performed similarly on the task, but recent users showed greater fMRI response in medial and left superior prefrontal cortices, as well as bilateral insula. Abstinent users had increased response in the right precentral gyrus (clusters ≥1328 μl, p<.05). This cross-sectional study did not examine changes in brain response among the same participants over time. Yet results suggests that adolescents who recently used marijuana show increased brain activity in regions associated with working memory updating and inhibition, compared to users with weeks to months of abstinence. This study preliminarily suggests that (1) recent marijuana use may disrupt neural connections associated with SWM and result in compensatory brain response, and (2) sustained abstinence from marijuana may be associated with improvements in SWM response among adolescents. PMID:21053763
Deconvolution analyses with tent functions reveal delayed and long-sustained increases of BOLD signals with acupuncture stimulation.
Murase, Tomokazu; Umeda, Masahiro; Fukunaga, Masaki; Tanaka, Chuzo; Higuchi, Toshihiro
We used deconvolution analysis to examine temporal changes in brain activity after acupuncture stimulation and assess brain responses without expected reference functions. We also examined temporal changes in brain activity after sham acupuncture (noninsertive) and scrubbing stimulation. We divided 26 healthy right-handed adults into a group of 13 who received real acupuncture with manual manipulation and a group of 13 who received both tactical stimulations. Functional magnetic resonance imaging (fMRI) sequences consisted of four 15-s stimulation blocks (ON) interspersed between one 30-s and four 45-s rest blocks (OFF) for a total scanning time of 270 s. We analyzed data by using Statistical Parametric Mapping 8 (SPM8), MarsBaR, and Analysis of Functional NeuroImages (AFNI) software. For statistical analysis, we used 3dDeconvolve, part of the AFNI package, to extract the impulse response functions (IRFs) of the fMRI signals on a voxel-wise basis, and we tested the time courses of the extracted IRFs for the stimulations. We found stimulus-specific impulse responses of blood oxygen level-dependent (BOLD) signals in various brain regions. We observed significantly delayed and long-sustained increases of BOLD signals in several brain regions following real acupuncture compared to sham acupuncture and palm scrubbing, which we attribute to peripheral nocireceptors, flare responses, and processing of the central nervous system. Acupuncture stimulation induced continued activity that was stronger than activity after the other stimulations. We used tent function deconvolution to process fMRI data for acupuncture stimulation and found delayed increasing and delayed decreasing changes in BOLD signal in the somatosensory areas and areas related to pain perception. Deconvolution analyses with tent functions are expected to be useful in extracting complicated and associated brain activity that is delayed and sustained for a long period after various stimulations.
From EEG to BOLD: brain mapping and estimating transfer functions in simultaneous EEG-fMRI acquisitions.
Sato, João R; Rondinoni, Carlo; Sturzbecher, Marcio; de Araujo, Draulio B; Amaro, Edson
Simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) aims to disentangle the description of brain processes by exploiting the advantages of each technique. Most studies in this field focus on exploring the relationships between fMRI signals and the power spectrum at some specific frequency bands (alpha, beta, etc.). On the other hand, brain mapping of EEG signals (e.g., interictal spikes in epileptic patients) usually assumes an haemodynamic response function for a parametric analysis applying the GLM, as a rough approximation. The integration of the information provided by the high spatial resolution of MR images and the high temporal resolution of EEG may be improved by referencing them by transfer functions, which allows the identification of neural driven areas without strong assumptions about haemodynamic response shapes or brain haemodynamic's homogeneity. The difference on sampling rate is the first obstacle for a full integration of EEG and fMRI information. Moreover, a parametric specification of a function representing the commonalities of both signals is not established. In this study, we introduce a new data-driven method for estimating the transfer function from EEG signal to fMRI signal at EEG sampling rate. This approach avoids EEG subsampling to fMRI time resolution and naturally provides a test for EEG predictive power over BOLD signal fluctuations, in a well-established statistical framework. We illustrate this concept in resting state (eyes closed) and visual simultaneous fMRI-EEG experiments. The results point out that it is possible to predict the BOLD fluctuations in occipital cortex by using EEG measurements.
Semantic processing and response inhibition.
Chiang, Hsueh-Sheng; Motes, Michael A; Mudar, Raksha A; Rao, Neena K; Mansinghani, Sethesh; Brier, Matthew R; Maguire, Mandy J; Kraut, Michael A; Hart, John
The present study examined functional MRI (fMRI) BOLD signal changes in response to object categorization during response selection and inhibition. Young adults (N=16) completed a Go/NoGo task with varying object categorization requirements while fMRI data were recorded. Response inhibition elicited increased signal change in various brain regions, including medial frontal areas, compared with response selection. BOLD signal in an area within the right angular gyrus was increased when higher-order categorization was mandated. In addition, signal change during response inhibition varied with categorization requirements in the left inferior temporal gyrus (lIT). lIT-mediated response inhibition when inhibiting the response only required lower-order categorization, but lIT mediated both response selection and inhibition when selecting and inhibiting the response required higher-order categorization. The findings characterized mechanisms mediating response inhibition associated with semantic object categorization in the 'what' visual object memory system.
Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.
Lundengård, Karin; Cedersund, Gunnar; Sten, Sebastian; Leong, Felix; Smedberg, Alexander; Elinder, Fredrik; Engström, Maria
Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data
Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI
Lundengård, Karin; Cedersund, Gunnar; Sten, Sebastian; Leong, Felix; Smedberg, Alexander; Elinder, Fredrik
Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data
Nicotine effects on brain function during a visual oddball task: a comparison between conventional and EEG-informed fMRI analysis.
Warbrick, Tracy; Mobascher, Arian; Brinkmeyer, Jürgen; Musso, Francesco; Stoecker, Tony; Shah, N Jon; Fink, Gereon R; Winterer, Georg
In a previous oddball task study, it was shown that the inclusion of electrophysiology (EEG), that is, single-trial P3 ERP parameters, in the analysis of fMRI responses can detect activation that is not apparent with conventional fMRI data modeling strategies [Warbrick, T., Mobascher, A., Brinkmeyer, J., Musso, F., Richter, N., Stoecker, T., et al. Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task. Neuroimage, 47, 1532-1544, 2009]. Given that P3 is modulated by nicotine, including P3 parameters in the fMRI analysis might provide additional information about nicotine effects on brain function. A 1-mg nasal nicotine spray (0.5 mg each nostril) or placebo (pepper) spray was administered in a double-blind, placebo-controlled, within-subject, randomized, cross-over design. Simultaneous EEG-fMRI and behavioral data were recorded from 19 current smokers in response to an oddball-type visual choice RT task. Conventional general linear model analysis and single-trial P3 amplitude informed general linear model analysis of the fMRI data were performed. Comparing the nicotine with the placebo condition, reduced RTs in the nicotine condition were related to decreased BOLD responses in the conventional analysis encompassing the superior parietal lobule, the precuneus, and the lateral occipital cortex. On the other hand, reduced RTs were related to increased BOLD responses in the precentral and postcentral gyri, and ACC in the EEG-informed fMRI analysis. Our results show how integrated analyses of simultaneous EEG-fMRI data can be used to detect nicotine effects that would not have been revealed through conventional analysis of either measure in isolation. This emphasizes the significance of applying multimodal imaging methods to pharmacoimaging.
Physiological characterization of a robust survival rodent fMRI method.
Brynildsen, Julia K; Hsu, Li-Ming; Ross, Thomas J; Stein, Elliot A; Yang, Yihong; Lu, Hanbing
Anesthetics are commonly used in preclinical functional MRI studies. It is well-appreciated that proper choice of anesthetics is of critical importance for maintaining a physiologically normal range of autonomic functioning. A recent study, using a low dose of dexmedetomidine (active isomer of medetomidine) in combination with a low dose of isoflurane, suggested stable measurements across repeated fMRI experiments in individual animals with each session lasting up to several hours. The rat default mode network has been successfully identified using this preparation, indicating that this protocol minimally disturbs brain network functions. However, medetomidine is known to cause peripheral vasoconstriction, respiratory suppression, and bradycardia, each of which could independently confound the BOLD signal. The goal of this study was to systematically characterize physiological conditions for fMRI experiments under this anesthetic regimen. To this end, we acquired somatosensory stimulation "task-evoked" and resting-state fMRI to evaluate the integrity of neurovascular coupling and brain network function during three time windows (0-30min, 30-90min, and 90-150min) following dexmedetomidine initiation. Results demonstrate that both evoked BOLD response and resting-state fMRI signal remained stable during the 90-150min time window, while autonomic physiological parameters maintained near-normal conditions during this period. Our data suggest that using a spontaneously-inhaled, low dose of isoflurane in combination with a continuous low dose of dexmedetomidine is a viable option for longitudinal imaging studies in rats.
Silent and continuous fMRI scanning differentially modulate activation in an auditory language comprehension task.
Schmidt, Conny F; Zaehle, Tino; Meyer, Martin; Geiser, Eveline; Boesiger, Peter; Jancke, Lutz
Sparse temporal acquisition schemes have been adopted to investigate the neural correlates of human audition using blood-oxygen-level dependent (BOLD) based functional magnetic resonance imaging (fMRI) devoid of ambient confounding acoustic scanner noise. These schemes have previously been extended to clustered-sparse temporal acquisition designs which record several subsequent BOLD contrast images in rapid succession in order to enhance temporal sampling efficiency. In the present study we demonstrate that an event-related task design can effectively be combined with a clustered temporal acquisition technique in an auditory language comprehension task. The same fifteen volunteers performed two separate auditory runs which either applied customary fMRI acquisition (CA) composed of continuous scanner noise or "silent" fMRI built on a clustered temporal acquisition (CTA) protocol. In accord with our hypothesis, the CTA scheme relative to the CA protocol is accompanied by significantly stronger functional responses along the entire superior temporal plane. By contrast, the bilateral insulae engage more strongly during continuous scanning. A post-hoc region-of-interest analysis reveals cortical activation in subportions of the supratemporal plane which varies as a function of acquisition protocol. The middle part of the supratemporal plane shows a rightward asymmetry only for the CTA scheme while the posterior supratemporal plane exposes a significantly stronger leftward asymmetry during the CTA. Our findings implicate that silent fMRI is advantageous when it comes to the exploration of auditory and speech functions residing in the supratemporal plane.
Cortical sensory map rearrangement after spinal cord injury: fMRI responses linked to Nogo signalling.
Endo, Toshiki; Spenger, Christian; Tominaga, Teiji; Brené, Stefan; Olson, Lars
Cortical sensory maps can reorganize in the adult brain in an experience-dependent manner. We monitored somatosensory cortical reorganization after sensory deafferentation using functional magnetic resonance imaging (fMRI) in rats subjected to complete transection of the mid-thoracic spinal cord. Cortical representation in response to spared forelimb stimulation was observed to enlarge and invade adjacent sensory-deprived hind limb territory in the primary somatosensory cortex as early as 3 days after injury. Functional MRI also demonstrated long-term cortical plasticity accompanied by increased thalamic activation. To support the notion that alterations of cortical neuronal circuitry after spinal cord injury may underlie the fMRI changes, we quantified transcriptional activities of several genes related to cortical plasticity including the Nogo receptor (NgR), its co-receptor LINGO-1 and brain derived neurotrophic factor (BDNF), using in situ hybridization. We demonstrate that NgR and LINGO-1 are down-regulated specifically in cortical areas deprived of sensory input and in adjacent cortex from 1 day after injury, while BDNF is up-regulated. Our results demonstrate that cortical neurons react to sensory deprivation by decreasing transcriptional activities of genes encoding the Nogo receptor components in the sensory deprived and the anatomically adjacent non-deprived area. Combined with the BDNF up-regulation, these changes presumably allow structural changes in the neuropil. Our observations therefore suggest an involvement of Nogo signalling in cortical activity-dependent plasticity in the somatosensory system. In spinal cord injury, cortical reorganization as shown here can become a disadvantage, much like the situation in amblyopia or phantom sensation. Successful strategies to repair sensory pathways at the spinal cord level may not lead to proper reestablishment of cortical connections, once deprived hind limb cortical areas have been reallocated to forelimb
Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe
Sakadžić, Sava; Lesage, Frédéric; Musacchia, Joseph J.; Lefebvre, Joël; Fang, Qianqian; Yücel, Meryem A.; Evans, Karleyton C.; Mandeville, Emiri T.; Cohen-Adad, Jülien; Polimeni, Jon̈athan R.; Yaseen, Mohammad A.; Lo, Eng H.; Greve, Douglas N.; Buxton, Richard B.; Dale, Anders M.; Devor, Anna; Boas, David A.
The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences. PMID:25716864
Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe.
Gagnon, Louis; Sakadžić, Sava; Lesage, Frédéric; Musacchia, Joseph J; Lefebvre, Joël; Fang, Qianqian; Yücel, Meryem A; Evans, Karleyton C; Mandeville, Emiri T; Cohen-Adad, Jülien; Polimeni, Jonathan R; Yaseen, Mohammad A; Lo, Eng H; Greve, Douglas N; Buxton, Richard B; Dale, Anders M; Devor, Anna; Boas, David A
The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.
Precise spatial co-registration in simultaneous fNIRS and fMRI measurements using markers coaxially fixable to the optodes
NASA Astrophysics Data System (ADS)
Yamada, Toru; Matsuda, Keiji; Iwano, Takayuki; Umeyama, Shinji
Similar to blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), functional nearinfrared spectroscopy (fNIRS) observes regional hemodynamic responses associated with neuronal activation. However, the conventional criteria for detecting true positive fNIRS and fMRI signals appear to be based on different understandings of cerebral hemodynamics. Considerable numbers of fNIRS studies have ascribed the increase in oxygenated hemoglobin to a typical sign of functional activation, whereas the corresponding BOLD signal in fMRI directly correlates with a decrease in deoxygenated hemoglobin. This inconsistency requires solution through the simultaneous measurements of fNIRS and fMRI. In practice, however, there remain several technical problems associated with conducting simultaneous measurements with high reproducibility. One issue is the precise spatial registration of NIRS optodes in MR images. We prepared marker containers of an annular shape that can be coaxially fixed to the optode. Liquid paraffin with α-tocopheryl acetate, which exhibits a bright contrast in T1-weighted MR images of human heads, was solidified in each container by adding higher fatty acid. A subject wearing the marker-fixed optodes at parietal area participated in preliminary fNIRS and fMRI experiments; the subject was instructed to execute single-sided hand finger tapping. The positions showed that deoxygenated hemoglobin decreases in fNIRS coincided with the BOLD-positive region in fMRI. The prepared marker is chemically stable and repetitively usable. We believe that this simple method contributes precision to the co-registration of fNIRS and fMRI.
Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI.
Cao, Jianbo; An, Hengqing; Huang, Xinglu; Fu, Guifeng; Zhuang, Rongqiang; Zhu, Lei; Xie, Jin; Zhang, Fan
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis
Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI
NASA Astrophysics Data System (ADS)
Cao, Jianbo; An, Hengqing; Huang, Xinglu; Fu, Guifeng; Zhuang, Rongqiang; Zhu, Lei; Xie, Jin; Zhang, Fan
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis
Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia.
Fryer, Susanna L; Roach, Brian J; Ford, Judith M; Turner, Jessica A; van Erp, Theo G M; Voyvodic, James; Preda, Adrian; Belger, Aysenil; Bustillo, Juan; O'Leary, Daniel; Mueller, Bryon A; Lim, Kelvin O; McEwen, Sarah C; Calhoun, Vince D; Diaz, Michelle; Glover, Gary; Greve, Douglas; Wible, Cynthia G; Vaidya, Jatin; Potkin, Steven G; Mathalon, Daniel H
The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to
Impulsivity and aggression mediate regional brain responses in Borderline Personality Disorder: An fMRI study.
Soloff, Paul H; Abraham, Kristy; Burgess, Ashley; Ramaseshan, Karthik; Chowdury, Asadur; Diwadkar, Vaibhav A
Fronto-limbic brain networks involved in regulation of impulsivity and aggression are abnormal in Borderline Personality Disorder (BPD). However, it is unclear whether, or to what extent, these personality traits actually modulate brain responses during cognitive processing. Using fMRI, we examined the effects of trait impulsivity, aggression, and depressed mood on regional brain responses in 31 female BPD and 25 control subjects during a Go No-Go task using Ekman faces as targets. First-level contrasts modeled effects of negative emotional context. Second-level regression models used trait impulsivity, aggression and depressed mood as predictor variables of regional brain activations. In BPD, trait impulsivity was positively correlated with activation in the dorsal anterior cingulate cortex, orbital frontal cortex (OFC), basal ganglia (BG), and dorsolateral prefrontal cortex, with no areas of negative correlation. In contrast, aggression was negatively correlated with activation in OFC, hippocampus, and BG, with no areas of positive correlation. Depressed mood had a generally dampening effect on activations. Effects of trait impulsivity on healthy controls differed from effects in BPD, suggesting a disorder-specific response. Negative emotional context and trait impulsivity, but not aggression or depression, diminished task performance across both groups. Negative emotional context may interfere with cognitive functioning in BPD through interaction with the neurobiology of personality traits.
An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders.
Masten, Carrie L; Colich, Natalie L; Rudie, Jeffrey D; Bookheimer, Susan Y; Eisenberger, Naomi I; Dapretto, Mirella
Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.
Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest.
Shmuel, Amir; Leopold, David A
Recent studies have demonstrated large amplitude spontaneous fluctuations in functional-MRI (fMRI) signals in humans in the resting state. Importantly, these spontaneous fluctuations in blood-oxygenation-level-dependent (BOLD) signal are often synchronized over distant parts of the brain, a phenomenon termed functional-connectivity. Functional-connectivity is widely assumed to reflect interregional coherence of fluctuations in activity of the underlying neuronal networks. Despite the large body of human imaging literature on spontaneous activity and functional-connectivity in the resting state, the link to underlying neural activity remains tenuous. Through simultaneous fMRI and intracortical neurophysiological recording, we demonstrate correlation between slow fluctuations in BOLD signals and concurrent fluctuations in the underlying locally measured neuronal activity. This correlation varied with time-lag of BOLD relative to neuronal activity, resembling a traditional hemodynamic response function with peaks at approximately 6 s lag of BOLD signal. The correlations were reliably detected when the neuronal signal consisted of either the spiking rate of a small group of neurons, or relative power changes in the multi-unit activity band, and particularly in the local field potential gamma band. Analysis of correlation between the voxel-by-voxel fMRI time-series and the neuronal activity measured within one cortical site showed patterns of correlation that slowly traversed cortex. BOLD fluctuations in widespread areas in visual cortex of both hemispheres were significantly correlated with neuronal activity from a single recording site in V1. To the extent that our V1 findings can be generalized to other cortical areas, fMRI-based functional-connectivity between remote regions in the resting state can be linked to synchronization of slow fluctuations in the underlying neuronal signals.
The spatiospectral characterization of brain networks: fusing concurrent EEG spectra and fMRI maps.
Bridwell, David A; Wu, Lei; Eichele, Tom; Calhoun, Vince D
Different imaging modalities capture different aspects of brain activity. Functional magnetic resonance imaging (fMRI) reveals intrinsic networks whose BOLD signals have periods from 100 s (0.01 Hz) to about 10s (0.1 Hz). Electroencephalographic (EEG) recordings, in contrast, commonly reflect cortical electrical fluctuations with periods up to 20 ms (50 Hz) or above. We examined the correspondence between intrinsic fMRI and EEG network activity at rest in order to characterize brain networks both spatially (with fMRI) and spectrally (with EEG). Brain networks were separately identified within the concurrently recorded fMRI and EEG at the aggregate group level with group independent component analysis and the association between spatial fMRI and frequency by spatial EEG sources was examined by deconvolving their component time courses. The two modalities are considered linked if the estimated impulse response function (IRF) is significantly non-zero at biologically plausible delays. We found that negative associations were primarily present within two of five alpha components, which highlights the importance of considering multiple alpha sources in EEG-fMRI. Positive associations were primarily present within the lower (e.g. delta and theta) and higher (e.g. upper beta and lower gamma) spectral regions, sometimes within the same fMRI components. Collectively, the results demonstrate a promising approach to characterize brain networks spatially and spectrally, and reveal that positive and negative associations appear within partially distinct regions of the EEG spectrum.
The power of using functional fMRI on small rodents to study brain pharmacology and disease
Jonckers, Elisabeth; Shah, Disha; Hamaide, Julie; Verhoye, Marleen; Van der Linden, Annemie
Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal's physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological
Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study
Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J.; Davey, Christopher G.; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M.; Fernández-Aranda, Fernando; Cardoner, Narcís
Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN. PMID:26197051
[fMRI study of deliberate deception].
Kireev, M V; Korotkov, A D; Medvedev, C V
The aim of the present research was to study the deliberate deception. Event related functional magnetic resonance (fMRI) imaging technique was used to assess the changes in functional brain activity by virtue of recording blood oxygen level dependant signal (BOLD-signal). 12 right-handed healthy volunteers aged 19-44 participated in the study. BOLD images were acquired in three different experimental trials. There were deliberate deception, manipulative honest and control truthful trials (catch trials). The main finding of the present study is that the deliberate deception and manipulative honest actions in comparison with instructed truthful responding was characterized by BOLD signal increase within the anterior cingulated cortex (ACC), frontal and parietal areas as well. Comparison of present fMRI data with results demonstrated in our previous research implemented with event related potentials technique points to the involvement of the brain mechanism of error detection to brain processing of deliberate deception.
ERIC Educational Resources Information Center
Gallo, Don
"Bold Books for Teenagers" provides dynamic, informative viewpoints on important issues in publishing and teaching contemporary literature, especially literature for adolescents. Reviews of young adult literature also appear in this column. This article examines how English teachers can help students explore their interests without promoting any…
A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data.
Wu, Guo-Rong; Liao, Wei; Stramaglia, Sebastiano; Ding, Ju-Rong; Chen, Huafu; Marinazzo, Daniele
A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. In a recent study it has been proposed that relevant information in resting-state fMRI can be obtained by inspecting the discrete events resulting in relatively large amplitude BOLD signal peaks. Following this idea, we consider resting fMRI as 'spontaneous event-related', we individuate point processes corresponding to signal fluctuations with a given signature, extract a region-specific HRF and use it in deconvolution, after following an alignment procedure. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the
The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories.
Carhart-Harris, R L; Wall, M B; Erritzoe, D; Kaelen, M; Ferguson, B; De Meer, I; Tanner, M; Bloomfield, M; Williams, T M; Bolstridge, M; Stewart, L; Morgan, C J; Newbould, R D; Feilding, A; Curran, H V; Nutt, D J
3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.
Vowel-specific mismatch responses in the anterior superior temporal gyrus: an fMRI study.
Leff, Alexander P; Iverson, Paul; Schofield, Thomas M; Kilner, James M; Crinion, Jennifer T; Friston, Karl J; Price, Cathy J
There have been many functional imaging studies that have investigated the neural correlates of speech perception by contrasting neural responses to speech and "speech-like" but unintelligible control stimuli. A potential drawback of this approach is that intelligibility is necessarily conflated with a change in the acoustic parameters of the stimuli. The approach we have adopted is to take advantage of the mismatch response elicited by an oddball paradigm to probe neural responses in temporal lobe structures to a parametrically varied set of deviants in order to identify brain regions involved in vowel processing. Thirteen normal subjects were scanned using a functional magnetic resonance imaging (fMRI) paradigm while they listened to continuous trains of auditory stimuli. Three classes of stimuli were used: 'vowel deviants' and two classes of control stimuli: one acoustically similar ('single formants') and the other distant (tones). The acoustic differences between the standard and deviants in both the vowel and single-formant classes were designed to match each other closely. The results revealed an effect of vowel deviance in the left anterior superior temporal gyrus (aSTG). This was most significant when comparing all vowel deviants to standards, irrespective of their psychoacoustic or physical deviance. We also identified a correlation between perceptual discrimination and deviant-related activity in the dominant superior temporal sulcus (STS), although this effect was not stimulus specific. The responses to vowel deviants were in brain regions implicated in the processing of intelligible or meaningful speech, part of the so-called auditory "what" processing stream. Neural components of this pathway would be expected to respond to sudden, perhaps unexpected changes in speech signal that result in a change to narrative meaning.
Counterfactual thinking and reward processing: an fMRI study of responses to gamble outcomes.
Henderson, Sarah E; Norris, Catherine J
The process of comparing obtained outcomes to alternative possible outcomes, known as counterfactual thinking, is inescapable in daily life; however, the neurocognitive mechanisms underlying counterfactual thinking and how they influence emotional responses to better and worse outcomes is not well understood. We conducted an event-related functional magnetic resonance imaging (fMRI) gambling study in which participants were informed of two equally possible outcomes of a card gamble before they selected a card. Participants reported experiencing mixed emotions (i.e., both positive and negative affect) for disappointing wins (winning the lesser of two amounts) and relieving losses (losing the lesser of two amounts). Neuroimaging results supported the hypothesis that these mixed emotions were associated with activation of a fronto-parietal network, which subsequently influenced processing in reward and punishment regions (dorsal and ventral striatum, right anterior insula). The fronto-parietal network was sensitive to outcomes that resulted in mixed emotions, whereas reward and punishment regions were sensitive to comparisons between obtained and unobtained outcomes. These findings provide insight into the neurocognitive mechanisms underlying the mixed emotional experiences that result from counterfactual comparisons, and inform our understanding of how the brain is optimized to use the wealth of environmental information to inform current and future behavior.
Contextual effects on cognitive control and BOLD activation in single versus mixed saccade tasks.
Pierce, Jordan E; McDowell, Jennifer E
The context or trial history of a task influences response efficiency in mixed paradigms based on cognitive control demands for task set selection. In the current study, the impact of context on prosaccade and antisaccade trials in single and mixed tasks was investigated with BOLD fMRI. Prosaccades require a look towards a newly appearing target, while antisaccades require cognitive control for prepotent response inhibition and generation of a saccade to the opposite location. Results indicated slower prosaccade reaction times and more antisaccade errors for switched than repeated or single trials, and slower antisaccade reaction times for single than mixed trials. BOLD activation was greater for the mixed than the single context in frontal eye fields and precuneus, while switch trials had greater activation than repeat trials in posterior parietal and middle occipital cortex. Greater antisaccade activation was observed overall in saccade circuitry, although effects were evident primarily for the mixed task when considered separately. Finally, an interaction was observed in superior frontal cortex, precuneus, anterior cingulate, and thalamus with strong responses for antisaccade switch trials in the latter two regions. Altogether this response pattern demonstrated the sensitivity of cognitive control to changing task conditions, especially due to task switching costs. Such context-specific differences highlight the importance of trial history when assessing cognitive control.
EEG and FMRI coregistration to investigate the cortical oscillatory activities during finger movement.
Formaggio, Emanuela; Storti, Silvia Francesca; Avesani, Mirko; Cerini, Roberto; Milanese, Franco; Gasparini, Anna; Acler, Michele; Pozzi Mucelli, Roberto; Fiaschi, Antonio; Manganotti, Paolo
Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.
Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats
Ferris, Craig F.; Yee, Jason R.; Kenkel, William M.; Dumais, Kelly Marie; Moore, Kelsey; Veenema, Alexa H.; Kulkarni, Praveen; Perkybile, Allison M.; Carter, C. Sue
A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood–brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose–response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity. PMID:26441574
A new approach to measure single-event related brain activity using real-time fMRI: feasibility of sensory, motor, and higher cognitive tasks.
Posse, S; Binkofski, F; Schneider, F; Gembris, D; Frings, W; Habel, U; Salloum, J B; Mathiak, K; Wiese, S; Kiselev, V; Graf, T; Elghahwagi, B; Grosse-Ruyken, M L; Eickermann, T
Real-time fMRI is a rapidly emerging methodology that enables monitoring changes in brain activity during an ongoing experiment. In this article we demonstrate the feasibility of performing single-event sensory, motor, and higher cognitive tasks in real-time on a clinical whole-body scanner. This approach requires sensitivity optimized fMRI methods: Using statistical parametric mapping we quantified the spatial extent of BOLD contrast signal changes as a function of voxel size and demonstrate that sacrificing spatial resolution and readout bandwidth improves the detection of signal changes in real time. Further increases in BOLD contrast sensitivity were obtained by using real-time multi-echo EPI. Real-time image analysis was performed using our previously described Functional Imaging in REal time (FIRE) software package, which features real-time motion compensation, sliding window correlation analysis, and automatic reference vector optimization. This new fMRI methodology was validated using single-block design paradigms of standard visual, motor, and auditory tasks. Further, we demonstrate the sensitivity of this method for online detection of higher cognitive functions during a language task using single-block design paradigms. Finally, we used single-event fMRI to characterize the variability of the hemodynamic impulse response in primary and supplementary motor cortex in consecutive trials using single movements. Real-time fMRI can improve reliability of clinical and research studies and offers new opportunities for studying higher cognitive functions.
Baseline blood oxygenation modulates response amplitude
Lu, Hanzhang; Zhao, Chenguang; Ge, Yulin; Lewis-Amezcua, Kelly
Although BOLD fMRI provides a useful tool for probing neuronal activities, large inter-subject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task-evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T2-Relaxation-Under-Spin-Tagging MRI, yielding baseline oxygenation of 63.7±7.2% in sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal and vice versa. For every 10% difference in baseline oxygenation across subjects, the BOLD and cerebral blood flow signal differ by -0.4% and -30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject. PMID:18666103
Altered Dynamics of the fMRI Response to Faces in Individuals with Autism
Kleinhans, Natalia M.; Richards, Todd; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth
Abnormal fMRI habituation in autism spectrum disorders (ASD) has been proposed as a critical component in social impairment. This study investigated habituation to fearful faces and houses in ASD and whether fMRI measures of brain activity discriminate between ASD and typically developing (TD) controls. Two identical fMRI runs presenting masked fearful faces, houses, and scrambled images were collected. We found significantly reduced habituation to fearful faces but not houses in ASD. In addition, amygdala habituation to faces had robust discriminability (ASD versus TD; area under the curve (AUC) = .852, p<.000). In contrast, habituation to houses had no predictive value (AUC = .573, p =.365). Amygdala habituation to emotional faces may be useful for quantifying risk in ASD. PMID:26340957
Brain regions responsible for tinnitus distress and loudness: a resting-state FMRI study.
Ueyama, Takashi; Donishi, Tomohiro; Ukai, Satoshi; Ikeda, Yorihiko; Hotomi, Muneki; Yamanaka, Noboru; Shinosaki, Kazuhiro; Terada, Masaki; Kaneoke, Yoshiki
Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.
The BOLD Response during Stroop Task-Like Inhibition Paradigms: Effects of Task Difficulty and Task-Relevant Modality
ERIC Educational Resources Information Center
Mitchell, Rachel L. C.
Previous studies of the Stroop task propose two key mediators: the prefrontal and cingulate cortices but hints exist of functional specialization within these regions. This study aimed to examine the effect of task modality upon the prefrontal and cingulate response by examining the response to colour, number, and shape Stroop tasks whilst BOLD…
The NIH experience in first advancing fMRI.
Turner, Robert
The introduction of functional MRI at NIH in 1992 was the outcome of research goals first formulated by Turner in 1983. Between 1988 and 1990, Turner worked at NIH on actively-shielded gradient coils and the implementation of EPI-based techniques, especially diffusion-weighted EPI. His work on hypoxia in cat brain in 1990 directly inspired Ken Kwong's demonstration of BOLD contrast in humans at MGH in May 1991. Turner collaborated actively with this MGH team, the first group to map entirely noninvasively human brain activity due to visual stimulation. He introduced BOLD fMRI at NIH in February 1992. This paper reviews the steps that led up to BOLD EPI, and Turner's initial applications of BOLD fMRI at NIH.
Are Errors Differentiable from Deceptive Responses when Feigning Memory Impairment? An fMRI Study
ERIC Educational Resources Information Center
Lee, Tatia M. C.; Au, Ricky K. C.; Liu, Ho-Ling; Ting, K. H.; Huang, Chih-Mao; Chan, Chetwyn C. H.
Previous neuroimaging studies have suggested that the neural activity associated with truthful recall, with false memory, and with feigned memory impairment are different from one another. Here, we report a functional magnetic resonance imaging (fMRI) study that addressed an important but yet unanswered question: Is the neural activity associated…
Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque
Kaneko, Takaaki; Saleem, Kadharbatcha S.; Berman, Rebecca A.; Leopold, David A.
Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. SIGNIFICANCE STATEMENT Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This "reafferent" motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self
Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects
van Opstal, Anna M.; Westerink, Anna M.; Teeuwisse, Wouter M.; van der Geest, Mirjam A. M.; van Furth, Eric F.; van der Grond, Jeroen
Background: Inconsistent findings about the neurobiology of Anorexia Nervosa (AN) hinder the development of effective treatments for this severe mental disorder. Therefore, the need arises for elucidation of neurobiological factors involved in the pathophysiology of AN. The hypothalamus plays a key role in the neurobiological processes that govern food intake and energy homeostasis, processes that are disturbed in anorexia nervosa (AN). The present study will assess the hypothalamic response to energy intake and the hypothalamic structure in patients with AN and healthy controls. Methods: Ten women aged 18–30 years diagnosed with AN and 11 healthy, lean (BMI < 23 kg/m2) women in the same age range were recruited. We used functional magnetic resonance imaging (MRI) to determine function of the hypothalamus in response to glucose. Structural MRI was used to determine differences in hypothalamic volume and local gray matter volume using manual segmentation and voxel-based morphometry. Results: No differences were found in hypothalamic volume and neuronal activity in response to a glucose load between the patients and controls. Whole brain structural analysis showed a significant decrease in gray matter volume in the cingulate cortex in the AN patients, bilaterally. Conclusions: We argue that in spite of various known changes in the hypothalamus the direct hypothalamic response to glucose intake is similar in AN patients and healthy controls. PMID:25999808
Functional MRI and neural responses in a rat model of Alzheimer's disease
Sanganahalli, Basavaraju G.; Herman, Peter; Behar, Kevin L.; Blumenfeld, Hal; Rothman, Douglas L.; Hyder, Fahmeed
Based on the hypothesis that brain plaques and tangles can affect cortical functions in Alzheimer's disease (AD) and thus modify functional activity, we investigated functional responses in an AD rat model (called the Samaritan Alzheimer's rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer's disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer's disease. PMID:23648961
Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women
de Jong, Peter J.; Georgiadis, Janniko R.
Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile–vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899
Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women.
Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R
Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli.
Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study.
Bolstad, Ingeborg; Andreassen, Ole A; Groote, Inge; Server, Andres; Sjaastad, Ivar; Kapur, Shitij; Jensen, Jimmy
The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model - a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans.
The relationship between oscillatory EEG activity and the laminar-specific BOLD signal
Scheeringa, René; Koopmans, Peter J.; van Mourik, Tim; Jensen, Ole; Norris, David G.
Electrophysiological recordings in animals have indicated that visual cortex γ-band oscillatory activity is predominantly observed in superficial cortical layers, whereas α- and β-band activity is stronger in deep layers. These rhythms, as well as the different cortical layers, have also been closely related to feedforward and feedback streams of information. Recently, it has become possible to measure laminar activity in humans with high-resolution functional MRI (fMRI). In this study, we investigated whether these different frequency bands show a differential relation with the laminar-resolved blood-oxygen level-dependent (BOLD) signal by combining data from simultaneously recorded EEG and fMRI from the early visual cortex. Our visual attention paradigm allowed us to investigate how variations in strength over trials and variations in the attention effect over subjects relate to each other in both modalities. We demonstrate that γ-band EEG power correlates positively with the superficial layers' BOLD signal and that β-power is negatively correlated to deep layer BOLD and α-power to both deep and superficial layer BOLD. These results provide a neurophysiological basis for human laminar fMRI and link human EEG and high-resolution fMRI to systems-level neuroscience in animals. PMID:27247416
The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.
Tsurugizawa, T; Uematsu, A; Uneyama, H; Torii, K
The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats.
Intra- and Inter- Subject Variability of High Field fMRI Digit Maps in Somatosensory Area 3b of New World Monkeys
Zhang, Na; Wang, Feng; Turner, Greg H.; Gore, John C.; Avison, Malcolm J.; Chen, Li M.
This study evaluates the intra- and inter- subject variability of digit maps in area 3b of anesthetized squirrel monkeys. Maps were collected using high field Blood Oxygenation Level Dependent (BOLD) fMRI. BOLD responses to individual digit stimulations were mapped and their response properties (location, area of activation, % signal change, time to peak response) were compared within and across imaging sessions separated by up to 20 months. During single digit stimulation using a block design, the spatio-temporal response of the BOLD signal for individual runs within and across sessions and animals was well conserved, with a time to peak BOLD response of 20 ± 4 sec. The variability in the center of BOLD activation in area 3b was 0.41 ± 0.24 mm (mean ± SD) across individual 5–7 minutes runs within a scanning session and 0.55 ± 0.15 mm across sessions. The average signal change across all animals, runs and sessions was 0.62 ± 0.38 %, and varied 32% within and 40% across sessions. In a comparison of the stability and reproducibility of the area of single digit activation obtained using three approaches, use of a fixed statistical threshold (p<10−5) yielded an average area of 4.8 ± 3.5 mm2 (mean ± SD), adaptive statistical thresholding 1.32 ± 1.259 mm2 (mean ± SD), and combined fixed statistical and adaptive BOLD signal amplitude 4.4 ± 2.5 mm2 (mean ± SD) across image runs and sessions. The somatotopic organization was stable within animals across sessions, while across animals, there was some variation in overall activation pattern and inter-digit distances. These results confirm that BOLD activation maps of single digits in area 3b as characterized by activation center, signal amplitudes, and temporal profile are very stable. The activation sizes determined by various criteria are the most variable measure in this preparation, but adaptive statistical thresholding appears to yield the most stable and reproducible maps. This study serves as a baseline
Mapping and correction of vascular hemodynamic latency in the BOLD signal.
Chang, Catie; Thomason, Moriah E; Glover, Gary H
Correlation and causality metrics can be applied to blood-oxygen level-dependent (BOLD) signal time series in order to infer neural synchrony and directions of information flow from fMRI data. However, the BOLD signal reflects both the underlying neural activity and the vascular response, the latter of which is governed by local vasomotor physiology. The presence of potential vascular latency differences thus poses a confound in the detection of neural synchrony as well as inferences about the causality of neural processes. In the present study, we investigate the use of a breath holding (BH) task for characterizing and correcting for voxel-wise neurovascular latency differences across the whole brain. We demonstrate that BH yields reliable measurements of relative timing differences between voxels, and further show that a BH-derived latency correction can impact both functional connectivity maps of the resting-state default-mode network and activation maps of an event-related working memory (WM) task.
fMRI activation patterns in an analytic reasoning task: consistency with EEG source localization
NASA Astrophysics Data System (ADS)
Li, Bian; Vasanta, Kalyana C.; O'Boyle, Michael; Baker, Mary C.; Nutter, Brian; Mitra, Sunanda
Functional magnetic resonance imaging (fMRI) is used to model brain activation patterns associated with various perceptual and cognitive processes as reflected by the hemodynamic (BOLD) response. While many sensory and motor tasks are associated with relatively simple activation patterns in localized regions, higher-order cognitive tasks may produce activity in many different brain areas involving complex neural circuitry. We applied a recently proposed probabilistic independent component analysis technique (PICA) to determine the true dimensionality of the fMRI data and used EEG localization to identify the common activated patterns (mapped as Brodmann areas) associated with a complex cognitive task like analytic reasoning. Our preliminary study suggests that a hybrid GLM/PICA analysis may reveal additional regions of activation (beyond simple GLM) that are consistent with electroencephalography (EEG) source localization patterns.
Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues.
McClernon, Francis J; Kozink, Rachel V; Rose, Jed E
Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerström test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.
Spontaneous EEG alpha oscillation interacts with positive and negative BOLD responses in the visual-auditory cortices and default-mode network.
Mayhew, Stephen D; Ostwald, Dirk; Porcaro, Camillo; Bagshaw, Andrew P
The human brain is continually, dynamically active and spontaneous fluctuations in this activity play a functional role in affecting both behavioural and neuronal responses. However, the mechanisms through which this occurs remain poorly understood. Simultaneous EEG-fMRI is a promising technique to study how spontaneous activity modulates the brain's response to stimulation, as temporal indices of ongoing cortical excitability can be integrated with spatially localised evoked responses. Here we demonstrate an interaction between the ongoing power of the electrophysiological alpha oscillation and the magnitude of both positive (PBR) and negative (NBR) fMRI responses to two contrasts of visual checkerboard reversal. Furthermore, the amplitude of pre-stimulus EEG alpha-power significantly modulated the amplitude and shape of subsequent PBR and NBR to the visual stimulus. A nonlinear reduction of visual PBR and an enhancement of auditory NBR and default-mode network NBR were observed in trials preceded by high alpha-power. These modulated areas formed a functionally connected network during a separate resting-state recording. Our findings suggest that the "baseline" state of the brain exhibits considerable trial-to-trial variability which arises from fluctuations in the balance of cortical inhibition/excitation that are represented by respective increases/decreases in the power of the EEG alpha oscillation. The consequence of this spontaneous electrophysiological variability is modulated amplitudes of both PBR and NBR to stimulation. Fluctuations in alpha-power may subserve a functional relationship in the visual-auditory network, acting as mediator for both short and long-range cortical inhibition, the strength of which is represented in part by NBR.
Integration of EEG source imaging and fMRI during continuous viewing of natural movies.
Whittingstall, Kevin; Bartels, Andreas; Singh, Vanessa; Kwon, Soyoung; Logothetis, Nikos K
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an
Risk assessment of aggressive behavior in Chinese patients with schizophrenia by fMRI and COMT gene
Tang, Xiaoli; Jin, Jun; Tang, Yi; Cao, Jinbo; Huang, Junjie
Background Blood–oxygen-level dependent functional magnetic resonance imaging (BOLD-fMRI) maps cerebral activity by the hemodynamic response. Catechol-O-methyltransferase (COMT) gene is involved in the metabolism of dopamine. It is reported that both of these can be used to assess the aggression risk in patients with schizophrenia. However, these methods to assess the aggression risk patients with schizophrenia have not been established in China. Therefore, we deliver here a systematic review and meta-analysis based on the studies dealing with Chinese patients. Method Nine fMRI studies and 12 gene studies were included. The data of each study were extracted and summarized. Odds ratios with 95% confidence intervals were estimated on allele, dominant, and recessive models. Publication bias was evaluated by Begg's funnel plot. Results Positive BOLD-fMRI values in the lower central neural system (CNS) and negative values in the high-level CNS were observed in the patients with aggression risk. A strong association was derived from the recessive gene model of COMT polymorphism rs4680 and risk in aggression behavior (odds ratio =2.10). No significant publication bias was identified. Conclusion Aggression behavior in patients with schizophrenia can be indicated by positive BOLD-fMRI values in the lower CNS and negative values in the high-level CNS and by a recessive gene model in COMT polymorphism rs4680. A combined test of fMRI and COMT gene could increase the predictive value. PMID:28223811
Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation
NASA Astrophysics Data System (ADS)
Siegel, Andrew M.; Culver, Joseph P.; Mandeville, Joseph B.; Boas, David A.
The time courses of oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO2] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity.
fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.
Paret, Christian; Ruf, Matthias; Gerchen, Martin Fungisai; Kluetsch, Rosemarie; Demirakca, Traute; Jungkunz, Martin; Bertsch, Katja; Schmahl, Christian; Ende, Gabriele
Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (β=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation.
Neural correlates of experienced moral emotion: an fMRI investigation of emotion in response to prejudice feedback.
Fourie, Melike M; Thomas, Kevin G F; Amodio, David M; Warton, Christopher M R; Meintjes, Ernesta M
Guilt, shame, and embarrassment are quintessential moral emotions with important regulatory functions for the individual and society. Moral emotions are, however, difficult to study with neuroimaging methods because their elicitation is more intricate than that of basic emotions. Here, using functional MRI (fMRI), we employed a novel social prejudice paradigm to examine specific brain regions associated with real-time moral emotion, focusing on guilt and related moral-negative emotions. The paradigm induced intense moral-negative emotion (primarily guilt) in 22 low-prejudice individuals through preprogrammed feedback indicating implicit prejudice against Black and disabled people. fMRI data indicated that this experience of moral-negative emotion was associated with increased activity in anterior paralimbic structures, including the anterior cingulate cortex (ACC) and anterior insula, in addition to areas associated with mentalizing, including the dorsomedial prefrontal cortex, posterior cingulate cortex, and precuneus. Of significance was prominent conflict-related activity in the supragenual ACC, which is consistent with theories proposing an association between acute guilt and behavioral inhibition. Finally, a significant negative association between self-reported guilt and neural activity in the pregenual ACC suggested a role of self-regulatory processes in response to moral-negative affect. These findings are consistent with the multifaceted self-regulatory functions of moral-negative emotions in social behavior.
fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents
Brown, Matthew R. G.; Benoit, James R. A.; Juhás, Michal; Dametto, Ericson; Tse, Tiffanie T.; MacKay, Marnie; Sen, Bhaskar; Carroll, Alan M.; Hodlevskyy, Oleksandr; Silverstone, Peter H.; Dolcos, Florin; Dursun, Serdar M.; Greenshaw, Andrew J.
High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14–17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents. PMID:26483645
Objective Bayesian fMRI analysis—a pilot study in different clinical environments
Magerkurth, Joerg; Mancini, Laura; Penny, William; Flandin, Guillaume; Ashburner, John; Micallef, Caroline; De Vita, Enrico; Daga, Pankaj; White, Mark J.; Buckley, Craig; Yamamoto, Adam K.; Ourselin, Sebastien; Yousry, Tarek; Thornton, John S.; Weiskopf, Nikolaus
Functional MRI (fMRI) used for neurosurgical planning delineates functionally eloquent brain areas by time-series analysis of task-induced BOLD signal changes. Commonly used frequentist statistics protect against false positive results based on a p-value threshold. In surgical planning, false negative results are equally if not more harmful, potentially masking true brain activity leading to erroneous resection of eloquent regions. Bayesian statistics provides an alternative framework, categorizing areas as activated, deactivated, non-activated or with low statistical confidence. This approach has not yet found wide clinical application partly due to the lack of a method to objectively define an effect size threshold. We implemented a Bayesian analysis framework for neurosurgical planning fMRI. It entails an automated effect-size threshold selection method for posterior probability maps accounting for inter-individual BOLD response differences, which was calibrated based on the frequentist results maps thresholded by two clinical experts. We compared Bayesian and frequentist analysis of passive-motor fMRI data from 10 healthy volunteers measured on a pre-operative 3T and an intra-operative 1.5T MRI scanner. As a clinical case study, we tested passive motor task activation in a brain tumor patient at 3T under clinical conditions. With our novel effect size threshold method, the Bayesian analysis revealed regions of all four categories in the 3T data. Activated region foci and extent were consistent with the frequentist analysis results. In the lower signal-to-noise ratio 1.5T intra-operative scanner data, Bayesian analysis provided improved brain-activation detection sensitivity compared with the frequentist analysis, albeit the spatial extents of the activations were smaller than at 3T. Bayesian analysis of fMRI data using operator-independent effect size threshold selection may improve the sensitivity and certainty of information available to guide neurosurgery
Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification.
Kalcher, Klaudius; Boubela, Roland N; Huf, Wolfgang; Našel, Christian; Moser, Ewald
Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments.
Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification
Kalcher, Klaudius; Boubela, Roland N.; Huf, Wolfgang; Našel, Christian; Moser, Ewald
Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments. PMID:26733787
A studyforrest extension, simultaneous fMRI and eye gaze recordings during prolonged natural stimulation
Hanke, Michael; Adelhöfer, Nico; Kottke, Daniel; Iacovella, Vittorio; Sengupta, Ayan; Kaule, Falko R.; Nigbur, Roland; Waite, Alexander Q.; Baumgartner, Florian; Stadler, Jörg
Here we present an update of the studyforrest (http://studyforrest.org) dataset that complements the previously released functional magnetic resonance imaging (fMRI) data for natural language processing with a new two-hour 3 Tesla fMRI acquisition while 15 of the original participants were shown an audio-visual version of the stimulus motion picture. We demonstrate with two validation analyses that these new data support modeling specific properties of the complex natural stimulus, as well as a substantial within-subject BOLD response congruency in brain areas related to the processing of auditory inputs, speech, and narrative when compared to the existing fMRI data for audio-only stimulation. In addition, we provide participants' eye gaze location as recorded simultaneously with fMRI, and an additional sample of 15 control participants whose eye gaze trajectories for the entire movie were recorded in a lab setting—to enable studies on attentional processes and comparative investigations on the potential impact of the stimulation setting on these processes. PMID:27779621
Fixation-related FMRI analysis in the domain of reading research: using self-paced eye movements as markers for hemodynamic brain responses during visual letter string processing.
Richlan, Fabio; Gagl, Benjamin; Hawelka, Stefan; Braun, Mario; Schurz, Matthias; Kronbichler, Martin; Hutzler, Florian
The present study investigated the feasibility of using self-paced eye movements during reading (measured by an eye tracker) as markers for calculating hemodynamic brain responses measured by functional magnetic resonance imaging (fMRI). Specifically, we were interested in whether the fixation-related fMRI analysis approach was sensitive enough to detect activation differences between reading material (words and pseudowords) and nonreading material (line and unfamiliar Hebrew strings). Reliable reading-related activation was identified in left hemisphere superior temporal, middle temporal, and occipito-temporal regions including the visual word form area (VWFA). The results of the present study are encouraging insofar as fixation-related analysis could be used in future fMRI studies to clarify some of the inconsistent findings in the literature regarding the VWFA. Our study is the first step in investigating specific visual word recognition processes during self-paced natural sentence reading via simultaneous eye tracking and fMRI, thus aiming at an ecologically valid measurement of reading processes. We provided the proof of concept and methodological framework for the analysis of fixation-related fMRI activation in the domain of reading research.
Frontal cortex BOLD signal changes in premanifest Huntington disease
Ferraro, Stefania; Piacentini, Sylvie; Mandelli, Maria L.; Bertolino, Nicola; Ghielmetti, Francesco; Epifani, Francesca; Nigri, Anna; Taroni, Franco; Bruzzone, Maria G.; Donato, Stefano Di; Savoiardo, Mario; Mariotti, Caterina; Grisoli, Marina
Objective: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. Methods: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level–dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. Results: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r2 = 0.52). Among the considered striatal volumes, a modest correlation (r2 = 0.29) was observed in the right putamen and p5HD. Conclusion: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD. PMID:24898924
Event-Related Fmri Evidence of Frontotemporal Involvement in Aberrant Response Inhibition and Task Switching in Attention-Deficit/hyperactivity Disorder.
ERIC Educational Resources Information Center
Tamm, Leanne; Menon, Vinod; Ringel, Jessica; Reiss, Allan L.
Objective: Response inhibition deficits are characteristic of individuals with attention-deficit/hyperactivity disorder (ADHD). Previous functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of this dysfunction have used block designs, making it difficult to disentangle activation differences specifically related…
Voluntary Explicit versus Involuntary Conceptual Memory Are Associated with Dissociable fMRI Responses in Hippocampus, Amygdala, and Parietal Cortex for Emotional and Neutral Word Pairs
ERIC Educational Resources Information Center
Ramponi, Cristina; Barnard, Philip J.; Kherif, Ferath; Henson, Richard N.
Although functional neuroimaging studies have supported the distinction between explicit and implicit forms of memory, few have matched explicit and implicit tests closely, and most of these tested perceptual rather than conceptual implicit memory. We compared event-related fMRI responses during an intentional test, in which a group of…
Response inhibition results in the emotional devaluation of faces: neural correlates as revealed by fMRI.
Doallo, Sonia; Raymond, Jane E; Shapiro, Kimron L; Kiss, Monika; Eimer, Martin; Nobre, Anna C
Although it is well established that prior experience with faces determines their subsequent social-emotional evaluation, recent work shows that top-down inhibitory mechanisms, including response inhibition, can lead to social devaluation after even a single, brief exposure. These rapidly induced effects indicate interplay among perceptual, attentional, response-selection and social-emotional networks; yet, the brain mechanisms underlying this are not well understood. This study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanism mediating the relationship between inhibitory control and emotional devaluation. Participants performed two tasks: (i) a Go/No-Go task in response to faces and (ii) a trustworthiness rating task involving the previously seen faces. No-Go faces were rated as significantly less trustworthy than Go faces. By examining brain activations during Task 1, behavioral measures and brain activations obtained in Task 2 could be predicted. Specifically, activity in brain areas during Task 1 associated with (i) executive control and response suppression (i.e. lateral prefrontal cortex) and (ii) affective responses and value representation (i.e. orbitofrontal cortex), systematically covaried with behavioral ratings and amygdala activity obtained during Task 2. The present findings offer insights into the neural mechanisms linking inhibitory processes to affective responses.
Negative urgency and ventromedial prefrontal cortex responses to alcohol cues: fMRI evidence of emotion-based impulsivity
Cyders, Melissa A.; Dzemidzic, Mario; Eiler, William J.; Coskunpinar, Ayca; Karyadi, Kenny; Kareken, David A.
Background Recent research has highlighted the role of emotion-based impulsivity (negative and positive urgency personality traits) for alcohol use and abuse, but has yet to examine how these personality traits interact with the brain's motivational systems. Using functional magnetic resonance imaging (fMRI), we tested if urgency traits and mood induction affected medial prefrontal responses to alcohol odors (AcO). Methods Twenty seven social drinkers (mean age = 25.2, 14 males) had six fMRI scans while viewing negative, neutral, or positive mood images (3 mood conditions) during intermittent exposure to AcO and appetitive control (AppCo) aromas. Results Voxel-wise analyses (p < 0.001) confirmed [AcO > AppCo] activation throughout medial (mPFC) and ventromedial prefrontal regions (vmPFC). Extracted from a priori mPFC and vmPFC regions, and analyzed in Odor (AcO, AppCo) × Mood factorial models, AcO activation was greater than AppCo in left vmPFC (p < 0.001), left mPFC (p = 0.002), and right vmPFC (p = 0.01) regions. Mood did not interact significantly with activation but the covariate of trait negative urgency accounted for significant variance in left vmPFC (p = 0.01) and right vmPFC (p = 0.01) [AcO > AppCo] activation. Negative urgency also mediated the relationship between vmPFC activation and both (1) subjective craving and (2) problematic drinking. Conclusion The trait of negative urgency is associated with neural responses to alcohol cues in the vmPFC, a region involved in reward value and emotion-guided decision-making. This suggests that negative urgency might alter subjective craving and brain regions involved in coding reward value. PMID:24164291
Abnormal ERD/ERS but unaffected BOLD response in patients with Unverricht-Lundborg disease during index extension: a simultaneous EEG-fMRI study.
Visani, E; Minati, L; Canafoglia, L; Gilioli, I; Granvillano, A; Varotto, G; Aquino, D; Fazio, P; Bruzzone, M G; Franceschetti, S; Panzica, F
Electrophysiological studies indicate that Unverricht-Lundborg's disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI.
Monkey cortex through fMRI glasses.
Vanduffel, Wim; Zhu, Qi; Orban, Guy A
In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging.
The physics of functional magnetic resonance imaging (fMRI)
Buxton, Richard B
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology. PMID:24006360
The role of the DLPFC in inductive reasoning of MCI patients and normal agings: an fMRI study.
Yang, YanHui; Liang, PeiPeng; Lu, ShengFu; Li, KunCheng; Zhong, Ning
Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal aging, and whether the activation pattern of this region was different between MCI patients and normal aging. The fMRI results indicated that MCI patients had no difference from normal aging in behavior performance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD response of the DLPFC region for MCI patients was weaker than that for normal aging, and the functional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal aging. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of aging, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.
Pupil diameter covaries with BOLD activity in human locus coeruleus.
Murphy, Peter R; O'Connell, Redmond G; O'Sullivan, Michael; Robertson, Ian H; Balsters, Joshua H
The locus coeruleus-noradrenergic (LC-NA) neuromodulatory system has been implicated in a broad array of cognitive processes, yet scope for investigating this system's function in humans is currently limited by an absence of reliable non-invasive measures of LC activity. Although pupil diameter has been employed as a proxy measure of LC activity in numerous studies, empirical evidence for a relationship between the two is lacking. In the present study, we sought to rigorously probe the relationship between pupil diameter and BOLD activity localized to the human LC. Simultaneous pupillometry and fMRI revealed a relationship between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC, as localized via neuromelanin-sensitive structural imaging and an LC atlas. This relationship was present both at rest and during performance of a two-stimulus oddball task, with and without spatial smoothing of the fMRI data, and survived retrospective image correction for physiological noise. Furthermore, the spatial extent of this pupil/LC relationship guided a volume-of-interest analysis in which we provide the first demonstration in humans of a fundamental characteristic of animal LC activity: phasic modulation by oddball stimulus relevance. Taken together, these findings highlight the potential for utilizing pupil diameter to achieve a more comprehensive understanding of the role of the LC-NA system in human cognition.
BOLD delay times using group delay in sickle cell disease
NASA Astrophysics Data System (ADS)
Coloigner, Julie; Vu, Chau; Bush, Adam; Borzage, Matt; Rajagopalan, Vidya; Lepore, Natasha; Wood, John
Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay times between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. In a group comparison analysis with control subjects, BOLD changes in these areas were found to be almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggest that sickle cell disease causes blood propagation modifications, and that these changes could be used as a biomarker of vascular damage.
Post-stroke aphasia recovery assessed with fMRI and a picture identification task
Szaflarski, Jerzy P.; Eaton, Kenneth; Ball, Angel L.; Banks, Christi; Vannest, Jennifer; Allendorfer, Jane B.; Page, Stephen; Holland, Scott K.
Background Stroke patients often display deficits in language function such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of post-stroke language recovery using a picture identification task during fMRI at 4T. Material and Methods 4 healthy and 4 left MCA stroke subjects with chronic (>1 year) aphasia. Ten fMRI scans were performed for each subject over a 10-week period using a picture identification task. Active condition involved presenting subjects with a panel of 4 figures (e.g., drawings of 4 animals) every 6 seconds; subjects indicated which figure matched the written name in the center. Control condition was same/different judgment task of pairs of geometric figures (squares, octagons or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each; responses were recorded. Results Patients and controls exhibited similar demographic characteristics: age (46 vs. 53 years), personal handedness (EHI; 89 vs. 95), familial handedness (93 vs. 95) or years of education (14.3 vs. 14.8). For the active condition, controls performed better than patients (97.7% vs. 89.1%, p<0.001); performance was similar for the control condition (99.5% vs. 98.8%, p=0.23). During fMRI, controls exhibited bilateral, L>R positive blood oxygenation-level dependent (BOLD) activations in frontal and temporal language areas and symmetric retro-splenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral fronto-temporal language networks. However, the patient group showed positive BOLD activations predominantly in peri-stroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both the control and patient groups displayed high activation reliability (as measured by the ICC) in left frontal and temporal language areas, although the ICC in frontal regions of the patients was spread over a much larger peri-stroke area. Conclusion This study documents the utility
Computing moment-to-moment BOLD activation for real-time neurofeedback.
Hinds, Oliver; Ghosh, Satrajit; Thompson, Todd W; Yoo, Julie J; Whitfield-Gabrieli, Susan; Triantafyllou, Christina; Gabrieli, John D E
Estimating moment-to-moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain-machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment-to-moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment-to-moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI time series, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method.
Perceptual learning of motion direction discrimination with suppressed and unsuppressed MT in humans: an fMRI study.
Thompson, Benjamin; Tjan, Bosco S; Liu, Zili
The middle temporal area of the extrastriate visual cortex (area MT) is integral to motion perception and is thought to play a key role in the perceptual learning of motion tasks. We have previously found, however, that perceptual learning of a motion discrimination task is possible even when the training stimulus contains locally balanced, motion opponent signals that putatively suppress the response of MT. Assuming at least partial suppression of MT, possible explanations for this learning are that 1) training made MT more responsive by reducing motion opponency, 2) MT remained suppressed and alternative visual areas such as V1 enabled learning and/or 3) suppression of MT increased with training, possibly to reduce noise. Here we used fMRI to test these possibilities. We first confirmed that the motion opponent stimulus did indeed suppress the BOLD response within hMT+ compared to an almost identical stimulus without locally balanced motion signals. We then trained participants on motion opponent or non-opponent stimuli. Training with the motion opponent stimulus reduced the BOLD response within hMT+ and greater reductions in BOLD response were correlated with greater amounts of learning. The opposite relationship between BOLD and behaviour was found at V1 for the group trained on the motion-opponent stimulus and at both V1 and hMT+ for the group trained on the non-opponent motion stimulus. As the average response of many cells within MT to motion opponent stimuli is the same as their response to non-directional flickering noise, the reduced activation of hMT+ after training may reflect noise reduction.
Abnormal perilesional BOLD signal is not correlated with stroke patients' behavior
de Haan, Bianca; Rorden, Chris; Karnath, Hans-Otto
Several functional magnetic resonance imaging (fMRI) studies of acute stroke have reported that patients with behavioral deficits show abnormal signal in intact regions of the damaged hemisphere close to the lesion border relative to homologous regions of the patient's intact hemisphere (causing an interhemispheric imbalance) as well as analogous regions in healthy controls. These effects have been interpreted as demonstrating a causal relationship between the abnormal fMRI signal and the pathological behavior. Here we explore an alternative explanation: perhaps the abnormal Blood-Oxygenation Level Dependent (BOLD) fMRI signal is merely a function of distance from the acute lesion. To investigate this hypothesis, we examined three patients with an acute right hemisphere cortical stroke who did not show any overt behavioral deficits, as well as nine healthy elderly controls. We acquired fMRI data while the participants performed a simple visual orientation judgment task. In patients, we observed an abnormal interhemispheric balance consisting of lower levels of percent signal change in perilesional areas of the damaged hemisphere relative to homologous areas in neurologically healthy controls. This suggests that the physiological changes and corresponding interhemispheric imbalance detected by fMRI BOLD in acute stroke observed close to the lesion border may not necessarily reflect changes in the neural function, nor necessarily influence the individuals' (e.g., attentional) behavior. PMID:24137123
Anterior cingulate and the monitoriing of response conflict: evidence from an fMRI study of overt verb generation.
Barch, D M; Braver, T S; Sabb, F W; Noll, D C
Studies of a range of higher cognitive functions consistently activate a region of anterior cingulate cortex (ACC), typically posterior to the genu and superior to the corpus collosum. In particular, this ACC region appears to be active in task situations where there is a need to override a prepotent response tendency, when responding is underdetermined, and when errors are made. We have hypothesized that the function of this ACC region is to monitor for the presence of "crosstalk" or competition between incompatible responses. In prior work, we provided initial support for this hypothesis, demonstrating ACC activity in the same region both during error trials and during correct trials in task conditions designed to elicit greater response competition. In the present study, we extend our testing of this hypothesis to task situations involving underdetermined responding. Specifically, 14 healthy control subjects performed a verb-generation task during event-related functional magnetic resonance imaging (fMRI), with the on-line acquisition of overt verbal responses. The results demonstrated that the ACC, and only the ACC, was more active in a series of task conditions that elicited competition among alternative responses. These conditions included a greater ACC response to: (1) Nouns categorized as low vs. high constraint (i.e., during a norming study, multiple verbs were produced with equal frequency vs. a single verb that produced much more frequently than any other); (2) the production of verbs that were weak associates, rather than, strong associates of particular nouns; and (3) the production of verbs that were weak associates for nouns categorized as high constraint. We discuss the implication of these results for understanding the role that the ACC plays in human cognition.
Predicting the Multisensory Consequences of One's Own Action: BOLD Suppression in Auditory and Visual Cortices
van Kemenade, Bianca M.; Arikan, B. Ezgi; Fiehler, Katja; Leube, Dirk T.; Harris, Laurence R.; Kircher, Tilo
Predictive mechanisms are essential to successfully interact with the environment and to compensate for delays in the transmission of neural signals. However, whether and how we predict multisensory action outcomes remains largely unknown. Here we investigated the existence of multisensory predictive mechanisms in a context where actions have outcomes in different modalities. During fMRI data acquisition auditory, visual and auditory-visual stimuli were presented in active and passive conditions. In the active condition, a self-initiated button press elicited the stimuli with variable short delays (0-417ms) between action and outcome, and participants had to detect the presence of a delay for auditory or visual outcome (task modality). In the passive condition, stimuli appeared automatically, and participants had to detect the number of stimulus modalities (unimodal/bimodal). For action consequences compared to identical but unpredictable control stimuli we observed suppression of the blood oxygen level depended (BOLD) response in a broad network including bilateral auditory and visual cortices. This effect was independent of task modality or stimulus modality and strongest for trials where no delay was detected (undetected
Neural Response during the Activation of the Attachment System in Patients with Borderline Personality Disorder: An fMRI Study.
Buchheim, Anna; Erk, Susanne; George, Carol; Kächele, Horst; Martius, Philipp; Pokorny, Dan; Spitzer, Manfred; Walter, Henrik
Individuals with borderline personality disorder (BPD) are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Eleven female patients with BPD without posttraumatic stress disorder (PTSD) and 17 healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System (AAP), an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for 2 min. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex (DLPFC) and the rostral cingulate zone (RCZ). We interpret this as a neural signature of BPD patients' inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear.
Neural Response during the Activation of the Attachment System in Patients with Borderline Personality Disorder: An fMRI Study
Buchheim, Anna; Erk, Susanne; George, Carol; Kächele, Horst; Martius, Philipp; Pokorny, Dan; Spitzer, Manfred; Walter, Henrik
Individuals with borderline personality disorder (BPD) are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Eleven female patients with BPD without posttraumatic stress disorder (PTSD) and 17 healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System (AAP), an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for 2 min. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex (DLPFC) and the rostral cingulate zone (RCZ). We interpret this as a neural signature of BPD patients' inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear. PMID:27531977
The Response of the Left Ventral Attentional System to Invalid Targets and its Implication for the Spatial Neglect Syndrome: a Multivariate fMRI Investigation.
Silvetti, Massimo; Lasaponara, Stefano; Lecce, Francesca; Dragone, Alessio; Macaluso, Emiliano; Doricchi, Fabrizio
In humans, invalid visual targets that mismatch spatial expectations induced by attentional cues are considered to selectively engage a right hemispheric "reorienting" network that includes the temporal parietal junction (TPJ), the inferior frontal gyrus (IFG), and the medial frontal gyrus (MFG). However, recent findings suggest that this hemispheric dominance is not absolute and that it is rather observed because the TPJ and IFG areas in the left hemisphere are engaged both by invalid and valid cued targets. Because of this, the BOLD response of the left hemisphere to invalid targets is usually cancelled out by the standard "invalid versus valid" contrast used in functional magnetic resonance imaging investigations of spatial attention. Here, we used multivariate pattern recognition analysis (MVPA) to gain finer insight into the role played by the left TPJ and IFG in reorienting to invalid targets. We found that in left TPJ and IFG blood oxygen level-dependent (BOLD) responses to invalid and valid targets were associated to different patterns of neural activity, possibly reflecting the presence of functionally distinct neuronal populations. Pattern segregation was significant at group level, it was present in almost all of the participants to the study and was observed both for targets in the left and right side of space. A control whole-brain MVPA ("Searchlight" analysis) confirmed the results obtained in predefined regions of interest and highlighted that also other areas, that is, superior parietal and frontal-polar cortex, show different patterns of BOLD response to valid and invalid targets. These results confirm and expand previous evidence highlighting the involvement of the left hemisphere in reorienting of visual attention (Doricchi et al. 2010; Dragone et al. 2015). These findings suggest that asymmetrical reorienting deficits suffered by right brain damaged patients with left spatial neglect, who have severe impairments in contralesional reorienting and
Functional connectivity in BOLD and CBF data: Similarity and reliability of resting brain networks
Jann, Kay; Gee, Dylan G.; Kilroy, Emily; Schwab, Simon; Smith, Robert X.; Cannon, Tyrone D.; Wang, Danny J.J.
Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2 × 2 × 2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test–retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905 ± 0.033 between-sessions; 0.885 ± 0.052 between-scanners) than ASL (0.545 ± 0.048; 0.575 ± 0.059). Nevertheless, ASL provided highly reproducible (0.955 ± 0.021; 0.970 ± 0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners. PMID:25463468
Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.
Yuan, Han; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy
Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These
From blood oxygenation level dependent (BOLD) signals to brain temperature maps.
Sotero, Roberto C; Iturria-Medina, Yasser
A theoretical framework is presented for converting Blood Oxygenation Level Dependent (BOLD) images to brain temperature maps, based on the idea that disproportional local changes in cerebral blood flow (CBF) as compared with cerebral metabolic rate of oxygen consumption (CMRO₂) during functional brain activity, lead to both brain temperature changes and the BOLD effect. Using an oxygen limitation model and a BOLD signal model, we obtain a transcendental equation relating CBF and CMRO₂ changes with the corresponding BOLD signal, which is solved in terms of the Lambert W function. Inserting this result in the dynamic bioheat equation describing the rate of temperature changes in the brain, we obtain a nonautonomous ordinary differential equation that depends on the BOLD response, which is solved numerically for each brain voxel. Temperature maps obtained from a real BOLD dataset registered in an attention to visual motion experiment were calculated, obtaining temperature variations in the range: (-0.15, 0.1) which is consistent with experimental results. The statistical analysis revealed that significant temperature activations have a similar distribution pattern than BOLD activations. An interesting difference was the activation of the precuneus in temperature maps, a region involved in visuospatial processing, an effect that was not observed on BOLD maps. Furthermore, temperature maps were more localized to gray matter regions than the original BOLD maps, showing less activated voxels in white matter and cerebrospinal fluid.
Age differences in the motor control of speech: An fMRI study of healthy aging.
Tremblay, Pascale; Sato, Marc; Deschamps, Isabelle
Healthy aging is associated with a decline in cognitive, executive, and motor processes that are concomitant with changes in brain activation patterns, particularly at high complexity levels. While speech production relies on all these processes, and is known to decline with age, the mechanisms that underlie these changes remain poorly understood, despite the importance of communication on everyday life. In this cross-sectional group study, we investigated age differences in the neuromotor control of speech production by combining behavioral and functional magnetic resonance imaging (fMRI) data. Twenty-seven healthy adults underwent fMRI while performing a speech production task consisting in the articulation of nonwords of different sequential and motor complexity. Results demonstrate strong age differences in movement time (MT), with longer and more variable MT in older adults. The fMRI results revealed extensive age differences in the relationship between BOLD signal and MT, within and outside the sensorimotor system. Moreover, age differences were also found in relation to sequential complexity within the motor and attentional systems, reflecting both compensatory and de-differentiation mechanisms. At very high complexity level (high motor complexity and high sequence complexity), age differences were found in both MT data and BOLD response, which increased in several sensorimotor and executive control areas. Together, these results suggest that aging of motor and executive control mechanisms may contribute to age differences in speech production. These findings highlight the importance of studying functionally relevant behavior such as speech to understand the mechanisms of human brain aging. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Strategies for block-design fMRI experiments during task-related motion of structures of the oral cavity.
Soltysik, David A; Hyde, James S
Functional MRI (fMRI) studies of jaw motion, speech, and swallowing disorders have been hampered by motion artifacts. Tissue motion perturbs the static magnetic field, creating geometric distortions in echo-planar images that lead to many false positives in activation maps. These problems have restricted blood oxygenation level-dependent (BOLD) fMRI studies involving orofacial muscles to event-related designs, which offer weak contrast-to-noise ratios when compared to block designs. Two new approaches are described that greatly reduce false positives in the activation maps created by the distortions in block-design fMRI studies involving jaw and tongue motion during chewing. First, an appropriate task duration of 10-14 s was found to maximize functional contrast while minimizing motion artifacts. Second, three motion-sensitive postprocessing methods were applied successively to examine the temporal and spatial characteristics of responses and identify and remove false positives caused by motion artifacts. These techniques are shown to allow the use of block design in an fMRI study of a jaw motion task. Extension to speech and swallowing tasks is discussed.
Quantitative fMRI and oxidative neuroenergetics
Hyder, Fahmeed; Rothman, Douglas L.
The discovery of functional magnetic resonance imaging (fMRI) has greatly impacted neuroscience. The blood oxygenation level-dependent (BOLD) signal, using deoxyhemoglobin as an endogenous paramagnetic contrast agent, exposes regions of interest in task-based and resting-state paradigms. However the BOLD contrast is at best a partial measure of neuronal activity, because the functional maps obtained by differencing or correlations ignore the total neuronal activity in the baseline state. Here we describe how studies of brain energy metabolism at Yale, especially with 13C magnetic resonance spectroscopy and related techniques, contributed to development of quantitative functional brain imaging with fMRI by providing a reliable measurement of baseline energy. This narrative takes us on a journey, from molecules to mind, with illuminating insights about neuronal-glial activities in relation to energy demand of synaptic activity. These results, along with key contributions from laboratories worldwide, comprise the energetic basis for quantitative interpretation of fMRI data. PMID:22542993
Category search speeds up face-selective fMRI responses in a non-hierarchical cortical face network.
Jiang, Fang; Badler, Jeremy B; Righi, Giulia; Rossion, Bruno
The human brain is extremely efficient at detecting faces in complex visual scenes, but the spatio-temporal dynamics of this remarkable ability, and how it is influenced by category-search, remain largely unknown. In the present study, human subjects were shown gradually-emerging images of faces or cars in visual scenes, while neural activity was recorded using functional magnetic resonance imaging (fMRI). Category search was manipulated by the instruction to indicate the presence of either a face or a car, in different blocks, as soon as an exemplar of the target category was detected in the visual scene. The category selectivity of most face-selective areas was enhanced when participants were instructed to report the presence of faces in gradually decreasing noise stimuli. Conversely, the same regions showed much less selectivity when participants were instructed instead to detect cars. When "face" was the target category, the fusiform face area (FFA) showed consistently earlier differentiation of face versus car stimuli than did the "occipital face area" (OFA). When "car" was the target category, only the FFA showed differentiation of face versus car stimuli. These observations provide further challenges for hierarchical models of cortical face processing and show that during gradual revealing of information, selective category-search may decrease the required amount of information, enhancing and speeding up category-selective responses in the human brain.
The stimuli drive the response: an fMRI study of youth processing adult or child emotional face stimuli.
Marusak, Hilary A; Carré, Justin M; Thomason, Moriah E
Effective navigation of the social world relies on the correct interpretation of facial emotions. This may be particularly important in formative years. Critically, literature examining the emergence of face processing in youth (children and adolescents) has focused on the neural and behavioral correlates of processing adult faces, which are relationally different from youth participants, and whose facial expressions may convey different meaning than faces of their peers. During a functional magnetic resonance imaging (fMRI) scan, we compared concurrent neural and behavioral responses as youth (N=25) viewed validated, emotionally varied (i.e., anger, fear, happy, and neutral) adult and child face stimuli. We observed that participants made fewer errors when matching adult, compared to child, face stimuli, and that while similar brain regions were involved in processing both adult and child faces, activation in the face processing neural network was greater for adult than child faces. This was true across emotions, and also when comparing neutral adult versus neutral child faces. Additionally, a valence by stimuli-type effect was observed within the amygdala. That is, within adult face stimuli, negative and neutral face stimuli elicited the largest effects, whereas within child face stimuli, happy face stimuli elicited the largest amygdala effects. Thus, heightened engagement of the amygdala was observed for happy child and angry adult faces, which may reflect age-specific salience of select emotions in early life. This study provides evidence that the relational age of the perceived face influences neural processing in youth.
BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive Aging.
Guitart-Masip, Marc; Salami, Alireza; Garrett, Douglas; Rieckmann, Anna; Lindenberger, Ulman; Bäckman, Lars
Dopamine (DA) losses are associated with various aging-related cognitive deficits. Typically, higher moment-to-moment brain signal variability in large-scale patterns of voxels in neocortical regions is linked to better cognitive performance and younger adult age, yet the physiological mechanisms regulating brain signal variability are unknown. We explored the relationship among adult age, DA availability, and blood oxygen level-dependent (BOLD) signal variability, while younger and older participants performed a spatial working memory (SWM) task. We quantified striatal and extrastriatal DA D1 receptor density with [(11)C]SCH23390 and positron emission tomography in all participants. We found that BOLD variability in a neocortical region was negatively related to age and positively related to SWM performance. In contrast, BOLD variability in subcortical regions and bilateral hippocampus was positively related to age and slower responses, and negatively related to D1 density in caudate and dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical regions was positively associated with task-related disengagement of the default-mode network, a network whose activation needs to be suppressed for efficient SWM processing. Our results show that age-related DA losses contribute to changes in brain signal variability in subcortical regions and suggest a potential mechanism, by which neocortical BOLD variability supports cognitive performance.
Calibrated BOLD using direct measurement of changes in venous oxygenation.
Driver, Ian D; Hall, Emma L; Wharton, Samuel J; Pritchard, Susan E; Francis, Susan T; Gowland, Penny A
Calibration of the BOLD signal is potentially of great value in providing a closer measure of the underlying changes in brain function related to neuronal activity than the BOLD signal alone, but current approaches rely on an assumed relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF). This is poorly characterised in humans and does not reflect the predominantly venous nature of BOLD contrast, whilst this relationship may vary across brain regions and depend on the structure of the local vascular bed. This work demonstrates a new approach to BOLD calibration which does not require an assumption about the relationship between cerebral blood volume and cerebral blood flow. This method involves repeating the same stimulus both at normoxia and hyperoxia, using hyperoxic BOLD contrast to estimate the relative changes in venous blood oxygenation and venous CBV. To do this the effect of hyperoxia on venous blood oxygenation has to be calculated, which requires an estimate of basal oxygen extraction fraction, and this can be estimated from the phase as an alternative to using a literature estimate. Additional measurement of the relative change in CBF, combined with the blood oxygenation change can be used to calculate the relative change in CMRO(2) due to the stimulus. CMRO(2) changes of 18 ± 8% in response to a motor task were measured without requiring the assumption of a CBV/CBF coupling relationship, and are in agreement with previous approaches.
Repetition suppression: a means to index neural representations using BOLD?
Behrens, Timothy E. J.
Understanding how the human brain gives rise to complex cognitive processes remains one of the biggest challenges of contemporary neuroscience. While invasive recording in animal models can provide insight into neural processes that are conserved across species, our understanding of cognition more broadly relies upon investigation of the human brain itself. There is therefore an imperative to establish non-invasive tools that allow human brain activity to be measured at high spatial and temporal resolution. In recent years, various attempts have been made to refine the coarse signal available in functional magnetic resonance imaging (fMRI), providing a means to investigate neural activity at the meso-scale, i.e. at the level of neural populations. The most widely used techniques include repetition suppression and multivariate pattern analysis. Human neuroscience can now use these techniques to investigate how representations are encoded across neural populations and transformed by relevant computations. Here, we review the physiological basis, applications and limitations of fMRI repetition suppression with a brief comparison to multivariate techniques. By doing so, we show how fMRI repetition suppression holds promise as a tool to reveal complex neural mechanisms that underlie human cognitive function. This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574308
Regional Homogeneity of Resting-state fMRI Contributes to Both Neurovascular and Task Activation Variations
Yuan, Rui; Di, Xin; Kim, Eun H.; Barik, Sabrina; Rypma, Bart; Biswal, Bharat B.
The task induced blood oxygenation level dependent signal changes observed using functional magnetic resonance imaging (fMRI) is critically dependent on the relationship between neuronal activity and hemodynamic response. Therefore, understanding the nature of neurovascular coupling is important when interpreting fMRI signal changes evoked via task. In this study, we used regional homogeneity (ReHo), a measure of local synchronization of the BOLD time series, to investigate whether the similarities of one voxel with the surrounding voxels is a property of neurovascular coupling. FMRI scans were obtained from fourteen subjects during bilateral finger tapping (FTAP), digit-symbol substitution (DSST) and periodic breath holding (BH) paradigm. A resting-state scan was also obtained for each of the subjects for 4 minutes using identical imaging parameters. Inter-voxel correlation analyses were conducted between the resting-state ReHo, resting-state amplitude of low frequency fluctuations (ALFF), breath hold (BH) responses and task activations within the masks related to task activations. There was a reliable mean voxel-wise spatial correlation between ReHo and other neurovascular variables (BH responses and ALFF). We observed a moderate correlation between ReHo and task activations (FTAP: r = 0.32; DSST: r = 0.22) within the task positive network and a small yet reliable correlation within the default mode network (DSST: r = −0.08). Subsequently, a linear regression was used to estimate the contribution of ReHo, ALFF and BH responses to the task activated voxels. The unique contribution of ReHo was minimal. The results suggest that regional synchrony of the BOLD activity is a property that can explain the variance of neurovascular coupling and task activations; but its contribution to task activations can be accounted for by other neurovascular factors such as the ALFF. PMID:23969197
Silent speechreading in the absence of scanner noise: an event-related fMRI study.
MacSweeney, M; Amaro, E; Calvert, G A; Campbell, R; David, A S; McGuire, P; Williams, S C; Woll, B; Brammer, M J
In a previous study we used functional magnetic resonance imaging (fMRI) to demonstrate activation in auditory cortex during silent speechreading. Since image acquisition during fMRI generates acoustic noise, this pattern of activation could have reflected an interaction between background scanner noise and the visual lip-read stimuli. In this study we employed an event-related fMRI design which allowed us to measure activation during speechreading in the absence of acoustic scanner noise. In the experimental condition, hearing subjects were required to speechread random numbers from a silent speaker. In the control condition subjects watched a static image of the same speaker with mouth closed and were required to subvocally count an intermittent visual cue. A single volume of images was collected to coincide with the estimated peak of the blood oxygen level dependent (BOLD) response to these stimuli across multiple baseline and experimental trials. Silent speechreading led to greater activation in lateral temporal cortex relative to the control condition. This indicates that activation of auditory areas during silent speechreading is not a function of acoustic scanner noise and confirms that silent speechreading engages similar regions of auditory cortex as listening to speech.
A kernel machine-based fMRI physiological noise removal method.
Song, Xiaomu; Chen, Nan-kuei; Gaur, Pooja
Functional magnetic resonance imaging (fMRI) technique with blood oxygenation level dependent (BOLD) contrast is a powerful tool for noninvasive mapping of brain function under task and resting states. The removal of cardiac- and respiration-induced physiological noise in fMRI data has been a significant challenge as fMRI studies seek to achieve higher spatial resolutions and characterize more subtle neuronal changes. The low temporal sampling rate of most multi-slice fMRI experiments often causes aliasing of physiological noise into the frequency range of BOLD activation signal. In addition, changes of heartbeat and respiration patterns also generate physiological fluctuations that have similar frequencies with BOLD activation. Most existing physiological noise-removal methods either place restrictive limitations on image acquisition or utilize filtering or regression based post-processing algorithms, which cannot distinguish the frequency-overlapping BOLD activation and the physiological noise. In this work, we address the challenge of physiological noise removal via the kernel machine technique, where a nonlinear kernel machine technique, kernel principal component analysis, is used with a specifically identified kernel function to differentiate BOLD signal from the physiological noise of the frequency. The proposed method was evaluated in human fMRI data acquired from multiple task-related and resting state fMRI experiments. A comparison study was also performed with an existing adaptive filtering method. The results indicate that the proposed method can effectively identify and reduce the physiological noise in fMRI data. The comparison study shows that the proposed method can provide comparable or better noise removal performance than the adaptive filtering approach.
A Kernel Machine-based fMRI Physiological Noise Removal Method
Song, Xiaomu; Chen, Nan-kuei; Gaur, Pooja
Functional magnetic resonance imaging (fMRI) technique with blood oxygenation level dependent (BOLD) contrast is a powerful tool for noninvasive mapping of brain function under task and resting states. The removal of cardiac- and respiration-induced physiological noise in fMRI data has been a significant challenge as fMRI studies seek to achieve higher spatial resolutions and characterize more subtle neuronal changes. The low temporal sampling rate of most multi-slice fMRI experiments often causes aliasing of physiological noise into the frequency range of BOLD activation signal. In addition, changes of heartbeat and respiration patterns also generate physiological fluctuations that have similar frequencies with BOLD activation. Most existing physiological noise-removal methods either place restrictive limitations on image acquisition or utilize filtering or regression based post-processing algorithms, which cannot distinguish the frequency-overlapping BOLD activation and the physiological noise. In this work, we address the challenge of physiological noise removal via the kernel machine technique, where a nonlinear kernel machine technique, kernel principal component analysis, is used with a specifically identified kernel function to differentiate BOLD signal from the physiological noise of the frequency. The proposed method was evaluated in human fMRI data acquired from multiple task-related and resting state fMRI experiments. A comparison study was also performed with an existing adaptive filtering method. The results indicate that the proposed method can effectively identify and reduce the physiological noise in fMRI data. The comparison study shows that the proposed method can provide comparable or better noise removal performance than the adaptive filtering approach. PMID:24321306
Effects of citalopram and escitalopram on fMRI response to affective stimuli in healthy volunteers selected by serotonin transporter genotype
Henry, Michael E.; Lauriat, Tara L.; Lowen, Steven B.; Churchill, Jeffrey H.; Hodgkinson, Colin A.; Goldman, David; Renshaw, Perry F.
This study was designed to assess whether functional magnetic resonance imaging (fMRI) following antidepressant administration (pharmaco-fMRI) is sufficiently sensitive to detect differences in patterns of activation between enantiomers of the same compound. Healthy adult males (n = 11) participated in a randomized, double-blind, cross-over trial with three medication periods during which they received citalopram (racemic mixture), escitalopram (S-citalopram alone), or placebo for 2 weeks. All participants had high expression serotonin transporter genotypes. An fMRI scan that included passive viewing of overt and covert affective faces and affective words was performed after each medication period. Activation in response to overt faces was greater following escitalopram than following citalopram in the right insula, thalamus, and putamen when the faces were compared with a fixation stimulus. For the rapid covert presentation, a greater response was observed in the left middle temporal gyrus in the happy versus fearful contrast following escitalopram than following citalopram. Thus, the combination of genomics and fMRI was successful in discriminating between two very similar drugs. However, the pattern of activation observed suggests that further studies are indicated to understand how to optimally combine the two techniques. PMID:23845563
Effects of citalopram and escitalopram on fMRI response to affective stimuli in healthy volunteers selected by serotonin transporter genotype.
Henry, Michael E; Lauriat, Tara L; Lowen, Steven B; Churchill, Jeffrey H; Hodgkinson, Colin A; Goldman, David; Renshaw, Perry F
This study was designed to assess whether functional magnetic resonance imaging (fMRI) following antidepressant administration (pharmaco-fMRI) is sufficiently sensitive to detect differences in patterns of activation between enantiomers of the same compound. Healthy adult males (n=11) participated in a randomized, double-blind, cross-over trial with three medication periods during which they received citalopram (racemic mixture), escitalopram (S-citalopram alone), or placebo for 2 weeks. All participants had high expression serotonin transporter genotypes. An fMRI scan that included passive viewing of overt and covert affective faces and affective words was performed after each medication period. Activation in response to overt faces was greater following escitalopram than following citalopram in the right insula, thalamus, and putamen when the faces were compared with a fixation stimulus. For the rapid covert presentation, a greater response was observed in the left middle temporal gyrus in the happy versus fearful contrast following escitalopram than following citalopram. Thus, the combination of genomics and fMRI was successful in discriminating between two very similar drugs. However, the pattern of activation observed suggests that further studies are indicated to understand how to optimally combine the two techniques.
Differential cerebral response to somatosensory stimulation of an acupuncture point vs. two non-acupuncture points measured with EEG and fMRI
Nierhaus, Till; Pach, Daniel; Huang, Wenjing; Long, Xiangyu; Napadow, Vitaly; Roll, Stephanie; Liang, Fanrong; Pleger, Burkhard; Villringer, Arno; Witt, Claudia M.
Acupuncture can be regarded as a complex somatosensory stimulation. Here, we evaluate whether the point locations chosen for a somatosensory stimulation with acupuncture needles differently change the brain activity in healthy volunteers. We used EEG, event-related fMRI, and resting-state functional connectivity fMRI to assess neural responses to standardized needle stimulation of the acupuncture point ST36 (lower leg) and two control point locations (CP1 same dermatome, CP2 different dermatome). Cerebral responses were expected to differ for stimulation in two different dermatomes (CP2 different from ST36 and CP1), or stimulation at the acupuncture point vs. the control points. For EEG, mu rhythm power increased for ST36 compared to CP1 or CP2, but not when comparing the two control points. The fMRI analysis found more pronounced insula and S2 (secondary somatosensory cortex) activation, as well as precuneus deactivation during ST36 stimulation. The S2 seed-based functional connectivity analysis revealed increased connectivity to right precuneus for both comparisons, ST36 vs. CP1 and ST36 vs. CP2, however in different regions. Our results suggest that stimulation at acupuncture points may modulate somatosensory and saliency processing regions more readily than stimulation at non-acupuncture point locations. Also, our findings suggest potential modulation of pain perception due to acupuncture stimulation. PMID:25741269
Differential cerebral response to somatosensory stimulation of an acupuncture point vs. two non-acupuncture points measured with EEG and fMRI.
Nierhaus, Till; Pach, Daniel; Huang, Wenjing; Long, Xiangyu; Napadow, Vitaly; Roll, Stephanie; Liang, Fanrong; Pleger, Burkhard; Villringer, Arno; Witt, Claudia M
Acupuncture can be regarded as a complex somatosensory stimulation. Here, we evaluate whether the point locations chosen for a somatosensory stimulation with acupuncture needles differently change the brain activity in healthy volunteers. We used EEG, event-related fMRI, and resting-state functional connectivity fMRI to assess neural responses to standardized needle stimulation of the acupuncture point ST36 (lower leg) and two control point locations (CP1 same dermatome, CP2 different dermatome). Cerebral responses were expected to differ for stimulation in two different dermatomes (CP2 different from ST36 and CP1), or stimulation at the acupuncture point vs. the control points. For EEG, mu rhythm power increased for ST36 compared to CP1 or CP2, but not when comparing the two control points. The fMRI analysis found more pronounced insula and S2 (secondary somatosensory cortex) activation, as well as precuneus deactivation during ST36 stimulation. The S2 seed-based functional connectivity analysis revealed increased connectivity to right precuneus for both comparisons, ST36 vs. CP1 and ST36 vs. CP2, however in different regions. Our results suggest that stimulation at acupuncture points may modulate somatosensory and saliency processing regions more readily than stimulation at non-acupuncture point locations. Also, our findings suggest potential modulation of pain perception due to acupuncture stimulation.
Primary somatosensory contribution to action observation brain activity—combining fMRI and cTBS
Valchev, Nikola; Avenanti, Alessio; Keysers, Christian
Traditionally the mirror neuron system (MNS) only includes premotor and posterior parietal cortices. However, somatosensory cortices, BA1/2 in particular, are also activated during action execution and observation. Here, we examine whether BA1/2 and the parietofrontal MNS integrate information by using functional magnetic resonance imaging (fMRI)-guided continuous theta-burst stimulation (cTBS) to perturb BA1/2. Measuring brain activity using fMRI while participants are under the influence of cTBS shows local cTBS effects in BA1/2 varied, with some participants showing decreases and others increases in the BOLD response to viewing actions vs control stimuli. We show how measuring cTBS effects using fMRI can harness this variance using a whole-brain regression. This analysis identifies brain regions exchanging action-specific information with BA1/2 by mapping voxels away from the coil with cTBS-induced, action-observation-specific BOLD contrast changes that mirror those under the coil. This reveals BA1/2 exchanges action-specific information with premotor, posterior parietal and temporal nodes of the MNS during action observation. Although anatomical connections between BA1/2 and these regions are well known, this is the first demonstration that these connections carry action-specific signals during observation and hence, that BA1/2 plays a causal role in the human MNS. PMID:26979966
A new spatially constrained NMF with application to fMRI.
Ferdowsi, Saideh; Abolghasemi, Vahid; Makkiabadi, Bahador; Sanei, Saeid
In this paper the problem of BOLD detection is addressed. The focus here is on non-negative matrix factorization (NMF), which is a data driven method and able to provide part-based representation of data. A new constrained optimization problem is proposed for the purpose of BOLD detection. The proposed constraint imposes some prior spatial information of active area inside the brain, on the decomposition process. The constraint is built up based on the type of stimulus and available physiological knowledge of the brain performance. The simulation results on both synthetic and real fMRI data show that applying the proposed constraint improves the BOLD detection performance.
Dependence of BOLD signal change on tactile stimulus intensity in SI of primates.
Zhang, Na; Gore, John C; Chen, Li M; Avison, Malcolm J
Recently, we have demonstrated that the fine-digit topography (millimeter sized) previously identified in the primary somatosensory cortex (SI), using electrophysiology and intrinsic signal optical imaging, can also be mapped with submillimeter resolution using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging at high field. In the present study, we have examined the dependence of BOLD signal response on stimulus intensity in two subregions of SI, Areas 3b and 1. In a region(s)-of-interest (ROI) analysis of Area 3b, BOLD signal amplitude increased linearly with increasing amplitude of an 8-Hz vibrotactile stimulus, and BOLD signal was sustained throughout the stimulation period. In contrast, in Area 1, a significant BOLD signal response was only observed with more intense stimuli, and ROI analysis of the dependence of BOLD response showed no significant dependence on stimulus intensity. In addition, activation was not sustained throughout the period of stimulation. Differing responses of Areas 3b and 1 suggest potentially divergent roles for subregions of SI cortices in vibrotactile intensity encoding. Moreover, this study underscores the importance of imaging at small spatial scales. In this case, such high-resolution imaging allows differentiation between area-specific roles in intensity encoding and identifies anatomic targets for detailed electrophysiological studies of somatosensory neuronal populations with different coding properties. These experiments illustrate the value of nonhuman primates for characterizing the dependence of the BOLD signal response on stimulus parameters and on underlying neural response properties.
Differentially Tuned Responses to Restricted versus Prolonged Awareness of Threat: A Preliminary fMRI Investigation
ERIC Educational Resources Information Center
Adams, Reginald B., Jr.; Franklin, Robert G., Jr.; Nelson, Anthony J.; Gordon, Heather L.; Kleck, Robert E.; Whalen, Paul J.; Ambady, Nalini
Responses to threat occur via two known independent processing routes. We propose that early, reflexive processing is predominantly tuned to the detection of congruent combinations of facial cues that signal threat, whereas later, reflective processing is predominantly tuned to incongruent combinations of threat. To test this prediction, we…
Individual Differences in Mathematical Competence Modulate Brain Responses to Arithmetic Errors: An fMRI Study
ERIC Educational Resources Information Center
Ansari, Daniel; Grabner, Roland H.; Koschutnig, Karl; Reishofer, Gernot; Ebner, Franz
Data from both neuropsychological and neuroimaging studies have implicated the left inferior parietal cortex in calculation. Comparatively less attention has been paid to the neural responses associated with the commission of calculation errors and how the processing of arithmetic errors is modulated by individual differences in mathematical…
Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner
Bressler, David W.; Fortenbaugh, Francesca C.; Robertson, Lynn C.; Silver, Michael A.
Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. PMID:23562388
The Neostriatum and Response Selection in Overt Sentence Production: an fMRI Study
Argyropoulos, Georgios P.; Tremblay, Pascale; Small, Steven L.
A number of premotor and prefrontal brain areas have been recently shown to play a significant role in response selection in overt sentence production. These areas are anatomically connected to the basal ganglia, a set of subcortical structures that has been traditionally involved in response selection across behavioral domains. The putamen and the caudate, the two major inputs to the basal ganglia, have been shown to undertake motor- as well as non-motor-related selection operations in language processing. Here we investigate the role of these basal ganglia structures in sentence repetition and generation in healthy adults. Although sentence generation is known to activate prefrontal and premotor cortical areas that reciprocally connect with these two neostriatal structures, their specific contributions are not known. We present evidence suggesting that that the putamen undertakes articulation-related aspects across tasks, while the caudate selectively supports selection processes in sentence generation. PMID:23721723
Dynamics of fMRI signals during human brain activations to a stimulus
NASA Astrophysics Data System (ADS)
Liu, Haiying; Kato, Toshinori; Neves, Carlos
In fMRI memory study, the temporal behavior of BOLD fMRI signals were consistently observed from various brain processing areas at 1.5 Tesla and consistent with the expected functions. Also, all the activations generally exhibit three types of temporal characteristics: short, sustained and delayed responses in relation to the primary stimuli. To address these cerebral multiphasic responses, a suitable functional data analysis scheme has been used, in which the neural response of a specific brain area to a pre-determined stimulation input of some sort was assumed to be linear. The visual memory study was performed on 6 normal subjects on a clinical MR scanner using a 5 min long rapid dynamical whole brain imaging using EPI acquisition during a single memory task, which involved a 45 sec visual presentation of three simple abstract geometric figures to the subject via LCD projector. The results showed that the activations in visual cortex were tightly correlated with the visual stimulus, while the activations detected in interior temporal, entorhinal cortex and inferior temporal area were delayed. Using the new technique, the brian activations were further characterized quantitatively in terms of delay and prolonged response. The resulting effective impulse response functions corresponding to these brain activations revealed much clearly all the temporal components.
Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence.
Soloff, Paul H; White, Richard; Omari, Amro; Ramaseshan, Karthik; Diwadkar, Vaibhav A
Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and the basal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic
Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence
Soloff, Paul H.; White, Richard; Omari, Amro; Ramaseshan, Karthik; Diwadka, Vaibhav A.
Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and thebasal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic
Branding and a child's brain: an fMRI study of neural responses to logos.
Bruce, Amanda S; Bruce, Jared M; Black, William R; Lepping, Rebecca J; Henry, Janice M; Cherry, Joseph Bradley C; Martin, Laura E; Papa, Vlad B; Davis, Ann M; Brooks, William M; Savage, Cary R
Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing.
Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses
Goldstein, Jill M.; Lancaster, Katie; Longenecker, Julia M.; Abbs, Brandon; Holsen, Laura M.; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T.; Buka, Stephen L.; Seidman, Larry J.; Klibanski, Anne
Psychosis involves dysregulation of response to stress, particularly to negative valence stimuli. Functional magnetic resonance imaging studies of psychosis have shown hyperactivity in hypothalamus, hippocampus, amygdala, and anterior cingulate cortex, and orbitofrontal and medial prefrontal cortices. Sex differences in these deficits may be associated with steroid hormone pathway abnormalities, i.e., dysregulation of the hypothalamic pituitary-adrenal and -gondal axes. We predicted abnormal steroid hormone levels in psychosis cases would be associated with hyperactivity in hypothalamus, amygdala, and hippocampus, and hypoactivity in prefrontal and anterior cingulate cortices in a sex-dependent way, with more severe deficits in men than women with psychosis. We studied 32 psychosis cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood throughout functional magnetic resonance imaging procedures. Males with psychosis showed hyperactivity across all hypothesized regions, including the hypothalamus and anterior cingulate cortex by family-wise corrected significance. Females showed hyperactivity in the hippocampus and amygdala and hypoactivity in orbital and medial prefrontal cortices, the latter by family-wise correction. Interaction of case status by sex was significant in the medial prefrontal cortex and, marginally so, in the left orbitofrontal cortex, with female cases (vs. healthy females and males) exhibiting the lowest activity. Male and female cases compared with their healthy counterparts were hypercortisolemic, which was associated with hyperactivity in prefrontal cortices in male cases and hypoactivity in female cases. This was further associated, respectively, with low bioavailable testosterone in male cases and low estradiol in female cases. Findings suggest disruptions in neural-hormone associations in response to stress are sex-dependent in psychosis, particularly in the prefrontal cortex. PMID
Sensory-motor networks involved in speech production and motor control: an fMRI study.
Behroozmand, Roozbeh; Shebek, Rachel; Hansen, Daniel R; Oya, Hiroyuki; Robin, Donald A; Howard, Matthew A; Greenlee, Jeremy D W
Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking.
Characterization and Reduction of Cardiac- and Respiratory-Induced Noise as a Function of the Sampling Rate (TR) in fMRI
Cordes, Dietmar; Nandy, Rajesh R.; Schafer, Scott; Wager, Tor D.
It has recently been shown that both high-frequency and low-frequency cardiac and respiratory noise sources exist throughout the entire brain and can cause significant signal changes in fMRI data. It is also known that the brainstem, basal forebrain and spinal cord area are problematic for fMRI because of the magnitude of cardiac-induced pulsations at these locations. In this study, the physiological noise contributions in the lower brain areas (covering the brainstem and adjacent regions) are investigated and a novel method is presented for computing both low-frequency and high-frequency physiological regressors accurately for each subject. In particular, using a novel optimization algorithm that penalizes curvature (i.e. the second derivative) of the physiological hemodynamic response functions, the cardiac -and respiratory-related response functions are computed. The physiological noise variance is determined for each voxel and the frequency-aliasing property of the high-frequency cardiac waveform as a function of the repetition time (TR) is investigated. It is shown that for the brainstem and other brain areas associated with large pulsations of the cardiac rate, the temporal SNR associated with the low-frequency range of the BOLD response has maxima at subject-specific TRs. At these values, the high-frequency aliased cardiac rate can be eliminated by digital filtering without affecting the BOLD-related signal. PMID:24355483
Differential Brain Responses to Cries of Infants with Autistic Disorder and Typical Development: An fMRI Study
ERIC Educational Resources Information Center
Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H.; de Falco, Simona
This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and…
Analysis of Neural-BOLD Coupling Through Four Models of the Neural Metabolic Demand.
Tyler, Christopher W; Likova, Lora T; Nicholas, Spero C
The coupling of the neuronal energetics to the blood-oxygen-level-dependent (BOLD) response is still incompletely understood. To address this issue, we compared the fits of four plausible models of neurometabolic coupling dynamics to available data for simultaneous recordings of the local field potential and the local BOLD response recorded from monkey primary visual cortex over a wide range of stimulus durations. The four models of the metabolic demand driving the BOLD response were: direct coupling with the overall LFP; rectified coupling to the LFP; coupling with a slow adaptive component of the implied neural population response; and coupling with the non-adaptive intracellular input signal defined by the stimulus time course. Taking all stimulus durations into account, the results imply that the BOLD response is most closely coupled with metabolic demand derived from the intracellular input waveform, without significant influence from the adaptive transients and nonlinearities exhibited by the LFP waveform.
Comparison of fMRI and PEPSI during language processing in children.
Serafini, S; Steury, K; Richards, T; Corina, D; Abbott, R; Dager, S R; Berninger, V
The present study explored the correlation between lactate as detected by MR spectroscopy (MRS) and blood oxygenation level dependent (BOLD) responses in male children during auditory-based language tasks. All subjects (N = 8) participated in one proton echo planar spectroscopic imaging (PEPSI) and one functional magnetic resonance imaging (fMRI) session that required phonological and lexical judgments to aurally presented stimuli. Valid PEPSI data was limited in the frontal areas of the brain due to the magnetic susceptibility of the eye orbits and frontal sinuses. Findings from the remainder of the brain indicate that subjects show a significant consistency across imaging techniques in the left temporal area during the lexical task, but not in any other measurable area or during the phonological task. Magn Reson Med 45:217-225, 2001.
van Gelderen, P.; Duyn, J.H.; Ramsey, N.F.; Liu, G.; Moonen, C.T.W.
In the early days of BOLD fMRI, the acquisition of T2* weighted data was greatly facilitated by rapid scan techniques such as EPI. The latter, however, was only available on a few MRI systems that were equipped with specialized hardware that allowed rapid switching of the imaging gradients. For this reason, soon after the invention of fMRI, the scan technique PRESTO was developed to make rapid T2* weighted scanning available on standard clinical scanning. This method combined echo shifting, which allows for echo times longer than the sequence repetition time, with acquisition of multiple k-space lines per excitation. These two concepts were combined in order to achieve a method fast enough for fMRI, while maintaining a sufficiently long echo time for optimal contrast. PRESTO has been primarily used for 3D scanning, which minimized the contribution of large vessels due to inflow effects. Although PRESTO is still being used today, its appeal has lessened somewhat due to increased gradient performance of modern MRI scanners. Compared to 2D EPI, PRESTO may have somewhat reduced temporal stability, which is a disadvantage for fMRI that may not outweigh the advantage of reduced inflow effects provided by 3D scanning. In this overview, the history of the development of the PRESTO is presented, followed by a qualitative comparison with EPI. PMID:22245350
Neural substrates of figurative language during natural speech perception: an fMRI study
Nagels, Arne; Kauschke, Christina; Schrauf, Judith; Whitney, Carin; Straube, Benjamin; Kircher, Tilo
Many figurative expressions are fully conventionalized in everyday speech. Regarding the neural basis of figurative language processing, research has predominantly focused on metaphoric expressions in minimal semantic context. It remains unclear in how far metaphoric expressions during continuous text comprehension activate similar neural networks as isolated metaphors. We therefore investigated the processing of similes (figurative language, e.g., "He smokes like a chimney!") occurring in a short story. Sixteen healthy, male, native German speakers listened to similes that came about naturally in a short story, while blood-oxygenation-level-dependent (BOLD) responses were measured with functional magnetic resonance imaging (fMRI). For the event-related analysis, similes were contrasted with non-figurative control sentences (CS). The stimuli differed with respect to figurativeness, while they were matched for frequency of words, number of syllables, plausibility, and comprehensibility. Similes contrasted with CS resulted in enhanced BOLD responses in the left inferior (IFG) and adjacent middle frontal gyrus. Concrete CS as compared to similes activated the bilateral middle temporal gyri as well as the right precuneus and the left middle frontal gyrus (LMFG). Activation of the left IFG for similes in a short story is consistent with results on single sentence metaphor processing. The findings strengthen the importance of the left inferior frontal region in the processing of abstract figurative speech during continuous, ecologically-valid speech comprehension; the processing of concrete semantic contents goes along with a down-regulation of bilateral temporal regions. PMID:24065897
Compassion, guilt and innocence: An fMRI study of responses to victims who are responsible for their fate.
Fehse, Kai; Silveira, Sarita; Elvers, Katrin; Blautzik, Janusch
Compassion is a human feeling towards an individual who is suffering. However, the responses toward a victim are not always compassionate and may, for example, be moderated by the perceived responsibility of the victim. In the present study, we investigated the neural correlates of compassion and specifically differentiated the responses to other individuals' misfortunes depending on whether the victim was responsible for the event that occurred. In particular, we identified increased activation of the left insula, medial prefrontal cortex (mPFC), and adjacent anterior cingulate cortex when the participants read sentences with innocent compared with responsible victims. The reverse contrast revealed increased activation of the bilateral temporoparietal junction, right precuneus, and right dorsolateral prefrontal cortex (dlPFC). Using a psycho-physiological interaction (PPI) analysis, we demonstrated that in the responsible condition, right dlPFC activation was accompanied by decreased activation in the left insula, anterior cingulate cortex (ACC), and mPFC. This inverse effective connectivity illustrates the antagonism of the dlPFC and mPFC in compassion-related appraisal of external events. More specifically, our results imply that regulatory mechanisms of compassion are related to the perception of responsibility.
Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance
Bakker, Arnold; Albert, Marilyn S.; Krauss, Gregory; Speck, Caroline L.; Gallagher, Michela
individuals with aMCI and therapeutic intervention using fMRI to detect target engagement in response to treatment. PMID:25844322
Quantitative representations of an exaggerated anxiety response in the brain of female spider phobics-a parametric fMRI study.
Zilverstand, Anna; Sorger, Bettina; Kaemingk, Anita; Goebel, Rainer
We employed a novel parametric spider picture set in the context of a parametric fMRI anxiety provocation study, designed to tease apart brain regions involved in threat monitoring from regions representing an exaggerated anxiety response in spider phobics. For the stimulus set, we systematically manipulated perceived proximity of threat by varying a depicted spider's context, size, and posture. All stimuli were validated in a behavioral rating study (phobics n = 20; controls n = 20; all female). An independent group participated in a subsequent fMRI anxiety provocation study (phobics n = 7; controls n = 7; all female), in which we compared a whole-brain categorical to a whole-brain parametric analysis. Results demonstrated that the parametric analysis provided a richer characterization of the functional role of the involved brain networks. In three brain regions-the mid insula, the dorsal anterior cingulate, and the ventrolateral prefrontal cortex-activation was linearly modulated by perceived proximity specifically in the spider phobia group, indicating a quantitative representation of an exaggerated anxiety response. In other regions (e.g., the amygdala), activation was linearly modulated in both groups, suggesting a functional role in threat monitoring. Prefrontal regions, such as dorsolateral prefrontal cortex, were activated during anxiety provocation but did not show a stimulus-dependent linear modulation in either group. The results confirm that brain regions involved in anxiety processing hold a quantitative representation of a pathological anxiety response and more generally suggest that parametric fMRI designs may be a very powerful tool for clinical research in the future, particularly when developing novel brain-based interventions (e.g., neurofeedback training). Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
BOLD-Perfusion Coupling during Monocular and Binocular Stimulation
Gauthier, Claudine; Hoge, Richard D.
Previous studies have suggested that during selective activation of a subset of the zones comprising a columnar system in visual cortex, perfusion increases uniformly in all columns of the system, while increases in oxidative metabolism occur predominantly in the activated columns. This could lead to disproportionately large blood oxygenation level-dependent (BOLD) signal increases for a given flow increase during monocular (relative to binocular) stimulation, due to contributions from columns which undergo large increases in perfusion with little or no change in oxidative metabolism. In the present study, we sought to test this hypothesis by measuring BOLD-perfusion coupling ratios in spatially averaged signals over V1 during monocular and binocular visual stimulation. It was found that, although withholding input to one eye resulted in statistically significant decreases in BOLD and perfusion signals in primary visual cortex, the ratio between BOLD and perfusion increases did not change significantly. These results do not support a gross mismatch between spatial patterns of flow and metabolism response during monocular stimulation. PMID:18350120
No Evidence for Automatic Remapping of Stimulus Features or Location Found with fMRI
Lescroart, Mark D.; Kanwisher, Nancy; Golomb, Julie D.
The input to our visual system shifts every time we move our eyes. To maintain a stable percept of the world, visual representations must be updated with each saccade. Near the time of a saccade, neurons in several visual areas become sensitive to the regions of visual space that their receptive fields occupy after the saccade. This process, known as remapping, transfers information from one set of neurons to another, and may provide a mechanism for visual stability. However, it is not clear whether remapping transfers information about stimulus features in addition to information about stimulus location. To investigate this issue, we recorded blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses while human subjects viewed images of faces and houses (two visual categories with many feature differences). Immediately after some image presentations, subjects made a saccade that moved the previously stimulated location to the opposite side of the visual field. We then used a combination of univariate analyses and multivariate pattern analyses to test whether information about stimulus location and stimulus features were remapped to the ipsilateral hemisphere after the saccades. We found no reliable indication of stimulus feature remapping in any region. However, we also found no reliable indication of stimulus location remapping, despite the fact that our paradigm was highly similar to previous fMRI studies of remapping. The absence of location remapping in our study precludes strong conclusions regarding feature remapping. However, these results also suggest that measurement of location remapping with fMRI depends strongly on the details of the experimental paradigm used. We highlight differences in our approach from the original fMRI studies of remapping, discuss potential reasons for the failure to generalize prior location remapping results, and suggest directions for future research. PMID:27378866
Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance.
Scheeringa, René; Petersson, Karl Magnus; Oostenveld, Robert; Norris, David G; Hagoort, Peter; Bastiaansen, Marcel C M
PET and fMRI experiments have previously shown that several brain regions in the frontal and parietal lobe are involved in working memory maintenance. MEG and EEG experiments have shown parametric increases with load for oscillatory activity in posterior alpha and frontal theta power. In the current study we investigated whether the areas found with fMRI can be associated with these alpha and theta effects by measuring simultaneous EEG and fMRI during a modified Sternberg task This allowed us to correlate EEG at the single trial level with the fMRI BOLD signal by forming a regressor based on single trial alpha and theta power estimates. We observed a right posterior, parametric alpha power increase, which was functionally related to decreases in BOLD in the primary visual cortex and in the posterior part of the right middle temporal gyrus. We relate this finding to the inhibition of neuronal activity that may interfere with WM maintenance. An observed parametric increase in frontal theta power was correlated to a decrease in BOLD in regions that together form the default mode network. We did not observe correlations between oscillatory EEG phenomena and BOLD in the traditional WM areas. In conclusion, the study shows that simultaneous EEG-fMRI recordings can be successfully used to identify the emergence of functional networks in the brain during the execution of a cognitive task.
Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study
Preis, Mira A.; Kröner-Herwig, Birgit; Schmidt-Samoa, Carsten; Dechent, Peter; Barke, Antonia
Background Neuroimaging studies have demonstrated that the actual experience of pain and the perception of another person in pain share common neural substrates, including the bilateral anterior insular cortex and the anterior midcingulate cortex. As many fMRI studies include the exposure of participants to repeated, similar stimuli, we examined whether empathic neural responses were affected by habituation and whether the participants' prior pain experience influenced these habituation effects. Method In 128 trials (four runs), 62 participants (31 women, 23.0 ± 4.2 years) were shown pictures of hands exposed to painful pressure (pain pictures) and unexposed (neutral pictures). After each trial, the participants rated the pain of the model. Prior to the experiment, participants were either exposed to the same pain stimulus (pain exposure group) or not (touch exposure group). In order to assess possible habituation effects, linear changes in the strength of the BOLD response to the pain pictures (relative to the neutral pictures) and in the ratings of the model's pain were evaluated across the four runs. Results Although the ratings of the model's pain remained constant over time, we found neural habituation in the bilateral anterior/midinsular cortex, the posterior midcingulate extending to dorsal posterior cingulate cortex, the supplementary motor area, the cerebellum, the right inferior parietal lobule, and the left superior frontal gyrus, stretching to the pregenual anterior cingulate cortex. The participant's prior pain experience did neither affect their ratings of the model's pain nor their maintenance of BOLD activity in areas associated with empathy. Interestingly, participants with high trait personal distress and fantasy tended to show less habituation in the anterior insula. Conclusion Neural structures showed a decrease of the BOLD signal, indicating habituation over the course of 45 minutes. This can be interpreted as a neuronal mechanism
Plasticity in animal personality traits: does prior experience alter the degree of boldness?
Frost, Ashley J; Winrow-Giffen, Alexandria; Ashley, Paul J; Sneddon, Lynne U
Theoreticians predict that animal 'personality' traits may be maladaptive if fixed throughout different contexts, so the present study aimed to test whether these traits are fixed or plastic. Rainbow trout (Onchorhyncus mykiss) were given emboldening or negative experiences in the forms of watching bold or shy individuals responding to novelty or winning or losing fights to examine whether prior experience affected boldness. Bold individuals that lost fights or watched shy demonstrators became more shy by increasing their latency to approach a novel object, whereas shy observers that watched bold demonstrators remained cautious and did not modify their responses to novelty. Shy winners became bolder and decreased their latency to approach a novel object, but shy losers also displayed this shift. In comparison, control groups showed no change in behaviour. Bold fishes given negative experiences reduced their boldness which may be an adaptive response; however, shy fishes may base their strategic decisions upon self-assessment of their relative competitive ability and increase their boldness in situations where getting to resources more quickly ensures they outcompete better competitors. PMID:17164196
The effect of sleep deprivation on BOLD activity elicited by a divided attention task.
Jackson, Melinda L; Hughes, Matthew E; Croft, Rodney J; Howard, Mark E; Crewther, David; Kennedy, Gerard A; Owens, Katherine; Pierce, Rob J; O'Donoghue, Fergal J; Johnston, Patrick
Sleep loss, widespread in today's society and associated with a number of clinical conditions, has a detrimental effect on a variety of cognitive domains including attention. This study examined the sequelae of sleep deprivation upon BOLD fMRI activation during divided attention. Twelve healthy males completed two randomized sessions; one after 27 h of sleep deprivation and one after a normal night of sleep. During each session, BOLD fMRI was measured while subjects completed a cross-modal divided attention task (visual and auditory). After normal sleep, increased BOLD activation was observed bilaterally in the superior frontal gyrus and the inferior parietal lobe during divided attention performance. Subjects reported feeling significantly more sleepy in the sleep deprivation session, and there was a trend towards poorer divided attention task performance. Sleep deprivation led to a down regulation of activation in the left superior frontal gyrus, possibly reflecting an attenuation of top-down control mechanisms on the attentional system. These findings have implications for understanding the neural correlates of divided attention and the neurofunctional changes that occur in individuals who are sleep deprived.
"Extreme Bold" in the Faculty Ranks
ERIC Educational Resources Information Center
Kuusisto, Stephen
Boldness, defense, and the necessity of talking back remain as central to life with disability in one's time as in Francis Bacon's age. "Therefore all deformed persons are extreme bold," Bacon wrote, "first, as in their own defence, as being exposed to scorn, but in process of time, by a general habit." Perhaps no word carries…
Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation.
Ances, Beau M; Liang, Christine L; Leontiev, Oleg; Perthen, Joanna E; Fleisher, Adam S; Lansing, Amy E; Buxton, Richard B
Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO(2)) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53-years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO(2)) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO(2). For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 +/- 0.07%) compared to the younger group (0.95 +/- 0.14%), despite the finding that the fractional CBF and CMRO(2) changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 +/- 0.4%) than younger subjects (6.5 +/- 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 +/- 4.8 mL/100 mL/min) compared to younger (59.6 +/- 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.
Iterative approach of dual regression with a sparse prior enhances the performance of independent component analysis for group functional magnetic resonance imaging (fMRI) data.
Kim, Yong-Hwan; Kim, Junghoe; Lee, Jong-Hwan
This study proposes an iterative dual-regression (DR) approach with sparse prior regularization to better estimate an individual's neuronal activation using the results of an independent component analysis (ICA) method applied to a temporally concatenated group of functional magnetic resonance imaging (fMRI) data (i.e., Tc-GICA method). An ordinary DR approach estimates the spatial patterns (SPs) of neuronal activation and corresponding time courses (TCs) specific to each individual's fMRI data with two steps involving least-squares (LS) solutions. Our proposed approach employs iterative LS solutions to refine both the individual SPs and TCs with an additional a priori assumption of sparseness in the SPs (i.e., minimally overlapping SPs) based on L(1)-norm minimization. To quantitatively evaluate the performance of this approach, semi-artificial fMRI data were created from resting-state fMRI data with the following considerations: (1) an artificially designed spatial layout of neuronal activation patterns with varying overlap sizes across subjects and (2) a BOLD time series (TS) with variable parameters such as onset time, duration, and maximum BOLD levels. To systematically control the spatial layout variability of neuronal activation patterns across the "subjects" (n=12), the degree of spatial overlap across all subjects was varied from a minimum of 1 voxel (i.e., 0.5-voxel cubic radius) to a maximum of 81 voxels (i.e., 2.5-voxel radius) across the task-related SPs with a size of 100 voxels for both the block-based and event-related task paradigms. In addition, several levels of maximum percentage BOLD intensity (i.e., 0.5, 1.0, 2.0, and 3.0%) were used for each degree of spatial overlap size. From the results, the estimated individual SPs of neuronal activation obtained from the proposed iterative DR approach with a sparse prior showed an enhanced true positive rate and reduced false positive rate compared to the ordinary DR approach. The estimated TCs of the
Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study.
Shi, Yu; Liu, Ziping; Zhang, Shanshan; Li, Qiang; Guo, Shigui; Yang, Jiangming; Wu, Wen
Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP) model and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP) and once during tactile stimulation (SHAM) pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo) values in the pain matrix, limbic system, and default mode network (DMN) and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP.
Influence of Acoustic Overstimulation on the Central Auditory System: An Functional Magnetic Resonance Imaging (fMRI) Study.
Wolak, Tomasz; Cieśla, Katarzyna; Rusiniak, Mateusz; Piłka, Adam; Lewandowska, Monika; Pluta, Agnieszka; Skarżyński, Henryk; Skarżyński, Piotr H
BACKGROUND The goal of the fMRI experiment was to explore the involvement of central auditory structures in pathomechanisms of a behaviorally manifested auditory temporary threshold shift in humans. MATERIAL AND METHODS The material included 18 healthy volunteers with normal hearing. Subjects in the exposure group were presented with 15 min of binaural acoustic overstimulation of narrowband noise (3 kHz central frequency) at 95 dB(A). The control group was not exposed to noise but instead relaxed in silence. Auditory fMRI was performed in 1 session before and 3 sessions after acoustic overstimulation and involved 3.5-4.5 kHz sweeps. RESULTS The outcomes of the study indicate a possible effect of acoustic overstimulation on central processing, with decreased brain responses to auditory stimulation up to 20 min after exposure to noise. The effect can be seen already in the primary auditory cortex. Decreased BOLD signal change can be due to increased excitation thresholds and/or increased spontaneous activity of auditory neurons throughout the auditory system. CONCLUSIONS The trial shows that fMRI can be a valuable tool in acoustic overstimulation studies but has to be used with caution and considered complimentary to audiological measures. Further methodological improvements are needed to distinguish the effects of TTS and neuronal habituation to repetitive stimulation.
Influence of Acoustic Overstimulation on the Central Auditory System: An Functional Magnetic Resonance Imaging (fMRI) Study
Wolak, Tomasz; Cieśla, Katarzyna; Rusiniak, Mateusz; Piłka, Adam; Lewandowska, Monika; Pluta, Agnieszka; Skarżyński, Henryk; Skarżyński, Piotr H.
Background The goal of the fMRI experiment was to explore the involvement of central auditory structures in pathomechanisms of a behaviorally manifested auditory temporary threshold shift in humans. Material/Methods The material included 18 healthy volunteers with normal hearing. Subjects in the exposure group were presented with 15 min of binaural acoustic overstimulation of narrowband noise (3 kHz central frequency) at 95 dB(A). The control group was not exposed to noise but instead relaxed in silence. Auditory fMRI was performed in 1 session before and 3 sessions after acoustic overstimulation and involved 3.5–4.5 kHz sweeps. Results The outcomes of the study indicate a possible effect of acoustic overstimulation on central processing, with decreased brain responses to auditory stimulation up to 20 min after exposure to noise. The effect can be seen already in the primary auditory cortex. Decreased BOLD signal change can be due to increased excitation thresholds and/or increased spontaneous activity of auditory neurons throughout the auditory system. Conclusions The trial shows that fMRI can be a valuable tool in acoustic overstimulation studies but has to be used with caution and considered complimentary to audiological measures. Further methodological improvements are needed to distinguish the effects of TTS and neuronal habituation to repetitive stimulation. PMID:27893698
Task and Resting-State fMRI Reveal Altered Salience Responses to Positive Stimuli in Patients with Major Depressive Disorder
Yang, Yang; Zhong, Ning; Imamura, Kazuyuki; Lu, Shengfu; Li, Mi; Zhou, Haiyan; Li, Huaizhou; Yang, Xiaojing; Wan, Zhijiang; Wang, Gang; Hu, Bin; Li, Kuncheng
Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients' difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses. PMID:27192082
Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome.
Zöller, Daniela; Schaer, Marie; Scariati, Elisa; Padula, Maria Carmela; Eliez, Stephan; Van De Ville, Dimitri
Although often ignored in fMRI studies, moment-to-moment variability of blood oxygenation level dependent (BOLD) signals reveals important information about brain function. Indeed, higher brain signal variability has been associated with better cognitive performance in young adults compared to children and elderly adults. Functional connectivity, a very common approach in resting-state fMRI analysis, is scaled for variance. Thus, alterations might be confounded or driven by BOLD signal variance alterations. Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder that is associated with a vast cognitive and clinical phenotype. To date, several resting-state fMRI studies reported altered functional connectivity in 22q11.2DS, however BOLD signal variance has not yet been analyzed. Here, we employed PLS correlation analysis to reveal multivariate patterns of diagnosis-related alterations and age-relationship throughout the cortex of 50 patients between 9 and 25 years old and 50 healthy controls in the same age range. To address how functional connectivity in the default mode network is influenced by BOLD signal fluctuations, we conducted the same analysis on seed-to-voxel connectivity of the posterior cingulate cortex (PCC) and compared resulting brain patterns. BOLD signal variance was lower mainly in regions of the default mode network and in the dorsolateral prefrontal cortex, but higher in large parts of the temporal lobes. In those regions, BOLD signal variance was correlated with age in healthy controls, but not in patients, suggesting deviant developmental trajectories from child- to adulthood. Positive connectivity of the PCC within the default mode network as well as negative connectivity towards the frontoparietal network were weaker in patients with 22q11.2DS. We furthermore showed that lower functional connectivity of the PCC was not driven by higher BOLD signal variability. Our results confirm the strong implication of BOLD
Restructuring Reward Mechanisms in Nicotine Addiction: A Pilot fMRI Study of Mindfulness-Oriented Recovery Enhancement for Cigarette Smokers
Mathew, A. R.; McConnell, P. A.; Eichberg, C.; Saladin, M. E.; Carpenter, M. J.; Garland, E. L.
The primary goal of this pilot feasibility study was to examine the effects of Mindfulness-Oriented Recovery Enhancement (MORE), a behavioral treatment grounded in dual-process models derived from cognitive science, on frontostriatal reward processes among cigarette smokers. Healthy adult (N = 13; mean (SD) age 49 ± 12.2) smokers provided informed consent to participate in a 10-week study testing MORE versus a comparison group (CG). All participants underwent two fMRI scans: pre-tx and after 8-weeks of MORE. Emotion regulation (ER), smoking cue reactivity (CR), and resting-state functional connectivity (rsFC) were assessed at each fMRI visit; smoking and mood were assessed throughout. As compared to the CG, MORE significantly reduced smoking (d = 2.06) and increased positive affect (d = 2.02). MORE participants evidenced decreased CR-BOLD response in ventral striatum (VS; d = 1.57) and ventral prefrontal cortex (vPFC; d = 1.7) and increased positive ER-BOLD in VS (dVS = 2.13) and vPFC (dvmPFC = 2.66). Importantly, ER was correlated with smoking reduction (r's = .68 to .91) and increased positive affect (r's = .52 to .61). These findings provide preliminary evidence that MORE may facilitate the restructuring of reward processes and play a role in treating the pathophysiology of nicotine addiction. PMID:28373890
[Comparison of reactive EEG changes and fMRI characteristics of brain health based on multivariate statistics].
Sharova, E V; Migalev, A S; Kulikov, M A; Voronov, V G; Boldyreva, G N; Zhavoronkova, L A; Skoriatina, I G; Piashina, D V; Davydova, N Iu; Pronin, I N; Kornienko, V N
To gain a deeper insight into the relationship between the electrogenesis and oxygenation of the brain, fMRI and EEG reactions to identical functional loads (opening of the eyes and right- and left-hand fingering) were compared in 11 young right-handed healthy subjects with statistical techniques. Changes in power, frequency and coherent EEG parameters obtained by 18-channel monopolar recording were compared with values of + BOLD-fMRI response, calculated for 18 corresponding cortical areas on the basis of application of the "virtual cap" by the original algorithm. In reactive changes of both hemodynamic and bioelectrical parameters, sets of independent factors were identified, which were regarded on the basis of their topography as specific (localized in the cortical representation ofa relevant analyzer) and nonspecific (diffuse and similar under different functional loads). Specific component dominated in the fMRI response, whereas non-specific component was characteristic of the EEG reaction. The similar topography of reactive fMRI and EEG factors under normal conditions, confirmed by the correlation analysis, reflects the multilevel character of the systemic organization of the brain activity, visualized, in particular, in the sagittal projections of the individual fMRI images. Each of the reactive EEG factors included all of the EEG quantitative characteristics. EEG coherence, which dominated among other parameters (with a local increase in the cortical representation of a relevant analyzer and a diffuse decrease in the areas of the influence of the regulatory structures) displayed the highest correlation with hemodynamic responses of the brain.
Cluster analysis of resting-state fMRI time series.
Mezer, Aviv; Yovel, Yossi; Pasternak, Ofer; Gorfine, Tali; Assaf, Yaniv
Functional MRI (fMRI) has become one of the leading methods for brain mapping in neuroscience. Recent advances in fMRI analysis were used to define the default state of brain activity, functional connectivity and basal activity. Basal activity measured with fMRI raised tremendous interest among neuroscientists since synchronized brain activity pattern could be retrieved while the subject rests (resting state fMRI). During recent years, a few signal processing schemes have been suggested to analyze the resting state blood oxygenation level dependent (BOLD) signal from simple correlations to spectral decomposition. In most of these analysis schemes, the question asked was which brain areas "behave" in the time domain similarly to a pre-specified ROI. In this work we applied short time frequency analysis and clustering to study the spatial signal characteristics of resting state fMRI time series. Such analysis revealed that clusters of similar BOLD fluctuations are found in the cortex but also in the white matter and sub-cortical gray matter regions (thalamus). We found high similarities between the BOLD clusters and the neuro-anatomical appearance of brain regions. Additional analysis of the BOLD time series revealed a strong correlation between head movements and clustering quality. Experiments performed with T1-weighted time series also provided similar quality of clustering. These observations led us to the conclusion that non-functional contributions to the BOLD time series can also account for symmetric appearance of signal fluctuations. These contributions may include head motions, the underling microvasculature anatomy and cellular morphology.
Brain activation in response to randomized visual stimulation as obtained from conjunction and differential analysis: an fMRI study
NASA Astrophysics Data System (ADS)
Nasaruddin, N. H.; Yusoff, A. N.; Kaur, S.
The objective of this multiple-subjects functional magnetic resonance imaging (fMRI) study was to identify the common brain areas that are activated when viewing black-and-white checkerboard pattern stimuli of various shapes, pattern and size and to investigate specific brain areas that are involved in processing static and moving visual stimuli. Sixteen participants viewed the moving (expanding ring, rotating wedge, flipping hour glass and bowtie and arc quadrant) and static (full checkerboard) stimuli during an fMRI scan. All stimuli have black-and-white checkerboard pattern. Statistical parametric mapping (SPM) was used in generating brain activation. Differential analyses were implemented to separately search for areas involved in processing static and moving stimuli. In general, the stimuli of various shapes, pattern and size activated multiple brain areas mostly in the left hemisphere. The activation in the right middle temporal gyrus (MTG) was found to be significantly higher in processing moving visual stimuli as compared to static stimulus. In contrast, the activation in the left calcarine sulcus and left lingual gyrus were significantly higher for static stimulus as compared to moving stimuli. Visual stimulation of various shapes, pattern and size used in this study indicated left lateralization of activation. The involvement of the right MTG in processing moving visual information was evident from differential analysis, while the left calcarine sulcus and left lingual gyrus are the areas that are involved in the processing of static visual stimulus.
Understanding the dynamic relationship between cerebral blood flow and the BOLD signal: Implications for quantitative functional MRI
Simon, Aaron B.; Buxton, Richard B.
Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool for untangling the physiological processes associated with neural stimulus-induced BOLD activation. However, to date this technique has largely been applied to the study of essentially steady-state physiological changes (baseline to activation) associated with block-design stimuli, and it is unclear whether this approach may be directly extended to the study of more dynamic, naturalistic experimental designs. In this study we tested an assumption underlying this technique whose validity is critical to the application of calibrated BOLD to the study of more dynamic stimuli, that information about fluctuations in venous cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations in CBF, making the independent measurement of CBVv unnecessary. To accomplish this, simultaneous arterial spin labeling and BOLD imaging was used to measure the CBF and BOLD responses to flickering checkerboards with contrasts that oscillated continuously with frequencies of ~0.02-0.16Hz. The measurements were then fit to a dynamic physiological model of the BOLD response in order to explore the range of consistent CMRO2 and CBVv responses. We found that the BOLD and CBF responses were most consistent with relatively tight dynamic coupling between CBF and CMRO2 and a CBVv response that was an order of magnitude slower than either CBF or CMRO2. This finding suggests that the assumption of tight flow-volume coupling may not be strictly valid, complicating the extension of calibrated BOLD to more naturalistic experimental designs. PMID:25862267
Test-Retest Stability of Calibrated BOLD-fMRI in HIV− and HIV+ Subjects
Ances, Beau; Vaida, Florin; Ellis, Ronald; Buxton, Richard
Subject performance, scanner hardware, or biological factors can affect single session neuroimaging measures. Stability studies using calibrated blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) have been performed in health but not disease. We utilized calibrated BOLD-fMRI to determine the effects of HIV on neurovascular coupling. 6 clinically stable HIV-infected patients (HIV+) and 10 seronegative controls (HIV−) were scanned at two separate sessions approximately 3 months apart. Both mild hypercapnia (5% CO2) exposure and a visual functional activation task were performed. Intra-class correlation coefficients (ICC) and inter-subject variance were determined for calibrated BOLD-fMRI measures (baseline cerebral blood flow (CBF), functional CBF, BOLD, and cerebral metabolic rate of oxygen consumption (CMRO2) changes) for HIV+ and HIV− subjects. The two groups did not differ in age, sex, or education. HIV+ subjects had lower mean baseline CBF (p <0.04, Cohen's d=−1.07) and functional BOLD responses (p< 0.001, Cohen's d=−2.47) and a trend towards a decrease in mean functional CBF responses (p= 0.07, Cohen's d=−0.92) despite similar mean functional CMRO2 changes (p= 0.71, Cohen's d=0.19). The stability of each calibrated BOLD-fMRI measure, as assessed by ICC, was significantly lower for HIV+ subjects. In addition, HIV+ participants had greater inter-subject variability for baseline CBF (p <0.02), functional BOLD (p< 0.001), CBF (p< 0.001), and CMRO2 (p< 0.002) responses. Our results demonstrate that calibrated BOLD-fMRI measures have excellent stability within healthy controls. In contrast, these values have greater variability in clinically stable HIV+ subjects and may reflect alterations in coupling between CBF and CMRO2 with disease. PMID:20932922
Simultaneous FMRI and electrophysiology in the rodent brain.
Pan, Wen-ju; Thompson, Garth; Magnuson, Matthew; Majeed, Waqas; Jaeger, Dieter; Keilholz, Shella
To examine the neural basis of the blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) signal, we have developed a rodent model in which functional MRI data and in vivo intracortical recording can be performed simultaneously. The combination of MRI and electrical recording is technically challenging because the electrodes used for recording distort the MRI images and the MRI acquisition induces noise in the electrical recording. To minimize the mutual interference of the two modalities, glass microelectrodes were used rather than metal and a noise removal algorithm was implemented for the electrophysiology data. In our studies, two microelectrodes were separately implanted in bilateral primary somatosensory cortices (SI) of the rat and fixed in place. One coronal slice covering the electrode tips was selected for functional MRI. Electrode shafts and fixation positions were not included in the image slice to avoid imaging artifacts. The removed scalp was replaced with toothpaste to reduce susceptibility mismatch and prevent Gibbs ringing artifacts in the images. The artifact structure induced in the electrical recordings by the rapidly-switching magnetic fields during image acquisition was characterized by averaging all cycles of scans for each run. The noise structure during imaging was then subtracted from original recordings. The denoised time courses were then used for further analysis in combination with the fMRI data. As an example, the simultaneous acquisition was used to determine the relationship between spontaneous fMRI BOLD signals and band-limited intracortical electrical activity. Simultaneous fMRI and electrophysiological recording in the rodent will provide a platform for many exciting applications in neuroscience in addition to elucidating the relationship between the fMRI BOLD signal and neuronal activity.
Quantum theory with bold operator tensors.
Hardy, Lucien
In this paper, we present a formulation of quantum theory in terms of bold operator tensors. A circuit is built up of operations where an operation corresponds to a use of an apparatus. We associate collections of operator tensors (which together comprise a bold operator) with these apparatus uses. We give rules for combining bold operator tensors such that, for a circuit, they give a probability distribution over the possible outcomes. If we impose certain physicality constraints on the bold operator tensors, then we get exactly the quantum formalism. We provide both symbolic and diagrammatic ways to represent these calculations. This approach is manifestly covariant in that it does not require us to foliate the circuit into time steps and then evolve a state. Thus, the approach forms a natural starting point for an operational approach to quantum field theory.
Cortical connective field estimates from resting state fMRI activity.
Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V; Dumoulin, Serge O; Renken, Remco; Curčić-Blake, Branislava; Cornelissen, Frans W
One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that-despite some variability in CF estimates between RS scans-neural properties such as CF maps and CF size can be derived from resting state data.
Cortical connective field estimates from resting state fMRI activity
Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V.; Dumoulin, Serge O.; Renken, Remco; Ćurčić-Blake, Branislava; Cornelissen, Frans W.
One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that—despite some variability in CF estimates between RS scans—neural properties such as CF maps and CF size can be derived from resting state data. PMID:25400541
Non-extensive entropy and the extraction of BOLD spatial information in event-related functional MRI
NASA Astrophysics Data System (ADS)
Sturzbecher, M. J.; Tedeschi, W.; Cabella, B. C. T.; Baffa, O.; Neves, U. P. C.; de Araujo, D. B.
Functional magnetic resonance imaging (fMRI) data analysis has been carried out recently in the framework of information theory, by means of the Shannon entropy. As a natural extension, a method based on the generalized Tsallis entropy was developed to the analysis event-related (ER-fMRI), where a brief stimulus is presented, followed by a long period of rest. The new technique aims for spatial localization neuronal activity due to a specific task. This method does not require a priori hypothesis of the hemodynamic response function (HRF) shape and the linear relation between BOLD responses with the presented task. Numerical simulations were performed so as to determine the optimal values of the Tsallis q parameter and the number of levels, L. In order to avoid undesirable divergences of the Tsallis entropy, only positive q values were studied. Results from simulated data (with L = 3) indicated that, for q = 0.8, the active brain areas are detected with the highest performance. Moreover, the method was tested for an in vivo experiment and demonstrated the ability to discriminate active brain regions that selectively responded to a bilateral motor task.
Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal
Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo
Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow. PMID:19636388
Response to {open_quotes}Comment on {open_quote}Reversible work of formation of an embryo of a new phase within a uniform macroscopic mother phase{close_quote}thinsp{close_quotes} [J. Chem. Phys. {bold 111}, 3769 (1999)
Debenedetti, P.G.; Reiss, H.
External constraints are necessary in order to calculate the energetics of embryo formation when the embryo is not a critical nucleus. The expression for the reversible work of formation obtained in by Debenedetti and Reiss [J. Chem. Phys. {bold 108}, 5498 (1998)] is rigorous and valid regardless of the relative densities of the embryo and mother phase. {copyright} {ital 1999 American Institute of Physics.}
Spatial Mnemonic Encoding: Theta Power Decreases and Medial Temporal Lobe BOLD Increases Co-Occur during the Usage of the Method of Loci
Volberg, Gregor; Goldhacker, Markus; Hanslmayr, Simon
Abstract The method of loci is one, if not the most, efficient mnemonic encoding strategy. This spatial mnemonic combines the core cognitive processes commonly linked to medial temporal lobe (MTL) activity: spatial and associative memory processes. During such processes, fMRI studies consistently demonstrate MTL activity, while electrophysiological studies have emphasized the important role of theta oscillations (3–8 Hz) in the MTL. However, it is still unknown whether increases or decreases in theta power co-occur with increased BOLD signal in the MTL during memory encoding. To investigate this question, we recorded EEG and fMRI separately, while human participants used the spatial method of loci or the pegword method, a similarly associative but nonspatial mnemonic. The more effective spatial mnemonic induced a pronounced theta power decrease source localized to the left MTL compared with the nonspatial associative mnemonic strategy. This effect was mirrored by BOLD signal increases in the MTL. Successful encoding, irrespective of the strategy used, elicited decreases in left temporal theta power and increases in MTL BOLD activity. This pattern of results suggests a negative relationship between theta power and BOLD signal changes in the MTL during memory encoding and spatial processing. The findings extend the well known negative relation of alpha/beta oscillations and BOLD signals in the cortex to theta oscillations in the MTL. PMID:28101523
Spatial Mnemonic Encoding: Theta Power Decreases and Medial Temporal Lobe BOLD Increases Co-Occur during the Usage of the Method of Loci.
Fellner, Marie-Christin; Volberg, Gregor; Wimber, Maria; Goldhacker, Markus; Greenlee, Mark W; Hanslmayr, Simon
The method of loci is one, if not the most, efficient mnemonic encoding strategy. This spatial mnemonic combines the core cognitive processes commonly linked to medial temporal lobe (MTL) activity: spatial and associative memory processes. During such processes, fMRI studies consistently demonstrate MTL activity, while electrophysiological studies have emphasized the important role of theta oscillations (3-8 Hz) in the MTL. However, it is still unknown whether increases or decreases in theta power co-occur with increased BOLD signal in the MTL during memory encoding. To investigate this question, we recorded EEG and fMRI separately, while human participants used the spatial method of loci or the pegword method, a similarly associative but nonspatial mnemonic. The more effective spatial mnemonic induced a pronounced theta power decrease source localized to the left MTL compared with the nonspatial associative mnemonic strategy. This effect was mirrored by BOLD signal increases in the MTL. Successful encoding, irrespective of the strategy used, elicited decreases in left temporal theta power and increases in MTL BOLD activity. This pattern of results suggests a negative relationship between theta power and BOLD signal changes in the MTL during memory encoding and spatial processing. The findings extend the well known negative relation of alpha/beta oscillations and BOLD signals in the cortex to theta oscillations in the MTL.
Material-dependent and material-independent selection processes in the frontal and parietal lobes: an event-related fMRI investigation of response competition
NASA Technical Reports Server (NTRS)
Hazeltine, Eliot; Bunge, Silvia A.; Scanlon, Michael D.; Gabrieli, John D E.
The present study used the flanker task [Percept. Psychophys. 16 (1974) 143] to identify neural structures that support response selection processes, and to determine which of these structures respond differently depending on the type of stimulus material associated with the response. Participants performed two versions of the flanker task while undergoing event-related functional magnetic resonance imaging (fMRI). Both versions of the task required participants to respond to a central stimulus regardless of the responses associated with simultaneously presented flanking stimuli, but one used colored circle stimuli and the other used letter stimuli. Competition-related activation was identified by comparing Incongruent trials, in which the flanker stimuli indicated a different response than the central stimulus, to Neutral stimuli, in which the flanker stimuli indicated no response. A region within the right inferior frontal gyrus exhibited significantly more competition-related activation for the color stimuli, whereas regions within the middle frontal gyri of both hemispheres exhibited more competition-related activation for the letter stimuli. The border of the right middle frontal and inferior frontal gyri and the anterior cingulate cortex (ACC) were significantly activated by competition for both types of stimulus materials. Posterior foci demonstrated a similar pattern: left inferior parietal cortex showed greater competition-related activation for the letters, whereas right parietal cortex was significantly activated by competition for both materials. These findings indicate that the resolution of response competition invokes both material-dependent and material-independent processes.
BOLD fractional contribution to resting-state functional connectivity above 0.1 Hz
Chen, Jingyuan; Glover, Gary H.
Blood oxygen level dependent (BOLD) spontaneous signals from resting-state (RS) brains have typically been characterized by low-pass filtered timeseries at frequencies ≤ 0.1 Hz, and studies of these low-frequency fluctuations have contributed exceptional understanding of the baseline functions of our brain. Very recently, emerging evidence has demonstrated that spontaneous activities may persist in higher frequency bands (even up to 0.8 Hz), while presenting less variable network patterns across the scan duration. However, as an indirect measure of neuronal activity, BOLD signal results from an inherently slow hemodynamic process, which in fact might be too slow to accommodate the observed high-frequency functional connectivity (FC). To examine whether the observed high-frequency spontaneous FC originates from BOLD contrast, we collected RS data as a function of echo time (TE). Here we focus on two specific resting state networks – the default-mode network (DMN) and executive control network (ECN), and the major findings are fourfold: (1) we observed BOLD-like linear TE-dependence in the spontaneous activity at frequency bands up to 0.5 Hz (the maximum frequency that can be resolved with TR = 1s), supporting neural relevance of the RSFC at higher frequency range; (2) Conventional models of hemodynamic response functions must be modified to support resting state BOLD contrast, especially at higher frequencies; (3) there are increased fractions of non-BOLD-like contributions to the RSFC above the conventional 0.1 Hz (non-BOLD/BOLD contrast at 0.4~0.5 Hz is ~ 4 times that at <0.1 Hz); and (4) the spatial patterns of RSFC are frequency-dependent. Possible mechanisms underlying the present findings and technical concerns regarding RSFC above 0.1 Hz are discussed. PMID:25497686
Implications of cortical balanced excitation and inhibition, functional heterogeneity, and sparseness of neuronal activity in fMRI
Xu, Jiansong
Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies often report inconsistent findings, probably due to brain properties such as balanced excitation and inhibition and functional heterogeneity. These properties indicate that different neurons in the same voxels may show variable activities including concurrent activation and deactivation, that the relationships between BOLD signal and neural activity (i.e., neurovascular coupling) are complex, and that increased BOLD signal may reflect reduced deactivation, increased activation, or both. The traditional general-linear-model-based-analysis (GLM-BA) is a univariate approach, cannot separate different components of BOLD signal mixtures from the same voxels, and may contribute to inconsistent findings of fMRI. Spatial independent component analysis (sICA) is a multivariate approach, can separate the BOLD signal mixture from each voxel into different source signals and measure each separately, and thus may reconcile previous conflicting findings generated by GLM-BA. We propose that methods capable of separating mixed signals such as sICA should be regularly used for more accurately and completely extracting information embedded in fMRI datasets. PMID:26341939
The contribution of different frequency bands of fMRI data to the correlation with EEG alpha rhythm.
Zhan, Zhichao; Xu, Lele; Zuo, Tian; Xie, Dongliang; Zhang, Jiacai; Yao, Li; Wu, Xia
Alpha rhythm is a prominent EEG rhythm observed during resting state and is thought to be related to multiple cognitive processes. Previous simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) studies have demonstrated that alpha rhythm is associated with blood oxygen level dependent (BOLD) signals in several different functional networks. How these networks influence alpha rhythm respectively is unclear. The low-frequency oscillations (LFO) in spontaneous BOLD activity are thought to contribute to the local correlations in resting state. Recent studies suggested that either LFO or other components of fMRI can be further divided into sub-components on different frequency bands. We hypothesized that those BOLD sub-components characterized the contributions of different brain networks to alpha rhythm. To test this hypothesis, EEG and fMRI data were simultaneously recorded from 17 human subjects performing an eyes-close resting state experiment. EEG alpha rhythm was correlated with the filtered fMRI time courses at different frequency bands (0.01-0.08 Hz, 0.08-0.25 Hz, 0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198-0.25 Hz). The results demonstrated significant relations between alpha rhythm and the BOLD signals in the visual network and in the attention network at LFO band, especially at the very low frequency band (0.01-0.027 Hz).
Neural Responses to Visual Food Stimuli After a Normal vs. Higher Protein Breakfast in Breakfast-Skipping Teens: A Pilot fMRI Study
Leidy, Heather J.; Lepping, Rebecca J.; Savage, Cary R.; Harris, Corey T.
This functional magnetic resonance imaging (fMRI) pilot study identified whether breakfast consumption would alter the neural activity in brain regions associated with food motivation and reward in overweight "breakfast skipping" (BS) adolescent girls and examined whether increased protein at breakfast would lead to additional alterations. Ten girls (Age: 15 ± 1 years; BMI percentile 93 ± 1%; BS 5 ± 1×/week) completed 3 testing days. Following the BS day, the participants were provided with, in randomized order, normal protein (NP; 18 ± 1 g protein) or higher protein (HP; 50 ± 1 g protein) breakfast meals to consume at home for 6 days. On day 7 of each pattern, the participants came to the laboratory to consume their respective breakfast followed by appetite questionnaires and an fMRI brain scan to identify brain activation responses to viewing food vs. nonfood images prior to lunch. Breakfast consumption led to enduring (i.e., 3-h post breakfast) reductions in neural activation in the hippocampus, amygdala, cingulate, and parahippocampus vs. BS. HP led to enduring reductions in insula and middle prefrontal cortex activation vs. NP. Hippocampal, amygdala, cingulate, and insular activations were correlated with appetite and inversely correlated with satiety. In summary, the addition of breakfast led to alterations in brain activation in regions previously associated with food motivation and reward with additional alterations following the higher-protein breakfast. These data suggest that increased dietary protein at breakfast might be a beneficial strategy to reduce reward-driven eating behavior in overweight teen girls. Due to the small sample size, caution is warranted when interpreting these preliminary findings. PMID:21546927
Alteration of brain functional network at rest and in response to YMCA physical stress test in concussed athletes: RsFMRI study.
Slobounov, S M; Gay, M; Zhang, K; Johnson, B; Pennell, D; Sebastianelli, W; Horovitz, S; Hallett, M
There is still controversy in the literature whether a single episode of mild traumatic brain injury (mTBI) results in short- and/or long-term functional and structural deficits in the concussed brain. With the inability of traditional brain imaging techniques to properly assess the severity of brain damage induced by a concussive blow, there is hope that more advanced applications such as resting state functional magnetic resonance imaging (rsFMRI) will be more specific in accurately diagnosing mTBI. In this rsFMRI study, we examined 17 subjects 10±2 days post-sports-related mTBI and 17 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the resting state brain network is disrupted following a single concussive blow. We hypothesized that advanced brain imaging techniques may reveal subtle alterations of functional brain connections in asymptomatic mTBI subjects. There are several findings of interest. All mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. The mTBI subjects revealed a disrupted functional network both at rest and in response to the YMCA physical stress test. Specifically, interhemispheric connectivity was significantly reduced in the primary visual cortex, hippocampal and dorsolateral prefrontal cortex networks (p<0.05). The YMCA physical stress induced nonspecific and similar changes in brain network connectivity patterns in both the mTBI and NV groups. These major findings are discussed in relation to underlying mechanisms, clinical assessment of mTBI, and current debate regarding functional brain connectivity in a clinical population. Overall, our major findings clearly indicate that functional brain alterations in the acute phase of injury are overlooked when conventional clinical and neuropsychological examinations are used.
Brain responses to erotic and other emotional stimuli in breast cancer survivors with and without distress about low sexual desire: a preliminary fMRI study.
Versace, Francesco; Engelmann, Jeffrey M; Jackson, Edward F; Slapin, Aurelija; Cortese, Kristin M; Bevers, Therese B; Schover, Leslie R
Many breast cancer survivors report a loss of sexual desire and arousability, consonant with the new DSM-V category of female sexual interest/arousal disorder. The cause of decreased sexual desire and pleasure after treatment for cancer is unknown. One possibility is that cancer, or treatment for cancer, damages brain circuits that are involved in reward-seeking. To test the hypothesis that brain reward systems are involved in decreased sexual desire in breast cancer survivors, we used functional magnetic resonance imaging (fMRI) to compare brain responses to erotica and other emotional stimuli in two groups of women previously treated for breast cancer with chemotherapy: those who were distressed about a perceived loss of sexual desire and those who may have had low desire, but were not distressed about it. Women distressed about their desire had reduced brain responses to erotica in the anterior cingulate and dorsolateral prefrontal cortex, which are part of the brain reward system. This study is the first to demonstrate, in cancer survivors, that problems with sexual desire/arousability are associated with blunted brain responses to erotica in reward systems. Future research is necessary to determine whether brain responses differ as a result of chemotherapy, hormone therapy, and menopausal status. This may contribute to the development of new, evidence-based interventions for one of the most prevalent and enduring side effects of cancer treatment.
Neural responses to witnessing peer rejection after being socially excluded: fMRI as a window into adolescents' emotional processing
Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Dapretto, Mirella
During adolescence, concerns about peer rejection and acceptance become increasingly common. Adolescents regularly experience peer rejection firsthand and witness these behaviors among their peers. In the current study, neuroimaging techniques were employed to conduct a preliminary investigation of the affective and cognitive processes involved in witnessing peer acceptance and rejection—specifically when these witnessed events occur in the immediate aftermath of a firsthand experience with rejection. During an fMRI scan, twenty-three adolescents underwent a simulated experience of firsthand peer rejection. Then, immediately following this experience they watched as another adolescent was ostensibly first accepted and then rejected. Findings indicated that in the immediate aftermath of being rejected by peers, adolescents displayed neural activity consistent with distress when they saw another peer being accepted, and neural activity consistent with emotion regulation and mentalizing (e.g., perspective-taking) processes when they saw another peer being rejected. Furthermore, individuals displaying a heightened sensitivity to firsthand rejection were more likely to show neural activity consistent with distress when observing a peer being accepted. Findings are discussed in terms of how witnessing others being accepted or rejected relates to adolescents' interpretations of both firsthand and observed experiences with peers. Additionally, the potential impact that witnessed events might have on the broader perpetuation of bullying at this age is also considered. PMID:24033579
Is dorsal anterior cingulate cortex activation in response to social exclusion due to expectancy violation? An fMRI study
Kawamoto, Taishi; Onoda, Keiichi; Nakashima, Ken'ichiro; Nittono, Hiroshi; Yamaguchi, Shuhei; Ura, Mitsuhiro
People are typically quite sensitive about being accepted or excluded by others. Previous studies have suggested that the dorsal anterior cingulate cortex (dACC) is a key brain region involved in the detection of social exclusion. However, this region has also been shown to be sensitive to non-social expectancy violations. We often expect other people to follow an unwritten rule in which they include us as they would expect to be included, such that social exclusion likely involves some degree of expectancy violation. The present event-related functional magnetic resonance imaging (fMRI) study sought to separate the effects of expectancy violation from those of social exclusion, such that we employed an "overinclusion" condition in which a player was unexpectedly overincluded in the game by the other players. With this modification, we found that the dACC and right ventrolateral prefrontal cortex (rVLPFC) were activated by exclusion, relative to overinclusion. In addition, we identified a negative correlation between exclusion-evoked brain activity and self-rated social pain in the rVLPFC, but not in the dACC. These findings suggest that the rVLPFC is critical for regulating social pain, whereas the dACC plays an important role in the detection of exclusion. The neurobiological basis of social exclusion is different from that of mere expectancy violation. PMID:22866035
Coupling between pupil fluctuations and resting-state fMRI uncovers a slow build-up of antagonistic responses in the human cortex.
Yellin, Dov; Berkovich-Ohana, Aviva; Malach, Rafael
Even in absence of overt tasks, the human cortex manifests rich patterns of spontaneous "resting state" BOLD-fMRI fluctuations. However, the link of these spontaneous fluctuations to behavior is presently unclear. Attempts to directly investigate this link invariably lead to disruptions of the resting state. Here we took advantage of the well-established association between pupil diameter and attentional gain to address this issue by examining the correlation between the resting state BOLD and pupil fluctuations. Our results uncover a spontaneously emerging spatiotemporal pupil-BOLD correlation whereby a slow buildup of activity in default mode areas preceded both pupil dilation and wide-spread BOLD suppression in sensorimotor cortex. Control experiments excluded a role for luminance fluctuations or fixation. Comparing the pupil-correlated patterns to activation maps during visual imagery revealed a substantial overlap. Our results indicate a link between behavior, as indexed by pupil diameter, and resting state BOLD fluctuations. These pupil dilations, assumed to be related to attentional gain, were associated with spontaneously emerging antagonism between fundamental cortical networks.
Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis.
Takemura, Yoshinori; Yamashita, Akira; Horiuchi, Hiroshi; Furuya, Masaharu; Yanase, Makoto; Niikura, Keiichi; Imai, Satoshi; Hatakeyama, Noboru; Kinoshita, Hiroyuki; Tsukiyama, Yoshi; Senba, Emiko; Matoba, Motohiro; Kuzumaki, Naoko; Yamazaki, Mitsuaki; Suzuki, Tsutomu; Narita, Minoru
Neuropathic pain is the most difficult pain to manage in the pain clinic, and sleep problems are common among patients with chronic pain including neuropathic pain. In the present study, we tried to visualize the intensity of pain by assessing neuronal activity and investigated sleep disturbance under a neuropathic pain-like state in mice using functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)/electromyogram (EMG), respectively. Furthermore, we investigated the effect of gabapentin (GBP) on these phenomena. In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, fMRI showed that sciatic nerve ligation produced a significant increase in the blood oxygenation level-dependent (BOLD) signal intensity in the pain matrix, which was significantly decreased 2 h after the i.p. injection of GBP. Based on the results of an EEG/EMG analysis, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase, and the sleep disturbance was almost completely alleviated by a higher dose of GBP in nerve-ligated mice. These findings suggest that neuropathic pain associated with sleep disturbance can be objectively assessed by fMRI and EEG/EMG analysis in animal models. Furthermore, GBP may improve the quality of sleep as well as control pain in patients with neuropathic pain.
Multimodal description of whole brain connectivity: A comparison of resting state MEG, fMRI, and DWI
Garcés, Pilar; Pereda, Ernesto; Hernández‐Tamames, Juan A.; Del‐Pozo, Francisco; Maestú, Fernando
Abstract Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion‐weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood‐oxygenation level‐dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI‐FC, and MEG‐FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI‐FC, and MEG‐FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI‐FC; SC and MEG‐FC at theta, alpha, beta and gamma bands; and fMRI‐FC and MEG‐FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance. Hum Brain Mapp 37:20–34, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26503502
Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism.
Krach, Sören; Kamp-Becker, Inge; Einhäuser, Wolfgang; Sommer, Jens; Frässle, Stefan; Jansen, Andreas; Rademacher, Lena; Müller-Pinzler, Laura; Gazzola, Valeria; Paulus, Frieder M
Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life.
Response inhibition failure to visual stimuli paired with a "single-type" stressor in PTSD patients: an fMRI pilot study.
Brunetti, Marcella; Sepede, Gianna; Ferretti, Antonio; Mingoia, Gianluca; Romani, Gian Luca; Babiloni, Claudio
Patients with post-traumatic stress disorder (PTSD) tend to misinterpret innocuous stimuli as potential threats, possibly due to a conditioning provoked by traumatic episodes. Previous neuroimaging evidence has shown an abnormal activation of the amygdala and prefrontal cortex in PTSD patients during fear conditioning and extinction. Nevertheless, the effects of a single-type adverse stressor on that circuit remain poorly explored. We tested the hypothesis that a single-type adverse episode is able to affect the prefrontal cortex and amygdala response to conditioned stimuli. To test this hypothesis, fMRI recordings were performed in PTSD patients and trauma-exposed controls during the observation of neutral and negative paired or non-paired pictures with an adverse stimulus by means of a single association. Results showed that left amygdala activation during negative reinforced stimuli was correlated with the score of PTSD clinical scale across all subjects. Furthermore, in the traumatized non-PTSD group, the activation of the dorso-medial prefrontal cortex and bilateral amygdala was lower during the observation of the reinforced (CS(+)) versus non-reinforced pictures (CS(-)) in response to emotionally negative stimuli. This was not the case in the PTSD patients. These results suggest that in PTSD patients, a single-episode conditioning unveils the failure of an inhibitory mechanism moderating the activity of the prefrontal cortex and amygdala in response to adverse and neutral stimuli.
Differences in aggression, activity and boldness between native and introduced populations of an invasive crayfish
Pintor, L.M.; Sih, A.; Bauer, M.L.
Aggressiveness, along with foraging voracity and boldness, are key behavioral mechanisms underlying the competitive displacement and invasion success of exotic species. However, do aggressiveness, voracity and boldness of the invader depend on the presence of an ecologically similar native competitor in the invaded community? We conducted four behavioral assays to compare aggression, foraging voracity, threat response and boldness to forage under predation risk of multiple populations of exotic signal crayfish Pacifastacus leniusculus across its native and invaded range with and without a native congener, the Shasta crayfish P. fortis. We predicted that signal crayfish from the invaded range and sympatric with a native congener (IRS) should be more aggressive to outcompete a close competitor than populations from the native range (NR) or invaded range and allopatric to a native congener (IRA). Furthermore, we predicted that IRS populations of signal crayfish should be more voracious, but less bold to forage under predation risk since native predators and prey likely possess appropriate behavioral responses to the invader. Contrary to our predictions, results indicated that IRA signal crayfish were more aggressive towards conspecifics and more voracious and active foragers, yet also bolder to forage under predation risk in comparison to NR and IRS populations, which did not differ in behavior. Higher aggression/voracity/ boldness was positively correlated with prey consumption rates, and hence potential impacts on prey. We suggest that the positive correlations between aggression/voracity/boldness are the result of an overall aggression syndrome. Results of stream surveys indicated that IRA streams have significantly lower prey biomass than in IRS streams, which may drive invading signal crayfish to be more aggressive/voracious/bold to acquire resources to establish a population. ?? 2008 The Authors.
The Effect of Task-Irrelevant Fearful-Face Distractor on Working Memory Processing in Mild Cognitive Impairment versus Healthy Controls: An Exploratory fMRI Study in Female Participants
Burhan, Amer M.; Anazodo, Udunna C.; Chung, Jun Ku; Arena, Amanda; Graff-Guerrero, Ariel; Mitchell, Derek G. V.
In mild cognitive impairment (MCI), a risk state for Alzheimer's disease, patients have objective cognitive deficits with relatively preserved functioning. fMRI studies have identified anomalies during working memory (WM) processing in individuals with MCI. The effect of task-irrelevant emotional face distractor on WM processing in MCI remains unclear. We aim to explore the impact of fearful-face task-irrelevant distractor on WM processing in MCI using fMRI. Hypothesis. Compared to healthy controls (HC), MCI patients will show significantly higher BOLD signal in a priori identified regions of interest (ROIs) during a WM task with a task-irrelevant emotional face distractor. Methods. 9 right-handed female participants with MCI and 12 matched HC performed a WM task with standardized task-irrelevant fearful versus neutral face distractors randomized and counterbalanced across WM trials. MRI images were acquired during the WM task and BOLD signal was analyzed using statistical parametric mapping (SPM) to identify signal patterns during the task response phase. Results. Task-irrelevant fearful-face distractor resulted in higher activation in the amygdala, anterior cingulate, and frontal areas, in MCI participants compared to HC. Conclusions. This exploratory study suggests altered WM processing as a result of fearful-face distractor in MCI. PMID:26949290
Selectively reduced responses to smoking cues in amygdala following extinction-based smoking cessation: results of a preliminary functional magnetic resonance imaging study.
McClernon, F Joseph; Hiott, F Berry; Liu, Jim; Salley, Alfred N; Behm, Frederique M; Rose, Jed E
Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment. The aims of this study was to evaluate the effect of an extinction-based smoking cessation treatment on brain responses to smoking cues using blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Sixteen (n = 16) dependent smokers were scanned using BOLD fMRI at baseline, following 2-4 weeks of smoking RNC cigarettes while wearing a 21-mg nicotine patch, and 2-4 weeks following quitting smoking. During scanning, participants viewed smoking-related pictures (e.g. lit cigarette) and pictures of people engaged in everyday activities (e.g. using a stapler). Event-related BOLD responses to smoking and control cues were analyzed in regions of interest (ROIs) known to subserve reward, attention, motivation and emotion. The extinction-based treatment simultaneously attenuated responses to smoking cues in amygdala while potentiating responses to control cues. Exploratory analysis indicated that this pattern was also observed in the thalamus of future abstinent but not relapsing smokers. The results of this preliminary study suggest that an extinction-based treatment for smoking cessation alters brain responses to smoking and control cues in amygdala--a region previously associated with drug cue reactivity and extinction.
BOLD subjective value signals exhibit robust range adaptation.
Cox, Karin M; Kable, Joseph W
Many theories of decision making assume that choice options are assessed along a common subjective value (SV) scale. The neural correlates of SV are widespread and reliable, despite the wide variation in the range of values over which decisions are made (e.g., between goods worth a few dollars, in some cases, or hundreds of dollars, in others). According to adaptive coding theories (Barlow, 1961), an efficient value signal should exhibit range adaptation, such that neural activity maintains a fixed dynamic range, and the slope of the value response varies inversely with the range of values within the local context. Although monkey data have demonstrated range adaptation in single-unit correlates of value (Padoa-Schioppa, 2009; Kobayashi et al., 2010), whether BOLD value signals exhibit similar range adaptation is unknown. To test for this possibility, we presented human participants with choices between a fixed immediate and variable delayed payment options. Across two conditions, the delayed options' SVs spanned either a narrow or wide range. SV-tracking activity emerged in the posterior cingulate, ventral striatum, anterior cingulate, and ventromedial prefrontal cortex. Throughout this network, we observed evidence consistent with the predictions of range adaptation: the SV response slope increased in the narrow versus wide range, with statistically significant slope changes confirmed for the posterior cingulate and ventral striatum. No regions exhibited a reliably increased BOLD activity range in the wide versus narrow condition. Our observations of range adaptation present implications for the interpretation of BOLD SV responses that are measured across different contexts or individuals.
BOLD and its connection to dopamine release in human striatum: a cross-cohort comparison
Lohrenz, Terry; Kishida, Kenneth T.
Activity in midbrain dopamine neurons modulates the release of dopamine in terminal structures including the striatum, and controls reward-dependent valuation and choice. This fluctuating release of dopamine is thought to encode reward prediction error (RPE) signals and other value-related information crucial to decision-making, and such models have been used to track prediction error signals in the striatum as encoded by BOLD signals. However, until recently there have been no comparisons of BOLD responses and dopamine responses except for one clear correlation of these two signals in rodents. No such comparisons have been made in humans. Here, we report on the connection between the RPE-related BOLD signal recorded in one group of subjects carrying out an investment task, and the corresponding dopamine signal recorded directly using fast-scan cyclic voltammetry in a separate group of Parkinson's disease patients undergoing DBS surgery while performing the same task. The data display some correspondence between the signal types; however, there is not a one-to-one relationship. Further work is necessary to quantify the relationship between dopamine release, the BOLD signal and the computational models that have guided our understanding of both at the level of the striatum. This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574306
Using fMRI to decode true thoughts independent of intention to conceal.
Yang, Zhi; Huang, Zirui; Gonzalez-Castillo, Javier; Dai, Rui; Northoff, Georg; Bandettini, Peter
Multi-variate pattern analysis (MVPA) applied to BOLD-fMRI has proven successful at decoding complicated fMRI signal patterns associated with a variety of cognitive processes. One cognitive process, not yet investigated, is the mental representation of "Yes/No" thoughts that precede the actual overt response to a binary "Yes/No" question. In this study, we focus on examining: (1) whether spatial patterns of the hemodynamic response carry sufficient information to allow reliable decoding of "Yes/No" thoughts; and (2) whether decoding of "Yes/No" thoughts is independent of the intention to respond honestly or dishonestly. To achieve this goal, we conducted two separate experiments. Experiment 1, collected on a 3T scanner, examined the whole brain to identify regions that carry sufficient information to permit significantly above-chance prediction of "Yes/No" thoughts at the group level. In Experiment 2, collected on a 7T scanner, we focused on the regions identified in Experiment 1 to examine the capability of achieving high decoding accuracy at the single subject level. A set of regions--namely right superior temporal gyrus, left supra-marginal gyrus, and left middle frontal gyrus--exhibited high decoding power. Decoding accuracy for these regions increased with trial averaging. When 18 trials were averaged, the median accuracies were 82.5%, 77.5%, and 79.5%, respectively. When trials were separated according to deceptive intentions (set via experimental cues), and classifiers were trained on honest trials, but tested on trials where subjects were asked to deceive, the median accuracies of these regions still reached 66%, 75%, and 78.5%. These results provide evidence that concealed "Yes/No" thoughts are encoded in the BOLD signal, retaining some level of independence from the subject's intentions to answer honestly or dishonestly. These findings also suggest the theoretical possibility for more efficient brain-computer interfaces where subjects only need to think
Chronotype Modulates Language Processing-Related Cerebral Activity during Functional MRI (fMRI)
Warbrick, Tracy; Shah, N. J.
Objective Based on individual daily physiological cycles, humans can be classified as early (EC), late (LC) and intermediate (IC) chronotypes. Recent studies have verified that chronotype-specificity relates to performance on cognitive tasks: participants perform more efficiently when tested in the chronotype-specific optimal time of day than when tested in their non-optimal time. Surprisingly, imaging studies focussing on the underlying neural mechanisms of potential chronotype-specificities are sparse. Moreover, chronotype-specific alterations of language-related semantic processing have been neglected so far. Methods 16 male, healthy ECs, 16 ICs and 16 LCs participated in a fast event-related functional Magnetic Resonance Imaging (fMRI) paradigm probing semantic priming. Subjects read two subsequently presented words (prime, target) and were requested to determine whether the target word was an existing word or a non-word. Subjects were tested during their individual evening hours when homeostatic sleep pressure and circadian alertness levels are high to ensure equal entrainment. Results Chronotype-specificity is associated with task-performance and brain activation. First, ECs exhibited slower reaction times than LCs. Second, ECs showed attenuated BOLD responses in several language-related brain areas, e.g. in the left postcentral gyrus, left and right precentral gyrus and in the right superior frontal gyrus. Additionally, increased BOLD responses were revealed for LCs as compared to ICs in task-related areas, e.g. in the right inferior parietal lobule and in the right postcentral gyrus. Conclusions These findings reveal that even basic language processes are associated with chronotype-specific neuronal mechanisms. Consequently, results might change the way we schedule patient evaluations and/or healthy subjects in e.g. experimental research and adding "chronotype" as a statistical covariate. PMID:26397824
fMRI Adaptation between Action Observation and Action Execution Reveals Cortical Areas with Mirror Neuron Properties in Human BA 44/45
de la Rosa, Stephan; Schillinger, Frieder L.; Bülthoff, Heinrich H.; Schultz, Johannes; Uludag, Kamil
Mirror neurons (MNs) are considered to be the supporting neural mechanism for action understanding. MNs have been identified in monkey's area F5. The identification of MNs in the human homolog of monkeys' area F5 Broadmann Area 44/45 (BA 44/45) has been proven methodologically difficult. Cross-modal functional MRI (fMRI) adaptation studies supporting the existence of MNs restricted their analysis to a priori candidate regions, whereas studies that failed to find evidence used non-object-directed (NDA) actions. We tackled these limitations by using object-directed actions (ODAs) differing only in terms of their object directedness in combination with a cross-modal adaptation paradigm and a whole-brain analysis. Additionally, we tested voxels' blood oxygenation level-dependent (BOLD) response patterns for several properties previously reported as typical MN response properties. Our results revealed 52 voxels in left inferior frontal gyrus (IFG; particularly BA 44/45), which respond to both motor and visual stimulation and exhibit cross-modal adaptation between the execution and observation of the same action. These results demonstrate that part of human IFG, specifically BA 44/45, has BOLD response characteristics very similar to monkey's area F5. PMID:26973496
The selectivity of responses to red-green colour and achromatic contrast in the human visual cortex: an fMRI adaptation study.
Mullen, Kathy T; Chang, Dorita H F; Hess, Robert F
There is controversy as to how responses to colour in the human brain are organized within the visual pathways. A key issue is whether there are modular pathways that respond selectively to colour or whether there are common neural substrates for both colour and achromatic (Ach) contrast. We used functional magnetic resonance imaging (fMRI) adaptation to investigate the responses of early and extrastriate visual areas to colour and Ach contrast. High-contrast red-green (RG) and Ach sinewave rings (0.5 cycles/degree, 2 Hz) were used as both adapting stimuli and test stimuli in a block design. We found robust adaptation to RG or Ach contrast in all visual areas. Cross-adaptation between RG and Ach contrast occurred in all areas indicating the presence of integrated, colour and Ach responses. Notably, we revealed contrasting trends for the two test stimuli. For the RG test, unselective processing (robust adaptation to both RG and Ach contrast) was most evident in the early visual areas (V1 and V2), but selective responses, revealed as greater adaptation between the same stimuli than cross-adaptation between different stimuli, emerged in the ventral cortex, in V4 and VO in particular. For the Ach test, unselective responses were again most evident in early visual areas but Ach selectivity emerged in the dorsal cortex (V3a and hMT+). Our findings support a strong presence of integrated mechanisms for colour and Ach contrast across the visual hierarchy, with a progression towards selective processing in extrastriate visual areas.
Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.
Pillai, Jay J; Zacà, Domenico
The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion
Resting state fMRI: A review of methods and clinical applications
Lee, Megan H.; Smyser, Christopher D.; Shimony, Joshua S.
Resting state fMRI measures spontaneous, low frequency fluctuations in the BOLD signal to investigate the functional architecture of the brain. Application of this technique has allowed for the identification of various RSNs, or spatially distinct areas of the brain that demonstrate synchronous BOLD fluctuations at rest. Various methods exist for analyzing resting state data, including seed based approaches, independent component analysis, graph methods, clustering algorithms, neural networks, and pattern classifiers. Clinical applications of resting state fMRI are at an early stage of development. However, its use in presurgical planning for brain tumor and epilepsy patients demonstrates early promise, and the technique may also have a future role in providing diagnostic and prognostic information for neurological and psychiatric diseases. PMID:22936095
External awareness and GABA--a multimodal imaging study combining fMRI and [18F]flumazenil-PET.
Wiebking, Christine; Duncan, Niall W; Qin, Pengmin; Hayes, Dave J; Lyttelton, Oliver; Gravel, Paul; Verhaeghe, Jeroen; Kostikov, Alexey P; Schirrmacher, Ralf; Reader, Andrew J; Bajbouj, Malek; Northoff, Georg
Awareness is an essential feature of the human mind that can be directed internally, that is, toward our self, or externally, that is, toward the environment. The combination of internal and external information is crucial to constitute our sense of self. Although the underlying neuronal networks, the so-called intrinsic and extrinsic systems, have been well-defined, the associated biochemical mechanisms still remain unclear. We used a well-established functional magnetic resonance imaging (fMRI) paradigm for internal (heartbeat counting) and external (tone counting) awareness and combined this technique with [(18)F]FMZ-PET imaging in the same healthy subjects. Focusing on cortical midline regions, the results showed that both stimuli types induce negative BOLD responses in the mPFC and the precuneus. Carefully controlling for structured noise in fMRI data, these results were also confirmed in an independent data sample using the same paradigm. Moreover, the degree of the GABAA receptor binding potential within these regions was correlated with the neuronal activity changes associated with external, rather than internal awareness when compared to fixation. These data support evidence that the inhibitory neurotransmitter GABA is an influencing factor in the differential processing of internally and externally guided awareness. This in turn has implications for our understanding of the biochemical mechanisms underlying awareness in general and its potential impact on psychiatric disorders.
Calibrated fMRI in the Medial Temporal Lobe During a Memory Encoding Task
Restom, Khaled; Perthen, Joanna E.; Liu, Thomas T.
Prior measures of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses to a memory encoding task within the medial temporal lobe have suggested that the coupling between functional changes in CBF and changes in the cerebral metabolic rate of oxgyen (CMRO2) may be tighter in the medial temporal lobe as compared to the primary sensory areas. In this study, we used a calibrated functional magnetic resonance imaging (fMRI) approach to directly estimate memory-encoding-related changes in CMRO2 and to assess the coupling between CBF and CMRO2 in the medial temporal lobe. The CBF-CMRO2 coupling ratio was estimated using a linear fit to the flow and metabolism changes observed across subjects. In addition, we examined the effect of region-of-interest (ROI) selection on the estimates. In response to the memory encoding task, CMRO2 increased by 23.1% ± 8.8 to 25.3% ± 5.7 (depending upon ROI), with an estimated CBF-CMRO2 coupling ratio of 1.66 ± 0.07 to 1.75± 0.16. There was not a significant effect of ROI selection on either the CMRO2 or coupling ratio estimates. The observed coupling ratios were significantly lower than the values (2 to 4.5) that have been reported in previous calibrated fMRI studies of the visual and motor cortices. In addition, the estimated coupling ratio was found to be less sensitive to the calibration procedure for functional responses in the medial temporal lobe as compared to the primary sensory areas. PMID:18329291
Neural response to modulating the probability that actions of self or other result in auditory tones: A parametric fMRI study into causal ambiguity.
de Bézenac, Christophe E; Sluming, Vanessa; Gouws, André; Corcoran, Rhiannon
In normal circumstances we can easily distinguish between changes to the external world brought about by our own actions from those with external causes. However, in certain contexts our sense of ownership and agency over acts is not so clear. Neuroimaging studies have implicated a number of regions in the sense of agency, some of which have been shown to vary continuously with action-outcome discordance. However, little is known about dynamic, ambiguous contexts characterised by a lack of information for self-other differentiation, yet such ambiguous states are important in relation to symptoms and levels of consciousness that characterise certain mental health conditions. With a block-design fMRI paradigm, we investigated neural responses to changes in the probability that a participant's irregular finger taps over 12s would result in auditory tones as opposed to tones generated by 'another's finger taps'. The main findings were that misattribution increased in ambiguous conditions where the probability of a tone belonging to self and other was equal. Task-sensitive brain regions, previously identified in self-agency, motor cognition, and ambiguity processing, showed a quadratic response to our self-to-other manipulation, with particular sensitivity to self-control. Task performance (low error and bias) was related to attenuated response in ambiguous conditions while increased response in regions associated with the default mode network was associated with greater overall error and bias towards other. These findings suggest that causal ambiguity as it occurs over time is a prominent feature in sense of agency, one that may eventually contribute to a more comprehensive understanding of positive symptoms of psychosis.
Lack of Evidence That Neural Empathic Responses Are Blunted in Excessive Users of Violent Video Games: An fMRI Study
Szycik, Gregor R.; Mohammadi, Bahram; Münte, Thomas F.; te Wildt, Bert T.
The use of violent video games has been often linked to increase of aggressive behavior. According to the General Aggression Model, one of the central mechanisms for this aggressiveness inducing impact is an emotional desensitization process resulting from long lasting repeated violent game playing. This desensitization should evidence itself in a lack of empathy. Recent research has focused primarily on acute, short term impact of violent media use but only little is known about long term effects. In this study 15 excessive users of violent games and control subjects matched for age and education viewed pictures depicting emotional and neutral situations with and without social interaction while fMRI activations were obtained. While the typical pattern of activations for empathy and theory of mind networks was seen, both groups showed no differences in brain responses. We interpret our results as evidence against the desensitization hypothesis and suggest that the impact of violent media on emotional processing may be rather acute and short-lived. PMID:28337156
Lack of Evidence That Neural Empathic Responses Are Blunted in Excessive Users of Violent Video Games: An fMRI Study.
Szycik, Gregor R; Mohammadi, Bahram; Münte, Thomas F; Te Wildt, Bert T
The use of violent video games has been often linked to increase of aggressive behavior. According to the General Aggression Model, one of the central mechanisms for this aggressiveness inducing impact is an emotional desensitization process resulting from long lasting repeated violent game playing. This desensitization should evidence itself in a lack of empathy. Recent research has focused primarily on acute, short term impact of violent media use but only little is known about long term effects. In this study 15 excessive users of violent games and control subjects matched for age and education viewed pictures depicting emotional and neutral situations with and without social interaction while fMRI activations were obtained. While the typical pattern of activations for empathy and theory of mind networks was seen, both groups showed no differences in brain responses. We interpret our results as evidence against the desensitization hypothesis and suggest that the impact of violent media on emotional processing may be rather acute and short-lived.
Multivoxel Pattern Analysis for fMRI Data: A Review
Takerkart, Sylvain; Regragui, Fakhita; Boussaoud, Driss; Brovelli, Andrea
Functional magnetic resonance imaging (fMRI) exploits blood-oxygen-level-dependent (BOLD) contrasts to map neural activity associated with a variety of brain functions including sensory processing, motor control, and cognitive and emotional functions. The general linear model (GLM) approach is used to reveal task-related brain areas by searching for linear correlations between the fMRI time course and a reference model. One of the limitations of the GLM approach is the assumption that the covariance across neighbouring voxels is not informative about the cognitive function under examination. Multivoxel pattern analysis (MVPA) represents a promising technique that is currently exploited to investigate the information contained in distributed patterns of neural activity to infer the functional role of brain areas and networks. MVPA is considered as a supervised classification problem where a classifier attempts to capture the relationships between spatial pattern of fMRI activity and experimental conditions. In this paper , we review MVPA and describe the mathematical basis of the classification algorithms used for decoding fMRI signals, such as support vector machines (SVMs). In addition, we describe the workflow of processing steps required for MVPA such as feature selection, dimensionality reduction, cross-validation, and classifier performance estimation based on receiver operating characteristic (ROC) curves. PMID:23401720
Exploiting Magnetic Resonance Angiography Imaging Improves Model Estimation of BOLD Signal
Hu, Zhenghui; Liu, Cong; Shi, Pengcheng; Liu, Huafeng
The change of BOLD signal relies heavily upon the resting blood volume fraction () associated with regional vasculature. However, existing hemodynamic data assimilation studies pretermit such concern. They simply assign the value in a physiologically plausible range to get over ill-conditioning of the assimilation problem and fail to explore actual . Such performance might lead to unreliable model estimation. In this work, we present the first exploration of the influence of on fMRI data assimilation, where actual within a given cortical area was calibrated by an MR angiography experiment and then was augmented into the assimilation scheme. We have investigated the impact of on single-region data assimilation and multi-region data assimilation (dynamic cause modeling, DCM) in a classical flashing checkerboard experiment. Results show that the employment of an assumed in fMRI data assimilation is only suitable for fMRI signal reconstruction and activation detection grounded on this signal, and not suitable for estimation of unobserved states and effective connectivity study. We thereby argue that introducing physically realistic in the assimilation process may provide more reliable estimation of physiological information, which contributes to a better understanding of the underlying hemodynamic processes. Such an effort is valuable and should be well appreciated. PMID:22384043
Measurement, time-stamping, and analysis of electrodermal activity in fMRI
NASA Astrophysics Data System (ADS)
Smyser, Christopher; Grabowski, Thomas J.; Rainville, Pierre; Bechara, Antione; Razavi, Mehrdad; Mehta, Sonya; Eaton, Brent L.; Bolinger, Lizann
A low cost fMRI-compatible system was developed for detecting electrodermal activity without inducing image artifact. Subject electrodermal activity was measured on the plantar surface of the foot using a standard recording circuit. Filtered analog skin conductance responses (SCR) were recorded with a general purpose, time-stamping data acquisition system. A conditioning paradigm involving painful thermal stimulation was used to demonstrate SCR detection and investigate neural correlates of conditioned autonomic activity. 128x128 pixel EPI-BOLD images were acquired with a GE 1.5T Signa scanner. Image analysis was performed using voxel-wise multiple linear regression. The covariate of interest was generated by convolving stimulus event onset with a standard hemodynamic response function. The function was time-shifted to determine optimal activation. Significance was tested using the t-statistic. Image quality was unaffected by the device, and conditioned and unconditioned SCRs were successfully detected. Conditioned SCRs correlated significantly with activity in the right anterior insular cortex. The effect was more robust when responses were scaled by SCR amplitude. The ability to measure and time register SCRs during fMRI acquisition enables studies of cognitive processes marked by autonomic activity, including those involving decision-making, pain, emotion, and addiction.
Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI
Brashers-Krug, Tom; Jorge, Ricardo
Objectives Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC) in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent. Methods We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI) session to 50 veterans of recent combat. We collected skin conductance responses (SCRs) as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD) signal in the amygdala and ACC to symptom measures and to SCRs. Results Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala. Conclusions Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The
Language exposure induced neuroplasticity in the bilingual brain: a follow-up fMRI study.
Tu, Liu; Wang, Junjing; Abutalebi, Jubin; Jiang, Bo; Pan, Ximin; Li, Meng; Gao, Wei; Yang, Yuchen; Liang, Bishan; Lu, Zhi; Huang, Ruiwang
Although several studies have shown that language exposure crucially influence the cerebral representation of bilinguals, the effects of short-term change of language exposure in daily life upon language control areas in bilinguals are less known. To explore this issue, we employed follow-up fMRI to investigate whether differential exposure induces neuroplastic changes in the language control network in high-proficient Cantonese (L1)-Mandarin (L2) early bilinguals. The same 10 subjects underwent twice BOLD-fMRI scans while performing a silent narration task which corresponded to two different language exposure conditions, CON-1 (L1/L2 usage percentage, 50%:50%) and CON-2 (L1/L2 usage percentage, 90%:10%). We report a strong effect of language exposure in areas related to language control for the less exposed language. Interestingly, these significant effects were present after only a 30-day period of differential language exposure. In detail, we reached the following results: (1) the interaction effect of language and language exposure condition was found significantly in the left pars opercularis (BA 44) and marginally in the left MFG (BA 9); (2) in CON-2, increases of activation values in L2 were found significantly in bilateral BA 46 and BA 9, in the left BA44, and marginally in the left caudate; and (3) in CON-2, we found a significant negative correlation between language exposure to L2 and the BOLD activation value specifically in the left ACC. These findings strongly support the hypothesis that even short periods of differential exposure to a given language may induce significant neuroplastic changes in areas responsible for language control. The language which a bilingual is less exposed to and is also less used will be in need of increased mental control as shown by the increased activity of language control areas.
One-Class FMRI-Inspired EEG Model for Self-Regulation Training
Kinreich, Sivan; Jackont, Gilan; Cohen, Avihay; Podlipsky-Klovatch, Ilana; Hendler, Talma; Intrator, Nathan
Recent evidence suggests that learned self-regulation of localized brain activity in deep limbic areas such as the amygdala, may alleviate symptoms of affective disturbances. Thus far self-regulation of amygdala activity could be obtained only via fMRI guided neurofeedback, an expensive and immobile procedure. EEG on the other hand is relatively inexpensive and can be easily implemented in any location. However the clinical utility of EEG neurofeedback for affective disturbances remains limited due to low spatial resolution, which hampers the targeting of deep limbic areas such as the amygdala. We introduce an EEG prediction model of amygdala activity from a single electrode. The gold standard used for training is the fMRI-BOLD signal in the amygdala during simultaneous EEG/fMRI recording. The suggested model is based on a time/frequency representation of the EEG data with varying time-delay. Previous work has shown a strong inhomogeneity among subjects as is reflected by the models created to predict the amygdala BOLD response from EEG data. In that work, different models were constructed for different subjects. In this work, we carefully analyzed the inhomogeneity among subjects and were able to construct a single model for the majority of the subjects. We introduce a method for inhomogeneity assessment. This enables us to demonstrate a choice of subjects for which a single model could be derived. We further demonstrate the ability to modulate brain-activity in a neurofeedback setting using feedback generated by the model. We tested the effect of the neurofeedback training by showing that new subjects can learn to down-regulate the signal amplitude compared to a sham group, which received a feedback obtained by a different participant. This EEG based model can overcome substantial limitations of fMRI-NF. It can enable investigation of NF training using multiple sessions and large samples in various locations. PMID:27163677
Functional Laterality of Task-Evoked Activation in Sensorimotor Cortex of Preterm Infants: An Optimized 3 T fMRI Study Employing a Customized Neonatal Head Coil
Smith-Collins, Adam PR; Müller, Nicole; Stegmann-Woessner, Gaby; Jankowski, Jacob; Gieseke, Jürgen; Born, Mark; Seitz, Hermann; Bartmann, Peter; Schild, Hans H.; Pruessmann, Klaas P.; Boecker, Henning
Background Functional magnetic resonance imaging (fMRI) in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD) responses in sensorimotor cortex (SMC). Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level. Patients / methods Here, we employed a custom-designed neonatal MR-coil adapted and optimized to the head size of a newborn in order to improve robustness, reliability and validity of neonatal sensorimotor fMRI. Thirteen preterm infants with a median gestational age of 26 weeks were scanned at term-corrected age using a prototype 8-channel neonatal head coil at 3T (Achieva, Philips, Best, NL). Sensorimotor stimulation was elicited by passive extension/flexion of the elbow at 1 Hz in a block design. Analysis of temporal signal to noise ratio (tSNR) was performed on the whole brain and the SMC, and was compared to data acquired with an 'adult' 8 channel head coil published previously. Task-evoked activation was determined by single-subject SPM8 analyses, thresholded at p < 0.05, whole-brain FWE-corrected. Results Using a custom-designed neonatal MR-coil, we found significant positive BOLD responses in contralateral SMC after unilateral passive sensorimotor stimulation in all neonates (analyses restricted to artifact-free data sets = 8/13). Improved imaging characteristics of the neonatal MR-coil were evidenced by additional phantom and in vivo tSNR measurements: phantom studies revealed a 240% global increase in tSNR; in vivo studies revealed a 73% global and a 55% local (SMC) increase in tSNR, as compared to the 'adult' MR
Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal
Harris, Samuel; Bruyns-Haylett, Michael; Kennerley, Aneurin; Zheng, Ying; Martin, Chris; Jones, Myles; Redgrave, Peter; Berwick, Jason
Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to "negative" hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30–80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals. PMID:25788681
Making the most of fMRI at 7 T by suppressing spontaneous signal fluctuations.
Bianciardi, Marta; van Gelderen, Peter; Duyn, Jeff H; Fukunaga, Masaki; de Zwart, Jacco A
The presence of spontaneous BOLD fMRI signal fluctuations in human grey matter compromises the detection and interpretation of evoked responses and limits the sensitivity gains that are potentially available through coil arrays and high field systems. In order to overcome these limitations, we adapted and improved a recently described correlated noise suppression method (de Zwart et al., 2008), demonstrating improved precision in estimating the response to ultra-short visual stimuli at 7 T. In this procedure, the temporal dynamics of spontaneous signal fluctuations are estimated from a reference brain region outside the area targeted with the stimulus. Rather than using the average signal in this region as regressor, as proposed in the original method, we used principal component analysis to derive multiple regressors in order to optimally describe nuisance signals (e.g. spontaneous fluctuations) and separate these from evoked activity in the target region. Experimental results obtained from application of the original method showed a 66% improvement in estimation precision. The novel, enhanced version of the method, using 18 PCA-derived noise regressors, led to a 160% increase in precision. These increases were relative to a control condition without noise suppression, which was simulated by randomizing the time-course of the nuisance-signal regressor(s) without altering their power spectrum. The increase of estimation precision was associated with decreased autocorrelation levels of the residual errors. These results suggest that modeling of spontaneous fMRI signal fluctuations as multiple independent sources can dramatically improve detection of evoked activity, and fully exploit the potential sensitivity gains available with high field technology.
Scent of the familiar: an fMRI study of canine brain responses to familiar and unfamiliar human and dog odors.
Berns, Gregory S; Brooks, Andrew M; Spivak, Mark
Understanding dogs' perceptual experience of both conspecifics and humans is important to understand how dogs evolved and the nature of their relationships with humans and other dogs. Olfaction is believed to be dogs' most powerful and perhaps important sense and an obvious place to begin for the study of social cognition of conspecifics and humans. We used fMRI in a cohort of dogs (N=12) that had been trained to remain motionless while unsedated and unrestrained in the MRI. By presenting scents from humans and conspecifics, we aimed to identify the dimensions of dogs' responses to salient biological odors - whether they are based on species (dog or human), familiarity, or a specific combination of factors. We focused our analysis on the dog's caudate nucleus because of its well-known association with positive expectations and because of its clearly defined anatomical location. We hypothesized that if dogs' primary association to reward, whether it is based on food or social bonds, is to humans, then the human scents would activate the caudate more than the conspecific scents. Conversely, if the smell of conspecifics activated the caudate more than the smell of humans, dogs' association to reward would be stronger to their fellow canines. Five scents were presented (self, familiar human, strange human, familiar dog, strange dog). While the olfactory bulb/peduncle was activated to a similar degree by all the scents, the caudate was activated maximally to the familiar human. Importantly, the scent of the familiar human was not the handler, meaning that the caudate response differentiated the scent in the absence of the person being present. The caudate activation suggested that not only did the dogs discriminate that scent from the others, they had a positive association with it. This speaks to the power of the dog's sense of smell, and it provides important clues about the importance of humans in dogs' lives. This article is part of a Special Issue entitled: Canine
Attention Diversion Improves Response Inhibition of Immediate Reward, But Only When it Is Beneficial: An fMRI Study
Scalzo, Franco; O'Connor, David A.; Orr, Catherine; Murphy, Kevin; Hester, Robert
Deficits of self-control are associated with a number of mental state disorders. The ability to direct attention away from an alluring stimulus appears to aid inhibition of an impulsive response. However, further functional imaging research is required to assess the impact of shifts in attention on self-regulating processes. We varied the level of attentional disengagement in an functional magnetic resonance imaging (fMRI)-based Go/No-go task to probe whether diversion of attention away from alluring stimuli facilitates response inhibition. We used the attention-grabbing characteristic of faces to exogenously direct attention away from stimuli and investigated the relative importance of attention and response inhibition mechanisms under different delayed reward scenarios [i.e., where forgoing an immediate reward ($1) led to a higher ($10) or no payoff in the future]. We found that diverting attention improved response inhibition performance, but only when resistance to an alluring stimulus led to delayed reward. Region of interest analyses indicated significant increased activity in posterior right inferior frontal gyrus during successful No-go trials for delayed reward trials compared to no delayed reward trials, and significant reduction in activity in the superior temporal gyri and left caudate in contexts of high attentional diversion. Our findings imply that strategies that increase the perceived benefits of response inhibition might assist individuals in abstaining from problematic impulsive behaviors. PMID:27616988
Self-responsibility and the self-serving bias: an fMRI investigation of causal attributions.
Blackwood, N J; Bentall, R P; ffytche, D H; Simmons, A; Murray, R M; Howard, R J
We use causal attributions to infer the most likely cause of events in the social world. Internal attributions imply self-responsibility for events. The self-serving bias describes the tendency of normal subjects to attribute the causation of positive events internally ("I am responsible em leader ") and negative events externally ("Other people or situational factors are responsible em leader "). The self-serving bias has been assumed to serve a positive motivational function by enhancing self-esteem. Abnormalities of attributional style have been implicated in both depression and psychosis. We examined the neural basis of both self-responsibility and the self-serving bias using functional magnetic resonance imaging during the performance of attributional decision tasks. We found that the determination of self-responsibility recruits areas previously implicated in action simulation (bilateral premotor cortex and cerebellum), suggesting that such higher order social cognition is related to simpler internal models of goal-directed action. The dorsal striatum, previously implicated in motivated behavior, mediates the self-serving bias.
Increasing fMRI sampling rate improves Granger causality estimates.
Lin, Fa-Hsuan; Ahveninen, Jyrki; Raij, Tommi; Witzel, Thomas; Chu, Ying-Hua; Jääskeläinen, Iiro P; Tsai, Kevin Wen-Kai; Kuo, Wen-Jui; Belliveau, John W
Estimation of causal interactions between brain areas is necessary for elucidating large-scale functional brain networks underlying behavior and cognition. Granger causality analysis of time series data can quantitatively estimate directional information flow between brain regions. Here, we show that such estimates are significantly improved when the temporal sampling rate of functional magnetic resonance imaging (fMRI) is increased 20-fold. Specifically, healthy volunteers performed a simple visuomotor task during blood oxygenation level dependent (BOLD) contrast based whole-head inverse imaging (InI). Granger causality analysis based on raw InI BOLD data sampled at 100-ms resolution detected the expected causal relations, whereas when the data were downsampled to the temporal resolution of 2 s typically used in echo-planar fMRI, the causality could not be detected. An additional control analysis, in which we SINC interpolated additional data points to the downsampled time series at 0.1-s intervals, confirmed that the improvements achieved with the real InI data were not explainable by the increased time-series length alone. We therefore conclude that the high-temporal resolution of InI improves the Granger causality connectivity analysis of the human brain.
High responsivity to threat during the initial stage of perception in repression: a 3 T fMRI study
Paul, Victoria Gabriele; Rauch, Astrid Veronika; Kugel, Harald; ter Horst, Lena; Bauer, Jochen; Dannlowski, Udo; Ohrmann, Patricia; Lindner, Christian; Donges, Uta-Susan; Kersting, Anette; Egloff, Boris
Repression designates coping strategies such as avoidance, or denial that aim to shield the organism from threatening stimuli. Derakshan et al. have proposed the vigilance–avoidance theory of repressive coping. It is assumed that repressors have an initial rapid vigilant response triggering physiological responses to threat stimuli. In the following second stage repressors manifest avoidant cognitive biases. Functional magnetic resonance imaging at 3T was used to study neural correlates of repressive coping during the first stages of perception of threat. Pictures of human faces bearing fearful, angry, happy and neutral expressions were briefly presented masked by neutral faces. Forty study participants (20 repressive and 20 sensitizing individuals) were selected from a sample of 150 female students on the basis of their scores on the Mainz Coping Inventory. Repressors exhibited stronger neural activation than sensitizers primarily in response to masked threatening faces (vs neutral baseline) in the frontal, parietal and temporal cortex as well as in the cingulate gyrus, basal ganglia and insula. There was no brain region in which sensitizers showed increased activation to emotion expression compared to repressors. The present results are in line with the vigilance–avoidance theory which predicts heightened automatic responsivity to threatening stimuli in repression. PMID:22133562
Visual sexual stimulation and erection, a brief review with new fMRI data.
Wu, Sharon L; Chow, Maggie Sm; Jiang, Y L; Yang, Jingjin; Zhou, Hao; Yew, David T
This review examines brain sites involved in sexual stimulation. New data on brain activation sites in individuals having erections concomitant with visual erotic stimulation was documented. The activation was chiefly at the midbrain around the cerebral peduncle, and in the pons centering on the tegmentum, they are indicated by blood oxygenation level dependent (BOLD) images captured by functional magnetic resonance imaging (fMRI). The cerebellum and inferior temporal lobe were activated more extensively in individuals viewing pornographic movie with a concomitant erection than those without. Similarly, individuals with erection had activation in the midbrain and pons, while drug addicts had neither erections nor any of these brainstem active sites. From our observation in the new data, we deduced three possible transmitters might be involved in erection: i) cholinergic neurons forming descending pathways and associated with motor activity ii) gamma-aminobutyric acid (GABA), directly or indirectly via decreasing pathways, modulating autonomic vascular responses in the penile vasculature causing the filling of blood iii) GABA decreases to stimulate dopamine increase in ventral tegmentum of the brain, leading to euphoric responses.
Neural correlates of an illusory touch experience investigated with fMRI.
Lloyd, Donna M; McKenzie, Kirsten J; Brown, Richard J; Poliakoff, Ellen
When asked to judge the presence or absence of near-threshold tactile stimuli, participants often report touch experiences when no tactile stimulation has been delivered ('false alarms'). The simultaneous presentation of a light flash during the stimulation period can increase the frequency of touch reports, both when touch is and is not present. Using fMRI, we investigated the BOLD response during both light-present and light-absent false alarms, testing predictions concerning two possible neural mechanisms underlying these illusory touch experiences: activation of a tactile representation in primary somatosensory cortex (SI) and/or activation of a tactile representation in late processing areas outside of sensory-specific cortex, such as medial prefrontal cortex (MPC). Our behavioural results showed that participants made false alarms in light-present and light-absent trials, both of which activated regions of the medial parietal and medial prefrontal cortex including precuneus, posterior cingulate and paracingulate cortex, suggesting the same underlying mechanism. However, only a non-significant increase in SI activity was measured in response to false alarm vs. correct rejection trials. We argue that our results provide evidence for the role of top-down regions in somatic misperception, consistent with findings from studies in humans and non-human primates.
Comparison of the hemodynamic response to different visual stimuli in single-event and block stimulation fMRI experiments.
Janz, C; Schmitt, C; Speck, O; Hennig, J
Experiments with three different types of basic visual stimulation were performed to compare cortical activation in single-event and block trials. Independent of the stimulation paradigm, the single-event presentation leads to highly consistent signal responses regarding both the activated cortical areas and the dynamics of the signal time course. In contrast, signal time courses during block paradigms depend on the stimulus applied and are a complex and nonlinear function of the single-event responses. Additionally, the initial dip during the first 2 seconds after stimulus onset is consistently observed. However, the small amplitude change (-0.1% to -0.3%) requires signal averaging to establish statistical significance of the effect. Furthermore, different patterns of activation were observed within the primary visual cortex. In an anterior part of the primary visual cortex, activation was only observed at the onset and at the cessation of stimulation involving luminance changes.
The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions
Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L
Background Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. Methods This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Results Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). Conclusions As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits. PMID:25161824
Using pulse oximetry to account for high and low frequency physiological artifacts in the BOLD signal.
Verstynen, Timothy D; Deshpande, Vibhas
The BOLD signal not only reflects changes in local neural activity, but also exhibits variability from physiological processes like cardiac rhythms and breathing. We investigated how both of these physiological sources are reflected in the pulse oximetry (PO) signal, a direct measure of blood oxygenation, and how this information can be used to account for different types of noise in the BOLD response. Measures of heart rate, respiration and PO were simultaneously recorded while neurologically healthy participants performed an eye-movement task in a 3T MRI. PO exhibited power in frequencies that matched those found in the independently recorded cardiac and respiration signals. Using the phasic and aphasic properties of these signals as nuisance regressors, we found that the different frequency components of the PO signal could be used to identify different types of physiological artifacts in the BOLD response. A comparison of different physiological noise models found that a simple, down-sampled version of the PO signal improves the estimation of task-relevant statistics nearly as well as more established noise models that may run the risk of over-parameterization. These findings suggest that the PO signal captures multiple sources of physiological noise in the BOLD response and provides a simple and efficient way of modeling these noise sources in subsequent analysis.
Prequit fMRI Responses to Pleasant Cues and Cigarette-Related Cues Predict Smoking Cessation Outcome
Introduction: The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. Methods: Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. Results: Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. Conclusions: Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence. PMID:24376278
Fractal analysis of spontaneous fluctuations of the BOLD signal in rat brain
Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Eke, Andras
Analysis of task-evoked fMRI data ignores low frequency fluctuations (LFF) of the resting-state the BOLD signal, yet LFF of the spontaneous BOLD signal is crucial for analysis of resting-state connectivity maps. We characterized the LFF of resting-state BOLD signal at 11.7T in α-chloralose and domitor anesthetized rat brain and modeled the spontaneous signal as a scale-free (i.e., fractal) distribution of amplitude power (∣A∣2) across a frequency range (f) compatible with an ∣A(f)∣2 ∝ 1/fβ model where β is the scaling exponent (or spectral index). We compared β values from somatosensory forelimb area (S1FL), cingulate cortex (CG), and caudate putamen (CPu). With α-chloralose, S1FL and CG β values dropped from ~0.7 at in vivo to ~0.1 at post mortem (p<0.0002), whereas CPu β values dropped from ~0.3 at in vivo to ~0.1 at post mortem (p<0.002). With domitor, cortical (S1FL, CG) β values were slightly higher than with α-chloralose, while subcortical (CPu) β values were similar with α-chloralose. Although cortical and subcortical β values with both anesthetics were significantly different in vivo (p<0.002), at post mortem β values in these regions were not significantly different and approached zero (i.e., range of −0.1 to 0.2). Since a water phantom devoid of susceptibility gradients had a β value of zero (i.e., random), we conclude that deoxyhemoglobin present in voxels post-sacrifice still impacts tissue water diffusion. These results suggest that in the anesthetized rat brain the LFF of BOLD signal at 11.7T follow a general 1/fβ model of fractality where β is a variable responding to physiology. We describe typical experimental pitfalls which may elude detection of fractality in the resting-state BOLD signal. PMID:21777682
Branding and a child's brain: an fMRI study of neural responses to logos
Bruce, Jared M.; Black, William R.; Lepping, Rebecca J.; Henry, Janice M.; Cherry, Joseph Bradley C.; Martin, Laura E.; Papa, Vlad B.; Davis, Ann M.; Brooks, William M.; Savage, Cary R.
Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing. PMID:22997054
Bartelle, Benjamin B.; Barandov, Ali
Comprehensive analysis of brain function depends on understanding the dynamics of diverse neural signaling processes over large tissue volumes in intact animals and humans. Most existing approaches to measuring brain signaling suffer from limited tissue penetration, poor resolution, or lack of specificity for well-defined neural events. Here we discuss a new brain activity mapping method that overcomes some of these problems by combining MRI with contrast agents sensitive to neural signaling. The goal of this "molecular fMRI" approach is to permit noninvasive whole-brain neuroimaging with specificity and resolution approaching current optical neuroimaging methods. In this article, we describe the context and need for molecular fMRI as well as the state of the technology today. We explain how major types of MRI probes work and how they can be sensitized to neurobiological processes, such as neurotransmitter release, calcium signaling, and gene expression changes. We comment both on past work in the field and on challenges and promising avenues for future development. SIGNIFICANCE STATEMENT Brain researchers currently have a choice between measuring neural activity using cellular-level recording techniques, such as electrophysiology and optical imaging, or whole-brain imaging methods, such as fMRI. Cellular level methods are precise but only address a small portion of mammalian brains; on the other hand, whole-brain neuroimaging techniques provide very little specificity for neural pathways or signaling components of interest. The molecular fMRI techniques we discuss have particular potential to combine the specificity of cellular-level measurements with the noninvasive whole-brain coverage of fMRI. On the other hand, molecular fMRI is only just getting off the ground. This article aims to offer a snapshot of the status and future prospects for development of molecular fMRI techniques. PMID:27076413
Physiological brainstem mechanisms of trigeminal nociception: An fMRI study at 3T.
Schulte, Laura H; Sprenger, Christian; May, Arne
The brainstem is a major site of processing and modulation of nociceptive input and plays a key role in the pathophysiology of various headache disorders. However, human imaging studies on brainstem function following trigeminal nociceptive stimulation are scarce as brainstem specific imaging approaches have to address multiple challenges such as magnetic field inhomogeneities and an enhanced level of physiological noise. In this study we used a viable protocol for brainstem fMRI of standardized trigeminal nociceptive stimulation to achieve detailed insight into physiological brainstem mechanisms of trigeminal nociception. We conducted a study of 21 healthy participants using a nociceptive ammonia stimulation of the left nasal mucosa with an optimized MR acquisition protocol for high resolution brainstem echoplanar imaging in combination with two different noise correction techniques. Significant BOLD responses to noxious ammonia stimulation were observed in areas typically involved in trigeminal nociceptive processing such as the spinal trigeminal nuclei (sTN), thalamus, secondary somatosensory cortex, insular cortex and cerebellum as well as in a pain modulating network including the periaqueductal gray area, hypothalamus (HT), locus coeruleus and cuneiform nucleus (CNF). Activations of the left CNF were positively correlated with pain intensity ratings. Employing psychophysiological interaction (PPI) analysis we found enhanced functional connectivity of the sTN with the contralateral sTN and HT following trigeminal nociception. We also observed enhanced functional connectivity of the CNF with the RVM during painful stimulation thus implying an important role of these two brainstem regions in central pain processing. The chosen approach to study trigeminal nociception with high-resolution fMRI offers new insight into human pain processing and might thus lead to a better understanding of headache pathophysiology.
Nonlinear Bayesian Estimation of BOLD Signal under Non-Gaussian Noise
Khan, Ali Fahim; Younis, Muhammad Shahzad; Bajwa, Khalid Bashir
Modeling the blood oxygenation level dependent (BOLD) signal has been a subject of study for over a decade in the neuroimaging community. Inspired from fluid dynamics, the hemodynamic model provides a plausible yet convincing interpretation of the BOLD signal by amalgamating effects of dynamic physiological changes in blood oxygenation, cerebral blood flow and volume. The nonautonomous, nonlinear set of differential equations of the hemodynamic model constitutes the process model while the weighted nonlinear sum of the physiological variables forms the measurement model. Plagued by various noise sources, the time series fMRI measurement data is mostly assumed to be affected by additive Gaussian noise. Though more feasible, the assumption may cause the designed filter to perform poorly if made to work under non-Gaussian environment. In this paper, we present a data assimilation scheme that assumes additive non-Gaussian noise, namely, the e-mixture noise, affecting the measurements. The proposed filter MAGSF and the celebrated EKF are put to test by performing joint optimal Bayesian filtering to estimate both the states and parameters governing the hemodynamic model under non-Gaussian environment. Analyses using both the synthetic and real data reveal superior performance of the MAGSF as compared to EKF. PMID:25691911
Input permutation method to detect active voxels in fMRI study☆
Lee, Sang H.; Lim, Johan; Park, DoHwan; Biswal, Bharat B.; Petkova, Eva
Correctly identifying voxels or regions of interest (ROI) that actively respond to a given stimulus is often an important objective/step in many functional magnetic resonance imaging (fMRI) studies. In this article, we study a nonparametric method to detect active voxels, which makes minimal assumption about the distribution of blood oxygen level-dependent (BOLD) signals. Our proposal has several interesting features. It uses time lagged correlation to take into account the delay in response to the stimulus, due to hemodynamic variations. We introduce an input permutation method (IPM), a type of block permutation method, to approximate the null distribution of the test statistic. Also, we propose to pool the permutation-derived statistics of preselected voxels for a better approximation to the null distribution. Finally, we control multiple testing error rate using the local false discovery rate (FDR) by Efron [Correlation and large-scale simultaneous hypothesis testing. J Am Stat Assoc 102 (2007) 93–103] and Park et al. [Estimation of empirical null using a mixture of normals and its use in local false discovery rate. Comput Stat Data Anal 55 (2011) 2421–2432] to select the active voxels. PMID:22819177
Visioning in the brain: an fMRI study of inspirational coaching and mentoring.
Jack, Anthony I; Boyatzis, Richard E; Khawaja, Masud S; Passarelli, Angela M; Leckie, Regina L
Effective coaching and mentoring is crucial to the success of individuals and organizations, yet relatively little is known about its neural underpinnings. Coaching and mentoring to the Positive Emotional Attractor (PEA) emphasizes compassion for the individual's hopes and dreams and has been shown to enhance a behavioral change. In contrast, coaching to the Negative Emotional Attractor (NEA), by focusing on externally defined criteria for success and the individual's weaknesses in relation to them, does not show sustained change. We used fMRI to measure BOLD responses associated with these two coaching styles. We hypothesized that PEA coaching would be associated with increased global visual processing and with engagement of the parasympathetic nervous system (PNS), while the NEA coaching would involve greater engagement of the sympathetic nervous system (SNS). Regions showing more activity in PEA conditions included the lateral occipital cortex, superior temporal cortex, medial parietal, subgenual cingulate, nucleus accumbens, and left lateral prefrontal cortex. We relate these activations to visioning, PNS activity, and positive affect. Regions showing more activity in NEA conditions included medial prefrontal regions and right lateral prefrontal cortex. We relate these activations to SNS activity, self-trait attribution and negative affect.
Changing channels: an fMRI study of aging and cross-modal attention shifts.
Townsend, Jeanne; Adamo, Maha; Haist, Frank
Age-related deficits in visual selective attention suggest that the efficiency of inhibitory processes is particularly affected by aging. To investigate whether processing inefficiencies observed in visual attention are similar in auditory attention and when shifting attention across modalities, we conducted an fMRI study with healthy young and older adults using a task that required sustained auditory and visual selective attention and cross-modal attention shifts. Older adults in this study performed as well as the younger adults, but showed age-related differences in BOLD responses. The most striking of these differences were bilateral frontal and parietal regions of significantly increased activation in older adults during both focused and shifting attention. Our data suggest that this increased activation did not reflect new recruitment, but reliance on brain regions typically used by younger adults when task demands are greater. Older adults' activation patterns suggested that even during focused attention conditions they were "shifting" attention to stimuli in the unattended modality. Increased activation during processing of both task-relevant and task-irrelevant information implies age-related loss of processing selectivity. These patterns may reflect both task-specific compensatory neural recruitment and degradation of sensory inhibition.
Weed or wheel! FMRI, behavioural, and toxicological investigations of how cannabis smoking affects skills necessary for driving.
Battistella, Giovanni; Fornari, Eleonora; Thomas, Aurélien; Mall, Jean-Frédéric; Chtioui, Haithem; Appenzeller, Monique; Annoni, Jean-Marie; Favrat, Bernard; Maeder, Philippe; Giroud, Christian
Marijuana is the most widely used illicit drug, however its effects on cognitive functions underlying safe driving remain mostly unexplored. Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task. The subject characteristics, the percentage of Δ(9)-Tetrahydrocannabinol in the joint, and the inhaled dose were in accordance with real-life conditions. Thirty-one male volunteers were enrolled in this study that includes clinical and toxicological aspects together with functional magnetic resonance imaging of the brain and measurements of psychomotor skills. The fMRI paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. We show that cannabis smoking, even at low Δ(9)-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition. The relative decrease of Blood Oxygen Level Dependent response (BOLD) after cannabis smoking in the anterior insula, dorsomedial thalamus, and striatum compared to placebo smoking suggests an alteration of the network involved in saliency detection. In addition, the decrease of BOLD response in the right superior parietal cortex and in the dorsolateral prefrontal cortex indicates the involvement of the Control Executive network known to operate once the saliencies are identified. Furthermore, cannabis increases activity in the rostral anterior cingulate cortex and ventromedial prefrontal cortices, suggesting an increase in self-oriented mental activity. Subjects are more attracted by intrapersonal stimuli ("self") and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance. These effects correlate with the subjective feeling of confusion rather than with the blood level of Δ(9)-Tetrahydrocannabinol
A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex
Hutchison, Joanna Lynn; Shokri-Kojori, Ehsan; Lu, Hanzhang; Rypma, Bart
Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (ΔCBF) in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (ΔCMRO2). Reductions in ΔCBF responsiveness to increased ΔCMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ΔCBF/ΔCMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ΔCBF/ΔCMRO2. A simulation of BOLD relative to ΔCMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task
Adaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder.
Andari, Elissar; Richard, Nathalie; Leboyer, Marion; Sirigu, Angela
The neuropeptide oxytocin (OT) is one of the major targets of research in neuroscience, with respect to social functioning. Oxytocin promotes social skills and improves the quality of face processing in individuals with social dysfunctions such as autism spectrum disorder (ASD). Although one of OT's key functions is to promote social behavior during dynamic social interactions, the neural correlates of this function remain unknown. Here, we combined acute intranasal OT (IN-OT) administration (24 IU) and fMRI with an interactive ball game and a face-matching task in individuals with ASD (N = 20). We found that IN-OT selectively enhanced the brain activity of early visual areas in response to faces as compared to non-social stimuli. OT inhalation modulated the BOLD activity of amygdala and hippocampus in a context-dependent manner. Interestingly, IN-OT intake enhanced the activity of mid-orbitofrontal cortex in response to a fair partner, and insula region in response to an unfair partner. These OT-induced neural responses were accompanied by behavioral improvements in terms of allocating appropriate feelings of trust toward different partners' profiles. Our findings suggest that OT impacts the brain activity of key areas implicated in attention and emotion regulation in an adaptive manner, based on the value of social cues.
Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries.
Zhang, Jiang; Yuan, Zhen; Huang, Jin; Yang, Qin; Chen, Huafu
Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.
Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands.
Deligianni, Fani; Centeno, Maria; Carmichael, David W; Clayden, Jonathan D
Whole brain functional connectomes hold promise for understanding human brain activity across a range of cognitive, developmental and pathological states. So called resting-state (rs) functional MRI studies have contributed to the brain being considered at a macroscopic scale as a set of interacting regions. Interactions are defined as correlation-based signal measurements driven by blood oxygenation level dependent (BOLD) contrast. Understanding the neurophysiological basis of these measurements is important in conveying useful information about brain function. Local coupling between BOLD fMRI and neurophysiological measurements is relatively well defined, with evidence that gamma (range) frequency EEG signals are the closest correlate of BOLD fMRI changes during cognitive processing. However, it is less clear how whole-brain network interactions relate during rest where lower frequency signals have been suggested to play a key role. Simultaneous EEG-fMRI offers the opportunity to observe brain network dynamics with high spatio-temporal resolution. We utilize these measurements to compare the connectomes derived from rs-fMRI and EEG band limited power (BLP). Merging this multi-modal information requires the development of an appropriate statistical framework. We relate the covariance matrices of the Hilbert envelope of the source localized EEG signal across bands to the covariance matrices derived from rs-fMRI with the means of statistical prediction based on sparse Canonical Correlation Analysis (sCCA). Subsequently, we identify the most prominent connections that contribute to this relationship. We compare whole-brain functional connectomes based on their geodesic distance to reliably estimate the performance of the prediction. The performance of predicting fMRI from EEG connectomes is considerably better than predicting EEG from fMRI across all bands, whereas the connectomes derived in low frequency EEG bands resemble best rs-fMRI connectivity.
A novel technique for examining human brain activity associated with pedaling using fMRI.
Mehta, Jay P; Verber, Matthew D; Wieser, Jon A; Schmit, Brian D; Schindler-Ivens, Sheila M
Advances in neural imaging technologies, such as functional magnetic resonance imaging (fMRI), have made it possible to obtain images of human brain activity during motor tasks. However, technical challenges have made it difficult to image the brain during multijoint lower limb movements like those involved in locomotion. We developed an MR compatible pedaling device and recorded human brain activity associated with rhythmic, alternating flexion and extension of the lower extremities. Ten volunteers pedaled at 30 RPM while recording fMRI signals in a GE 3T short bore MR scanner. We utilized a block design consisting of 3 runs of pedaling, each lasting 4 min. In a single run, subjects pedaled for 30 s and then rested for 30 s. This sequence was repeated 4 times. Conventional fMRI processing techniques, that correlate the entire BOLD signal with standard model, did not extract physiologically meaningful signal, likely due to magnetic field distortion caused by leg movement. Hence, we examined only the portion of the blood-oxygen-level dependent (BOLD) signal during movement-free periods. This technique takes advantage of the delayed nature of the BOLD signal and fits the falling portion of the signal after movement has stopped with a standard model. Using this approach, we observed physiologically plausible brain activity patterns associated with pedaling in the primary and secondary sensory and motor cortices and the cerebellum. To our knowledge, this is the first time that human brain activity associated with pedaling has been recorded with fMRI. This technique may be useful for advancing our understanding of supraspinal control of locomotor-like movements in health and disease.
Validation of the hypercapnic calibrated fMRI method using DOT-fMRI fusion imaging
Yücel, Meryem A.; Evans, Karleyton C.; Selb, Juliette; Huppert, Theodore J.; Boas, David A.; Gagnon, Louis
Calibrated functional Magnetic Resonance Imaging (fMRI) is a widely used method to investigate brain function in terms of physiological quantities such as the cerebral metabolic rate of oxygen (CMRO2). The first and one of the most common methods of fMRI calibration is hypercapnic calibration. This is achieved via simultaneous measures of blood-oxygenation-level dependent (BOLD) and the arterial spin labeling (ASL) signals during a functional task that evokes regional changes in CMRO2. A subsequent acquisition is then required during which the subject inhales carbon dioxide for short periods of time. A calibration constant, typically labeled M, is then estimated from the hypercapnic data and is subsequently used together with the BOLD-ASL recordings to compute evoked changes in CMRO2 during the functional task. The computation of M assumes a constant CMRO2 during the CO2 inhalation, an assumption that has been questioned since the origin of calibrated fMRI. In this study we used Diffuse Optical Tomography (DOT) together with BOLD and ASL – an alternative calibration method that does not require any gas manipulation and therefore no constant CMRO2 assumption - to cross-validate the estimation of M obtained from a traditional hypercapnic calibration. We found a high correlation between the M values (R=0.87, p<0.01) estimated using these two approaches. The findings serve to validate the hypercapnic fMRI calibration technique and suggest that the inter-subject variability routinely obtained for M is reproducible with an alternative method and might therefore reflect inter-subject physiological variability. PMID:25196509
The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults
Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.
Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects
The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.
Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Davis, Simon W; Shafto, Meredith A; Taylor, Jason R; Williams, Nitin; Cam-Can; Rowe, James B
In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task
Target image search using fMRI signals
NASA Astrophysics Data System (ADS)
Xiong, Shi; Song, Sutao; Zhan, Yu; Zhang, Jiacai
Recent neural signal decoding studies based on functional magnetic resonance imaging (fMRI) have identified the specific image presenting to the subject from a set of potential images, and some studies extend neural decoding into image reconstruction, i.e. image contents that the subject perceived were decoded from the fMRI signals recorded during the subject looking at images. In this paper, we decoded the target images using fMRI signals and described a target image searching method based on the relationship between target image stimuli and fMRI activity. We recorded fMRI data during a serial visual stimuli image presentation task, some of the stimuli images were target images and the rest images were non-target ones. Our fMRI data analysis results showed that in the serial visual presentation task, target images elicited a stereotypical response in the fMRI, which can be detected by multi-voxel pattern analysis (MVPA). Classifiers designed with support vector machine (SVM) used this response to decipher target images from non-target images. The leave-one-run-out cross-validation showed that we can pick out the target images with a possibility far above the chance level, which indicate that there's a neural signatures correlated with the target image recognition process in the human systems.
17 CFR 232.307 - Bold face type.
Code of Federal Regulations, 2013 CFR
... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...
17 CFR 232.307 - Bold face type.
Code of Federal Regulations, 2012 CFR
... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...
17 CFR 232.307 - Bold face type.
Code of Federal Regulations, 2014 CFR
... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...
17 CFR 232.307 - Bold face type.