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Attentional Networks in Adolescents with High-functioning Autism: An fMRI Investigation
Hames, Elizabeth C.
Rajmohan, Ravi
Fang, Dan
Anderson, Ronald
Baker, Mary
Richman, David M.
O'Boyle, Michael
The Open Neuroimaging Journal
Attentional deficits in Autism spectrum disorder (ASD) are often noted, but their specific nature remains unclear.
The present study used the child Attentional Network Task (Child ANT) in combination with functional magnetic resonance imaging (fMRI) to determine if the consistently cited deficits of orienting attention are truly due to dysfunctions of orienting-based networks. We hypothesized that these observations are, in fact, a reflection of executive dysfunctions. As such, we expected that although ASD adolescents would perform worse on the orienting portion of the Child ANT, the strongest differences in activation between them and the neurotypical (NT) control group would be in areas classically associated with executive functioning (e.g., the frontal gyri and anterior cingulate cortex).
The brain activity of six high-functioning adolescents with ASD and six NT adolescents was recorded while these individuals performed the three subcomponents of the Child ANT.
ASDs were shown to be more accurate than NTs for the alerting, less accurate for the orienting, and similar in accuracy for the executive portions of the Child ANT. fMRI data showed increased bilateral frontal gyri recruitment, areas conventionally associated with executive control, during the orienting task for the ASD group.
We submit that the increased activations represent neurocorrelates of signal fixation attributable to the subset of executive control responsible for sustained maintenance signals, not the main components of orienting. Therefore, excessive fixation in ASD adolescents is likely due to dysfunctions of executive control and not the orienting subcomponent of the attention network.
Adolescents; ASD; Attention; Executive control; FMRI; High-functioning autism
Related Articles
Attentional networks in children and adolescents with autism spectrum disorder
Keehn, Brandon
Lincoln, Alan J.
Müller, Ralph-Axel
Townsend, Jeanne
Journal of child psychology and psychiatry, and allied disciplines
Individuals diagnosed with autism spectrum disorder (ASD) exhibit lifelong abnormalities in the adaptive allocation of visual attention. The ubiquitous nature of attentional impairments in ASD has led some authors to hypothesize that atypical attentional modulation may be a factor in the development of higher-level sociocommunicative deficits.
Participants were 20 children with ASD and 20 age- and Nonverbal IQ-matched typically developing (TD) children. We used the Attention Network Test (ANT) to investigate the efficiency and independence of three discrete attentional networks: alerting, orienting, and executive control. Additionally, we sought to investigate the relationship between each attentional network and measures of sociocommunicative symptom severity in children with ASD.
Results indicate that the orienting, but not alerting or executive control, networks may be impaired in children with ASD. In contrast to TD children, correlational analyses suggest that the alerting and executive control networks may not function as independently in children with ASD. Additionally, an association was found between the alerting network and social impairment and between the executive control network and IQ in children with ASD.
The results provide further evidence of an impairment in the visuospatial orienting network in ASD and suggest that there may be greater interdependence of alerting and executive control networks in ASD. Furthermore, decreased ability to efficiently modulate levels of alertness was related to increased sociocommunicative deficits, suggesting that domain-general attentional function may be associated with ASD symptomatology.
Autism; reaction time; visual attention; alerting; orienting; executive control
Related Articles
Striatal development in autism: repetitive behaviors and the reward circuitry
Kohls, Gregor
Yerys, Benjamin
Schultz, Robert T.
Biological psychiatry
Autism spectrum disorder (ASD) is defined by two essential features – impaired social communication abilities, including deficits with social reciprocity, nonverbal communication and establishing relationships, and by the presence of restricted and repetitive behaviors and interests (RRBIs). Social deficits get the majority of attention both in science and in the popular media, but RRBIs are equally important in understanding autism. Although RRBIs are also seen in typically developing preschoolers, as well as in other psychiatric disorders such as obsessive-compulsive disorder, their impairing and persisting character is a hallmark of ASD1.
Repetitive behaviors are among the first signs of ASD, with significant elevations by the child's first birthday2. Individuals with ASD of all ages and cognitive ability levels display RRBIs to variable degrees, with males usually being more severely affected than females3. Caregivers of individuals with ASD commonly emphasize that RRBIs are among the most challenging facets of the disorder on an everyday basis1. They negatively impact social, cognitive, family functioning and well-being, often leading to increased levels of parental stress and negative parenting styles. While the clinical description and natural history of RRBIs is becoming clear, an understanding of the biological bases of this set of features has only recently begun to emerge4. Better insight into the ontogenesis of RRBIs and their underlying neurobiology is needed not only to inform models of the etiology of ASD, but also to foster the development of new interventions.
In this issue of Biological Psychiatry, Langen et al.5 examine differences in the rate of basal ganglia growth in ASD relative to typically developing children (TDC). Their volumetric analyses focused on developmental trajectories of the ventral striatum (with nucleus accumbens) and dorsal striatum (with caudate nucleus and putamen). These components of the basal ganglia are the major subcortical targets within the frontostriatal behavior control loops that are recognized as likely subserving RRBIs4. This current study is a follow up of this same group's earlier work showing cross sectional differences in growth trajectory. While several labs have previously reported enlargement of the caudate nucleus in ASD, this current study is the first to make repeat morphology measurements, thus overcoming limitations associated with cross sectional analyses. This study involved 86 seven to seventeen year old cases and controls who had 2 MRI anatomical scans approximately 2 and a half years apart on average, allowing a direct test of differential striatal growth. The rate of basal ganglia growth was correlated with the severity of RRBIs as assessed by parent interview at the time of the first MRI scan, corroborating earlier work on the role of the striatum in repetitive behaviors among children with ASD.
Specifically the caudate nucleus showed a growth rate in ASD that was twice as high as the growth rate in TDC (i.e., 4.6% vs. 2.3%). This was independent of overall brain growth, use of psychotropic medications, or other major confounds. Most importantly, more severe RRBIs early in life, particularly insistence on sameness behaviors, such as avoiding trivial changes in routines and environments as well as adhering to compulsions and rituals, were related to faster striatal growth between average ages of about 9 and 12 year old, with large effect sizes (e.g., caudate nucleus: Cohen's d = 0.86). While Langen et al. discuss several complementary explanations for their findings, they conclude that the divergent trajectory of caudate development in relation to RRBIs most likely results from early, and possibly continuing, patterns of repetitive behaviors that shape striatal development – not the other way around.
This new set of data elegantly adds to the notion that the striatum plays a central role in core ASD phenomenology6. However, one question lingers: what cause RRBIs, like insistence on sameness, compulsions and rituals, to become such a force so as to impact the growth trajectory of an evolutionarily ancient brain structure like the caudate nucleus? This question ties in with a long-standing debate among clinicians and scientists concerning the potential functions that the myriad of RRBIs might serve in individuals with ASD. While several plausible ideas have been advanced7, convincing support for any specific one is lacking.
One hypothesis that is gaining increased research attention, however, involves the effects of alterations of the balance between social and nonsocial motivation in reward circuitry on RRBIs8. This model suggests that ASD is in part a disorder of "behavioral dependency" to RRBIs because of the rewarding effects they induce1. Indeed, insistence on sameness and preoccupying restricted interests are reported to be quite pleasurable by affected individuals1. The dorsal striatum with caudate nucleus, in particular, is believed to mediate reward value for purposeful actions5. Functional imaging studies show that the brain's reward circuitry in ASD, particularly striatum and ventral prefrontal cortices, selectively over-reacts to objects that may comprise an intense special interest, whereas it under-reacts to more typical desires such as social reward and money6. This may indicate that the brain in ASD cares less for conventional rewards. It is not yet known if an initial lack of social reward motivation opens the door for enhanced rewarding effects of certain circumscribed objects, topics, and routines, or whether the reverse is true – that the dominating reward effects of nonsocial objects, topic and routines diminishes the reward value of social engagement.
The rewarding effects of RRBIs are thought to be fueled by the preference of those with ASD for predictability in their environment, where they can exercise more control; social encounters are in many ways the antithesis of this, as these are often rapid, hard to control and offer much more variable reinforcement contingencies. When RRBIs are rewarding, their pursuit may be strengthened through reinforcement mechanisms that progressively turn them into rigid and strongly desired habits that are performed almost automatically with little conscious oversight. With this heuristic model, RRBIs are self-reinforcing, and they begin to hijack the normal developmental trajectory of entire repertoires of behaviors. The dorsal (associative) striatum with caudate nucleus dominates these processes4. Thus, an accelerated growth rate of the caudate related to RRBIs, as reported by Langen et al.5, could reflect atypical brain specialization in individuals with ASD9. From early in life the caudate nucleus mediates habitual processes for a wide range of different stimuli and contexts. Across development, however, the caudate may become co-opted by the most rewarding aspects of the environment. This interactive and self-sustaining biobehavioral process – in concert with other mesocorticolimbic functions4 – may shape the growth trajectory of the caudate nucleus and strengthens the occurrence of RRBIs in ASD (Figure 1). On a day-to-day basis, RRBIs interfere with social development and functioning as they may absorb resources typically dedicated to other learning opportunities, including social ones6.
The observation that RRBIs in ASD involve plasticity of the caudate nucleus – one major hub within the frontostriatal circuits that control behavior – is a fascinating advance for our field. It brings us closer to the neurobiological roots of how and why affected individuals develop and maintain this set of challenging behaviors. Follow-up research will need to address several issues to improve upon the approach of the Langen et al study. One critical issue is that researchers need to use more precise behavioral measurement tools10. This could involve item rating scales with greater item density around key concepts, as it is clear to all the ADI-R is sorely lacking in this regard. Also, quantitative motion capture tools are now widely available; deploying these in natural environments seems to us to be extremely promising adjuncts to standard rating scales. Repeat behavioral measurement across time, in sync with repeat brain measurement is an important next step that will enable better characterization of the interplay between RRBIs and brain dynamics. In this regard, multimodal imaging in the same sample is called for, as structural imaging will surely only capture portions of the story. The findings by Langen et al.5 call attention to the importance of RRBIs in autism. Because RRBIs may be rooted in the powerful reward circuitries that motivate a great deal of behavior, strategically targeting the role of reward mechanisms promises to improve treatment practices for limiting the life interfering aspects of RRBIs among individuals with ASD and their families.
Related Articles
In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in autism
Bernardi, Silvia
Anagnostou, Evdokia
Shen, Jun
Kolevzon, Alexander
Buxbaum, Joseph D.
Hollander, Eric
Hof, Patrick R.
Fan, Jin
Brain research
Attentional dysfunction is one of the most consistent findings in individuals with autism spectrum disorders (ASD). However, the significance of such findings for the pathophysiology of autism is unclear. In this study, we investigated cellular neurochemistry with proton magnetic resonance spectroscopy imaging (1H-MRS) in brain regions associated with networks subserving alerting, orienting, and executive control of attention in patients with ASD. Concentrations of cerebral N-acetyl-aspartate (NAA), creatinine + phosphocreatinine, choline-containing compounds, myo-inositol (Ins) and glutamate + glutamine (Glx) were determined by 3 T 1H-MRS examinations in 14 high-functioning medication-free adults with a diagnosis of ASD and 14 age- and IQ-matched healthy controls (HC) in the anterior cingulate cortex (ACC), thalamus, temporoparietal junction (TPJ), and areas near or along the intraparietal sulcus (IPS). Compared to HC group, the ASD group showed significantly lower Glx concentrations in right ACC and reduced Ins in left TPJ. This study provides evidence of abnormalities in neurotransmission related to networks subserving executive control and alerting of attention, functions which have been previously implicated in ASD pathogenesis.
autism; spectroscopy; glutamate; anterior cingulate cortex; intraparietal sulcus; myo-inositol
Related Articles
Functional and structural connectivity of frontostriatal circuitry in Autism Spectrum Disorder
Delmonte, Sonja
Gallagher, Louise
O'Hanlon, Erik
McGrath, Jane
Balsters, Joshua H.
Frontiers in Human Neuroscience
Abnormalities in frontostriatal circuitry potentially underlie the two core deficits in Autism Spectrum Disorder (ASD); social interaction and communication difficulties and restricted interests and repetitive behaviors. Whilst a few studies have examined connectivity within this circuitry in ASD, no previous study has examined both functional and structural connectivity within the same population. The present study provides the first exploration of both functional and structural frontostriatal connectivity in ASD. Twenty-eight right-handed Caucasian male ASD (17.28 ± 3.57 years) and 27 right-handed male, age and IQ matched controls (17.15 ± 3.64 years) took part in the study. Resting state functional connectivity was carried out on 21 ASD and control participants, and tractography was carried out on 22 ASD and 24 control participants, after excluding subjects for excessive motion and poor data quality. Functional connectivity analysis was carried out between the frontal cortex and striatum after which tractography was performed between regions that showed significant group differences in functional connectivity. The ASD group showed increased functional connectivity between regions in the frontal cortex [anterior cingulate cortex (ACC), middle frontal gyrus (MFG), paracingulate gyrus (Pcg) and orbitofrontal cortex (OFC)], and striatum [nucleus accumbens (NAcc) and caudate]. Increased functional connectivity between ACC and caudate was associated with deactivation to social rewards in the caudate, as previously reported in the same participants. Greater connectivity between the right MFG and caudate was associated with higher restricted interests and repetitive behaviors and connectivity between the bilateral Pcg and NAcc, and the right OFC and NAcc, was negatively associated with social and communicative deficits. Although tracts were reliably constructed for each subject, there were no group differences in structural connectivity. Results are in keeping with previously reported increased corticostriatal functional connectivity in ASD.
Autism Spectrum Disorder; connectivity; frontostriatal; striatum; fMRI; DTI; social reward
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Atypical Attentional Networks and the Emergence of Autism
Keehn, Brandon
Müller, Ralph-Axel
Townsend, Jeanne
Neuroscience and biobehavioral reviews
The sociocommunicative impairments that define autism spectrum disorder (ASD) are not present at birth but emerge gradually over the first two years of life. In typical development, basic attentional processes may provide a critical foundation for sociocommunicative abilities. Therefore early attentional dysfunction in ASD may result in atypical development of social communication. Prior research has demonstrated that persons with ASD exhibit early and lifelong impairments in attention. The primary aim of this paper is to provide a review of the extant research on attention in ASD using a framework of functionally independent attentional networks as conceptualized by Posner and colleagues: the alerting, orienting and executive control networks (Posner and Petersen, 1990; Petersen & Posner, 2012). The neural substrates and typical development of each attentional network is briefly discussed, a review of the ASD attention literature is presented, and a hypothesis is proposed that links aberrant attentional mechanisms, specifically impaired disengagement of attention, with the emergence of core ASD symptoms.
autism; attention; development; alerting; arousal; orienting; disengagement; executive control
Related Articles
Reduced cognitive control of response inhibition by the anterior cingulate cortex in autism spectrum disorders
Agam, Yigal
Joseph, Robert M.
Barton, Jason J.S.
Manoach, Dara S.
Response inhibition, or the suppression of prepotent, but contextually inappropriate behaviors, is essential to adaptive, flexible responding. In autism spectrum disorders (ASD), difficulty inhibiting prepotent behaviors may contribute to restricted, repetitive behavior (RRB). Individuals with ASD consistently show deficient response inhibition while performing antisaccades, which require one to inhibit the prepotent response of looking towards a suddenly appearing stimulus (i.e., a prosaccade), and to substitute a gaze in the opposite direction. Here, we used fMRI to identify the neural correlates of this deficit. We focused on two regions that are critical for saccadic inhibition: the frontal eye field (FEF), the key cortical region for generating volitional saccades, and the dorsal anterior cingulate cortex (dACC), which is thought to exert top-down control on FEF. We also compared ASD and control groups on the functional connectivity of the dACC and FEF during saccadic performance. In the context of an increased antisaccade error rate, ASD participants showed decreased functional connectivity of the FEF and dACC and decreased inhibition-related activation (based on the contrast of antisaccades and prosaccades) in both regions. Decreased dACC activation correlated with a higher error rate in both groups, consistent with a role in top-down control. Within the ASD group, increased FEF activation and dACC/FEF functional connectivity were associated with more severe RRB. These findings demonstrate functional abnormalities in a circuit critical for volitional ocular motor control in ASD that may contribute to deficient response inhibition and to RRB. More generally, our findings suggest reduced cognitive control over behavior by the dACC in ASD.
Related Articles
Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings
O'Dwyer, Laurence
Tanner, Colby
van Dongen, Eelco V.
Greven, Corina U.
Bralten, Janita
Zwiers, Marcel P.
Franke, Barbara
Heslenfeld, Dirk
Oosterlaan, Jaap
Hoekstra, Pieter J.
Hartman, Catharina A.
Groen, Wouter
Rommelse, Nanda
Buitelaar, Jan K.
PLoS ONE
Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups.
Related Articles
Abnormalities of Intrinsic Functional Connectivity in Autism Spectrum Disorders
Monk, Christopher S.
Peltier, Scott J.
Wiggins, Jillian Lee
Weng, Shih-Jen
Carrasco, Melisa
Risi, Susan
Lord, Catherine
Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
Related Articles
Language comprehension and brain function in individuals with an optimal outcome from autism
Eigsti, Inge-Marie
Stevens, Michael C.
Schultz, Robert T.
Barton, Marianne
Kelley, Elizabeth
Naigles, Letitia
Orinstein, Alyssa
Troyb, Eva
Fein, Deborah A.
NeuroImage : Clinical
Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23), OO (n = 16), or typical development (TD; n = 20) completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri) and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened "compensatory" activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus) and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development.
•fMRI study of "optimal outcome" (OO) youth with no symptoms of autism spectrum disorder.•Results show "compensatory" language activation in some areas in OO.•OO youth also had some "residual ASD" patterns of activation (OO, ASD > TD).•There was no evidence of areas of normalized brain function (OO, TD ≠ ASD).•Early treatment may normalize behavior but not brain in some individuals with ASD.
Autism; Optimal outcomes; Language; fMRI
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Mentalizing and motivation neural function during social interactions in autism spectrum disorders☆
Assaf, Michal
Hyatt, Christopher J.
Wong, Christina G.
Johnson, Matthew R.
Schultz, Robert T.
Hendler, Talma
Pearlson, Godfrey D.
NeuroImage : Clinical
Autism Spectrum Disorders (ASDs) are characterized by core deficits in social functions. Two theories have been suggested to explain these deficits: mind-blindness theory posits impaired mentalizing processes (i.e. decreased ability for establishing a representation of others' state of mind), while social motivation theory proposes that diminished reward value for social information leads to reduced social attention, social interactions, and social learning. Mentalizing and motivation are integral to typical social interactions, and neuroimaging evidence points to independent brain networks that support these processes in healthy individuals. However, the simultaneous function of these networks has not been explored in individuals with ASDs. We used a social, interactive fMRI task, the Domino game, to explore mentalizing- and motivation-related brain activation during a well-defined interval where participants respond to rewards or punishments (i.e. motivation) and concurrently process information about their opponent's potential next actions (i.e. mentalizing). Thirteen individuals with high-functioning ASDs, ages 12–24, and 14 healthy controls played fMRI Domino games against a computer-opponent and separately, what they were led to believe was a human-opponent. Results showed that while individuals with ASDs understood the game rules and played similarly to controls, they showed diminished neural activity during the human-opponent runs only (i.e. in a social context) in bilateral middle temporal gyrus (MTG) during mentalizing and right Nucleus Accumbens (NAcc) during reward-related motivation (Pcluster < 0.05 FWE). Importantly, deficits were not observed in these areas when playing against a computer-opponent or in areas related to motor and visual processes. These results demonstrate that while MTG and NAcc, which are critical structures in the mentalizing and motivation networks, respectively, activate normally in a non-social context, they fail to respond in an otherwise identical social context in ASD compared to controls. We discuss implications to both the mind-blindness and social motivation theories of ASD and the importance of social context in research and treatment protocols.
•We used an fMRI Domino game to map social networks in high-functioning ASDs.•ASDs did not show MTG increased activation during mentalizing in social context.•ASDs did not show NAcc increased activation for processing reward in social context.•Activation deficits were specific to brain areas involved in social processes.•Results support both the mind-blindness and the social motivation theories of ASDs.
Theory of mind; Reward; Nucleus accumbens; Middle temporal gyrus
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Redox metabolism abnormalities in autistic children associated with mitochondrial disease
Frye, R E
DeLaTorre, R
Taylor, H
Slattery, J
Melnyk, S
Chowdhury, N
James, S J
Translational Psychiatry
Research studies have uncovered several metabolic abnormalities associated with autism spectrum disorder (ASD), including mitochondrial disease (MD) and abnormal redox metabolism. Despite the close connection between mitochondrial dysfunction and oxidative stress, the relation between MD and oxidative stress in children with ASD has not been studied. Plasma markers of oxidative stress and measures of cognitive and language development and ASD behavior were obtained from 18 children diagnosed with ASD who met criteria for probable or definite MD per the Morava et al. criteria (ASD/MD) and 18 age and gender-matched ASD children without any biological markers or symptoms of MD (ASD/NoMD). Plasma measures of redox metabolism included reduced free glutathione (fGSH), oxidized glutathione (GSSG), the fGSH/GSSG ratio and 3-nitrotyrosine (3NT). In addition, a plasma measure of chronic immune activation, 3-chlorotyrosine (3CT), was also measured. Language was measured using the preschool language scale or the expressive one-word vocabulary test (depending on the age), adaptive behaviour was measured using the Vineland Adaptive Behavior Scale (VABS) and core autism symptoms were measured using the Autism Symptoms Questionnaire and the Social Responsiveness Scale. Children with ASD/MD were found to have lower scores on the communication and daily living skill subscales of the VABS despite having similar language and ASD symptoms. Children with ASD/MD demonstrated significantly higher levels of fGSH/GSSG and lower levels of GSSG as compared with children with ASD/NoMD, suggesting an overall more favourable glutathione redox status in the ASD/MD group. However, compare with controls, both ASD groups demonstrated lower fGSH and fGSH/GSSG, demonstrating that both groups suffer from redox abnormalities. Younger ASD/MD children had higher levels of 3CT than younger ASD/NoMD children because of an age-related effect in the ASD/MD group. Both ASD groups demonstrated significantly higher 3CT levels than control subjects, suggesting that chronic inflammation was present in both groups of children with ASD. Interestingly, 3NT was found to correlate positively with several measures of cognitive function, development and behavior for the ASD/MD group, but not the ASD/NoMD group, such that higher 3NT concentrations were associated with more favourable adaptive behaviour, language and ASD-related behavior. To determine whether difference in receiving medications and/or supplements could account for the differences in redox and inflammatory biomarkers across ASD groups, we examined differences in medication and supplements across groups and their effect of redox and inflammatory biomarkers. Overall, significantly more participants in the ASD/MD group were receiving folate, vitamin B12, carnitine, co-enzyme Q10, B vitamins and antioxidants. We then determined whether folate, carnitine, co-enzyme Q10, B vitamins and/or antioxidants influenced redox or inflammatory biomarkers. Antioxidant supplementation was associated with a significantly lower GSSG, whereas antioxidants, co-enzyme Q10 and B vitamins were associated with a higher fGSH/GSSG ratio. There was no relation between folate, carnitine, co-enzyme Q10, B vitamins and antioxidants with 3NT, 3CT or fGSH. Overall, our findings suggest that ASD/MD children with a more chronic oxidized microenvironment have better development. We interpret this finding in light of the fact that more active mitochondrial can create a greater oxidized microenvironment especially when dysfunctional. Thus, compensatory upregulation of mitochondria which are dysfunctional may both increase activity and function at the expense of a more oxidized microenvironment. Although more ASD/MD children were receiving certain supplements, the use of such supplements were not found to be related to the redox biomarkers that were related to cognitive development or behavior in the ASD/MD group but could possibly account for the difference in glutathione metabolism noted between groups. This study suggests that different subgroups of children with ASD have different redox abnormalities, which may arise from different sources. A better understanding of the relationship between mitochondrial dysfunction in ASD and oxidative stress, along with other factors that may contribute to oxidative stress, will be critical to understanding how to guide treatment and management of ASD children. This study also suggests that it is important to identify ASD/MD children as they may respond differently to specific treatments because of their specific metabolic profile.
autism; inflammation; endophenotypes; mitochondrial disease; oxidative stress
Related Articles
Impaired Error Monitoring and Correction Function in Autism
Sokhadze, Estate
Baruth, Joshua
El-Baz, Ayman
Horrell, Timothy
Sokhadze, Guela
Carroll, Thomas
Tasman, Allan
Sears, Lonnie
Casanova, Manuel F.
Journal of neurotherapy
Error monitoring and correction is one of the executive functions and is important for effective goal directed behavior. Deficient executive functioning, including reduced error monitoring ability, is one of the typical features of such neurodevelopmental disorders as autism, probably related to perseverative responding, stereotyped repetitive behaviors, and an inability to accurately monitor ongoing behavior. Our prior studies of behavioral and event-related potential (ERP) measures during performance on visual oddball tasks in high-functioning autistic (HFA) children showed that despite only minor differences in reaction times HFA children committed significantly more errors.
This study investigated error monitoring in children with autism spectrum disorder (ASD) with response-locked event-related potentials - the Error-related Negativity (ERN) and Error-related Positivity (Pe) recorded at fronto-central sites. The ERN reflects early error detection processes, while the Pe has been associated with later conscious error evaluation and attention re-allocation. Reaction times (RT) in correct trials and post-error slowing in reaction times were measured. In this study fourteen subjects with ASD and 14 age- and IQ- matched controls received a three-category visual oddball task with novel distracters.
ERN had a lower amplitude and longer latency in the ASD group but was localized in the caudal part of anterior cingulate cortex (ACC) in both groups. The Pe component was significantly prolonged in the ASD group but did not reach significance in amplitude differences compared to controls. We found significant post-error slowing in RTs in controls, and post-error acceleration in RTs in the ASD group.
The reduced ERN and altered Pe along with a lack of post-error RT slowing in autism might be interpreted as insensitivity in the detection and monitoring of response errors and a reduced ability of execute corrective actions. This might result in reduced error awareness and failure in adjustment when dealing with situations where erroneous responses may occur. This deficit might be manifested in the perseverative behaviors often seen in individuals with ASD. The results are discussed in terms of a general impairment in self-monitoring and other executive functions underlying behavioral and social disturbances in ASD.
Autism; Executive functions; Error monitoring; Reaction time; Cingulate cortex; oddball task
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Brain function and gaze-fixation during facial emotion processing in fragile-X and autism
Dalton, Kim M.
Holsen, Laura
Abbeduto, Leonard
Davidson, Richard J.
Autism research : official journal of the International Society for Autism Research
This research focuses on the relationship between fragile X syndrome (FXS) and autism spectrum disorders (ASD). Both of these populations have a tendency to avoid looking others in the eye, along with difficulties in communication with others and tend to be socially withdrawn. While it is clear that FXS and ASD share some common abnormal behaviors, the underlying brain mechanisms associated with the social and emotional deficits in these groups remain unclear. We showed pictures of emotional and non-emotional human faces to these groups while in a magnetic resonance scanner (MRI). We collected images of brain function along with measures of where on the faces the individuals were looking (e.g. eyes or mouth). The FXS group showed a similar yet less abnormal pattern of where they were looking on the face compared to the ASD group. The FXS group also showed a similar pattern of decreased brain function in the area of the brain typically used when looking at faces, the fusiform gyrus (FG). The amount of activation in the FG was associated with how much time the FXS and ASD individuals looked at the eyes, the more they looked at the eyes, the greater the FG activation. The FXS group also displayed more brain activation than both the ASD group and a group of typically developing control subjects in brain areas that might suggest increased task difficulty for the FXS group. These group differences in brain activation are important as they suggest there is some overlap in areas of brain function in FXS and ASD when looking at faces, but that these two groups also have unique activation in other brain areas. These findings largely support the idea that ASD characteristics in FXS are associated with partially different patterns of brain activation when looking at human faces compared to individuals with ASD.
Fragile X syndrome (FXS) is the most commonly known genetic disorder associated with autism spectrum disorder (ASD). Overlapping features in these populations include gaze aversion, communication deficits, and social withdrawal. Although the association between FXS and ASD has been well documented at the behavioral level, the underlying neural mechanisms associated with the social/emotional deficits in these groups remain unclear.
We collected functional brain images and eye-gaze fixations from 9 individuals with FXS and 14 individuals with idiopathic ASD, as well as 15 typically developing (TD) individuals, while they performed a facial-emotion discrimination task.
The FXS group showed a similar yet less aberrant pattern of gaze-fixations compared to the ASD group. The FXS group also showed fusiform gyrus (FG) hypoactivation compared to the TD control group. Activation in FG was strongly and positively associated with average eye fixation and negatively associated with ASD characteristics in the FXS group. The FXS group displayed significantly greater activation than both the TD control and ASD groups in the left hippocampus (HIPP), left superior temporal gyrus (STG), right insula (INS), and left post-central gyrus (PCG).
These group differences in brain activation are important as they suggest unique underlying face-processing neural circuitry in FXS versus idiopathic ASD, largely supporting the hypothesis that ASD characteristics in FXS and idiopathic ASD reflect partially divergent impairments at the neural level, at least in FXS individuals without a co-morbid diagnosis of ASD.
fragile X syndrome; autism; face processing; brain function; fMRI
Related Articles
Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome
Wang, A. Ting
Lim, Teresa
Jamison, Jesslyn
Bush, Lauren
Soorya, Latha V.
Tavassoli, Teresa
Siper, Paige M.
Buxbaum, Joseph D.
Kolevzon, Alexander
Journal of Neurodevelopmental Disorders
Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS. No controlled neuroimaging studies of PMS have been reported to date. The goal of this study was to examine the neural circuitry supporting the perception of auditory communicative signals in children with PMS as compared to idiopathic ASD (iASD).
Eleven children with PMS and nine comparison children with iASD were scanned using functional magnetic resonance imaging (fMRI) under light sedation. The fMRI paradigm was a previously validated passive auditory task, which presented communicative (e.g., speech, sounds of agreement, disgust) and non-communicative vocalizations (e.g., sneezing, coughing, yawning).
Previous research has shown that the superior temporal gyrus (STG) responds selectively to communicative vocal signals in typically developing children and adults. Here, selective activity for communicative relative to non-communicative vocalizations was detected in the right STG in the PMS group, but not in the iASD group. The PMS group also showed preferential activity for communicative vocalizations in a range of other brain regions associated with social cognition, such as the medial prefrontal cortex (MPFC), insula, and inferior frontal gyrus. Interestingly, better orienting toward social sounds was positively correlated with selective activity in the STG and other "social brain" regions, including the MPFC, in the PMS group. Finally, selective MPFC activity for communicative sounds was associated with receptive language level in the PMS group and expressive language in the iASD group.
Despite shared behavioral features, children with PMS differed from children with iASD in their neural response to communicative vocal sounds and showed relative strengths in this area. Furthermore, the relationship between clinical characteristics and neural selectivity also differed between the two groups, suggesting that shared ASD features may partially reflect different neurofunctional abnormalities due to differing etiologies.
Electronic supplementary material
The online version of this article (doi:10.1186/s11689-016-9138-9) contains supplementary material, which is available to authorized users.
Related Articles
The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders
Solomon, Marjorie
Ozonoff, Sally
Ursu, Stefan
Ravizza, Susan
Cummings, Neil
Ly, Stanford
Carter, Cameron
Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms.
autism spectrum disorders; cognitive control; executive functions; fMRI; functional connectivity; attention deficit disorder
Related Articles
Alterations of Resting State Functional Connectivity in the Default Network in Adolescents with Autism Spectrum Disorders
Weng, Shih-Jen
Wiggins, Jillian Lee
Peltier, Scott J.
Carrasco, Melisa
Risi, Susan
Lord, Catherine
Monk, Christopher S.
Brain research
Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a cognitive task, but also exists in the absence of a task (i.e., "rest"). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.
Functional Magnetic Resonance Imaging; development; symptom severity; Asperger's syndrome; pervasive developmental disorder not otherwise specified
Related Articles
Atypical Neural Networks for Social Orienting in Autism Spectrum Disorders
Greene, Deanna J.
Colich, Natalie
Iacoboni, Marco
Zaidel, Eran
Bookheimer, Susan Y.
Dapretto, Mirella
Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.
autism; attention; functional magnetic resonance imaging; gaze; social cue
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NTRK2 expression levels are reduced in laser captured pyramidal neurons from the anterior cingulate cortex in males with autism spectrum disorder
Chandley, Michelle J
Crawford, Jessica D
Szebeni, Attila
Szebeni, Katalin
Ordway, Gregory A
Molecular Autism
The anterior cingulate cortex (ACC) is a brain area involved in modulating behavior associated with social interaction, disruption of which is a core feature of autism spectrum disorder (ASD). Functional brain imaging studies demonstrate abnormalities of the ACC in ASD as compared to typically developing control patients. However, little is known regarding the cellular basis of these functional deficits in ASD. Pyramidal neurons in the ACC are excitatory glutamatergic neurons and key cellular mediators of the neural output of the ACC. This study was designed to investigate the potential role of ACC pyramidal neurons in ASD brain pathology.
Postmortem ACC tissue from carefully matched ASD and typically developing control donors was obtained from two national brain collections. Pyramidal neurons and surrounding astrocytes were separately collected from layer III of the ACC by laser capture microdissection. Isolated RNA was subjected to reverse transcription and endpoint PCR to determine gene expression levels for 16 synaptic genes relevant to glutamatergic neurotransmission. Cells were also collected from the prefrontal cortex (Brodmann area 10) to examine those genes demonstrating differences in expression in the ACC comparing typically developing and ASD donors.
The level of NTRK2 expression was robustly and significantly lower in pyramidal neurons from ASD donors as compared to typically developing donors. Levels of expression of GRIN1, GRM8, SLC1A1, and GRIP1 were modestly lower in pyramidal neurons from ASD donors, but statistical significance for these latter genes did not survive correction for multiple comparisons. No significant expression differences of any genes were found in astrocytes laser captured from the same neocortical area. In addition, expression levels of NTRK2 and other synaptic genes were normal in pyramidal neurons laser captured from the prefrontal cortex.
These studies demonstrate a unique pathology of neocortical pyramidal neurons of the ACC in ASD. NTRK2 encodes the tropomyosin receptor kinase B (TrkB), transmission through which neurotrophic factors modify differentiation, plasticity, and synaptic transmission. Reduced pyramidal neuron NTRK2 expression in the ACC could thereby contribute to abnormal neuronal activity and disrupt social behavior mediated by this brain region.
Electronic supplementary material
The online version of this article (doi:10.1186/s13229-015-0023-2) contains supplementary material, which is available to authorized users.
Pyramidal neurons; Astrocytes; Cingulate; Autism; Glutamate receptors
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Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates
Barendse, Evelien M
Hendriks, Marc PH
Jansen, Jacobus FA
Backes, Walter H
Hofman, Paul AM
Thoonen, Geert
Kessels, Roy PC
Aldenkamp, Albert P
Journal of Neurodevelopmental Disorders
Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.
Working memory; Adolescents; Autism; Neuropsychology; Neuroimaging
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The brains of high functioning autistic individuals do not synchronize with those of others☆
Salmi, J.
Roine, U.
Glerean, E.
Lahnakoski, J.
Nieminen-von Wendt, T.
Tani, P.
Leppämäki, S.
Nummenmaa, L.
Jääskeläinen, I.P.
Carlson, S.
Rintahaka, P.
Sams, M.
NeuroImage : Clinical
Multifaceted and idiosyncratic aberrancies in social cognition characterize autism spectrum disorders (ASDs). To advance understanding of underlying neural mechanisms, we measured brain hemodynamic activity with functional magnetic resonance imaging (fMRI) in individuals with ASD and matched-pair neurotypical (NT) controls while they were viewing a feature film portraying social interactions. Pearson's correlation coefficient was used as a measure of voxelwise similarity of brain activity (InterSubject Correlations—ISCs). Individuals with ASD showed lower ISC than NT controls in brain regions implicated in processing social information including the insula, posterior and anterior cingulate cortex, caudate nucleus, precuneus, lateral occipital cortex, and supramarginal gyrus. Curiously, also within NT group, autism-quotient scores predicted ISC in overlapping areas, including, e.g., supramarginal gyrus and precuneus. In ASD participants, functional connectivity was decreased between the frontal pole and the superior frontal gyrus, angular gyrus, superior parietal lobule, precentral gyrus, precuneus, and anterior/posterior cingulate gyrus. Taken together these results suggest that ISC and functional connectivity measure distinct features of atypical brain function in high-functioning autistic individuals during free viewing of acted social interactions. Our ISC results suggest that the minds of ASD individuals do not 'tick together' with others while perceiving identical dynamic social interactions.
•We studied brain function in autism during free viewing of social interactions.•The brains of individuals with autism do not 'tick together' with others.•Long-range functional connectivity is altered in individuals with autism.•Link between autistic traits and social brain synchrony extends to normal population.
Asperger syndrome; fMRI; Intersubject correlation; Movie; Social brain
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Caudate Nucleus Volume and Cognitive Performance: Are they related in Childhood Psychopathology?1
Voelbel, Gerald T.
Bates, Marsha E.
Buckman, Jennifer F.
Pandina, Gahan
Hendren, Robert L.
Biological psychiatry
Impaired neuropsychological test performance, especially on tests of executive function and attention, is often seen in children diagnosed with autism spectrum disorders (ASD). Structures involved in fronto-striatal circuitry, such as the caudate nucleus, may support these cognitive abilities. However, few studies have examined caudate volumes specifically in children with ASD, or correlated caudate volumes to cognitive ability.
Neuropsychological test scores and caudate volumes of children with ASD were compared to those of children with bipolar disorder (BD) and of typically developing (TD) children. The relationship between test performance and caudate volumes was analyzed.
The ASD group displayed larger right and left caudate volumes, and modest executive deficits, compared to TD controls. While caudate volume inversely predicted performance on the Wisconsin Card Sorting Test in all participants, it differentially predicted performance on measures of attention across the ASD, BD and TD groups.
Larger caudate volumes were related to impaired problem solving. On a test of attention, larger left caudate volumes predicted increased impulsivity and more omission errors in the ASD group as compared to the TD group, however smaller volume predicted poorer discriminant responding as compared to the BD group.
executive function; attention; bipolar disorder; autism spectrum disorders; caudate volume; neuroimaging
Related Articles
Sokhadze, Estate M.
Baruth, Joshua M.
Sears, Lonnie
Sokhadze, Guela E.
El-Baz, Ayman S.
Williams, Emily
Klapheke, Robert
Casanova, Manuel F.
Journal of neurotherapy
Autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD) are very common developmental disorders which share some similar symptoms of social, emotional, and attentional deficits. This study is aimed to help understand the differences and similarities of these deficits using analysis of dense-array event-related potentials (ERP) during an illusory figure recognition task. Although ADHD and ASD seem very distinct, they have been shown to share some similarities in their symptoms. Our hypothesis was that children with ASD will show less pronounced differences in ERP responses to target and non-target stimuli as compared to typical children, and to a lesser extent, ADHD. Participants were children with ASD (N=16), ADHD (N=16), and controls (N=16). EEG was collected using a 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. There were no between group differences in reaction time (RT) to target stimuli, but both ASD and ADHD committed more errors, specifically the ASD group had statistically higher commission error rate than controls. Post-error RT in ASD group was exhibited in a post-error speeding rather than corrective RT slowing typical for the controls. The ASD group also demonstrated an attenuated error-related negativity (ERN) as compared to ADHD and controls. The fronto-central P200, N200, and P300 were enhanced and less differentiated in response to target and non-target figures in the ASD group. The same ERP components were marked by more prolonged latencies in the ADHD group as compared to both ASD and typical controls. The findings are interpreted according to the "minicolumnar" hypothesis proposing existence of neuropathological differences in ASD and ADHD, specifically minicolumnar number/width morphometry spectrum differences. In autism, a model of local hyperconnectivity and long-range hypoconnectivity explains many of the behavioral and cognitive deficits present in the condition, while the inverse arrangement of local hypoconnectivity and long-range hyperconnectivity in ADHD explains some deficits typical for this disorder. The current ERP study supports the proposed suggestion that some between group differences could be manifested in the frontal ERP indices of executive functions during performance on an illusory figure categorization task.
Autism Spectrum Disorder; ADHD; Event-related Potential; Attention
Related Articles
fMRI evidence of neural abnormalities in the subcortical face processing system in ASD
Kleinhans, Natalia M.
Richards, Todd
Johnson, L. Clark
Weaver, Kurt E.
Greenson, Jessica
Dawson, Geraldine
Aylward, Elizabeth
Recent evidence suggests that a rapid, automatic face-detection system is supported by subcortical structures including the amygdala, pulvinar, and superior colliculus. Early emerging abnormalities in these structures may be related to reduced social orienting in children with autism, and subsequently, to aberrant development of cortical circuits involved in face processing. Our objective was to determine whether functional abnormalities in the subcortical face processing system are present in adults with autism spectrum disorders (ASD) during supraliminal fearful face processing. Participants included twenty-eight individuals with ASD and 25 controls group-matched on age, IQ, and behavioral performance. The ASD group met diagnostic criteria on the ADI-R, ADOS-G, and DSM-IV. Both the ASD and control groups showed significant activation in bilateral fusiform gyri. The control group exhibited additional significant responses in the right amygdala, right pulvinar, and bilateral superior colliculi. In the direct group comparison, the controls showed significantly greater activation in the left amygdala, bilateral fusiform gyrus, right pulvinar, and bilateral superior colliculi. No brain region showed significantly greater activation in the ASD group compared to the controls. Thus, basic rapid face identification mechanisms appear to be functional in ASD. However, individuals with ASD failed to engage the subcortical brain regions involved in face detection and automatic emotional face processing, suggesting a core mechanism for impaired socioemotional processing in ASD. Neural abnormalities in this system may contribute to early emerging deficits in social orienting and attention, the putative precursors to abnormalities in social cognition and cortical face processing specialization.
Related Articles
Autism is characterized by dorsal anterior cingulate hyperactivation during social target detection
Dichter, Gabriel S.
Felder, Jennifer N.
Bodfish, James W.
Social Cognitive and Affective Neuroscience
Though the functional neural correlates of impaired cognitive control and social dysfunction in autism spectrum disorders (ASD) have been delineated, brain regions implicated in poor cognitive control of social information is a novel area of autism research. We recently reported in a non-clinical sample that detection of 'social oddball' targets activated a portion of the dorsal anterior cingulate gyrus and the supracalcarine cortex (Dichter, Felder, Bodfish, Sikich, and Belger, 2009). In the present investigation, we report functional magnetic resonance imaging results from individuals with ASD who completed the same social oddball task. Between-group comparisons revealed generally greater activation in the ASD group to both social and non-social targets. When responses to social and non-social targets were contrasted, the ASD group showed relatively greater activation in the right and middle inferior frontal gyri and a region in dorsomedial prefrontal cortex that abuts the dorsal anterior cingulate (Brodmann's Area 32). Further, dorsal anterior cingulate activation to social targets predicted the severity of social impairments in a subset of the ASD sample. These data suggest that the dorsal anterior cingulate mediates social target detection in neurotypical individuals and is implicated in deficits of cognitive control of social information in ASD.
autism; fMRI; target detection; face processing; cingulate gyrus
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Chocolate Power Balls
Total Time
Prep 10 mins
Cook 15 mins
These are a delicious after-gym snack with a good hit of protein, and of course chocolate! Adapted from http://spabettie.com/2012/04/13/double-rich-chocolate-protein-cookie/
Ingredients Nutrition
- 1 (19 ounce) can chickpeas, drained and rinsed shopping list
- 1⁄4 cup unsweetened almond milk
- 6 tablespoons chocolate protein powder (I used Vega One Nutritional Shake)
- 2 (1 g) packets stevia
- 3⁄4 cup dark semisweet chocolate chunk (I used stevia-sweetened CocoPolo)
- In food processor or blender, puree chickpeas, almond milk, protein powder and stevia.
- Process to form a dough ball.
- Fold in chocolate chunks, then roll into 1-inch balls. Bake at 350 for 12-15 minutes.


text:
9 posts tagged with nathanrabin.
Displaying 1 through 9 of 9. Subscribe:
The Least Essential Albums of 2015
The (Onion) A. V. Club continues its annual tradition by announcing the least essential albums of the year. While many of them are bad, the purpose is not to highlight the most awful music but the music which has the flimsiest justification for being made. [more inside]
"It never ... Not even once ... ever works"
Cameron Crowe's new movie Aloha got its first bad review when Amy Pascal's emails were hacked. "I'm never starting a movie again when the script is ridiculous," she wrote. "I don't care how much I love the director and the actors." This was before anyone got wind that this was the latest of in long, disgraceful history of movies set in Hawaii that erase POC from a location where the population is only around 30% Caucasian. But as Jen Yamoto points out in The Daily Beast, "Aloha actually features one of the more prominent Asian/mixed heritage female leads in any studio movie in recent memory. She just happens to be played by Emma Stone." [more inside]
American business is about to go... into the RED
The Dissolve's Nathan Rabin kicks off One and Done - a look at writers, directors and actors who only made a significant contribution to a single film - with a dive into Carrot Top's Chairman of the Board.
Cribbing from Pee Wee's Big Adventure and Yahoo Serious, this 1998 opus failed to establish the college prop comic as a box office draw. However, the appearance of Chairman of the Board co-star Courtney Thorne-Smith on Conan O'Brien (with guest Norm MacDonald) is unforgettable.
Cribbing from Pee Wee's Big Adventure and Yahoo Serious, this 1998 opus failed to establish the college prop comic as a box office draw. However, the appearance of Chairman of the Board co-star Courtney Thorne-Smith on Conan O'Brien (with guest Norm MacDonald) is unforgettable.
Days of Thunder
"Days Of Thunder's script wasn't complete when shooting started, and Towne reportedly wrote and re-wrote many scenes on the day of filming, which helps explain why a script by a man widely considered one of the greatest screenwriters of all time is filled with rookie mistakes. It's chockablock with moments where characters tell other characters things they both obviously know, solely for the benefit of an unseen audience. Also, it's utter garbage." Nathan Rabin reexamines 1990's 13th biggest movie in The Dissolve's ongoing Forgotbusters series. List of previous Forgotbusters here.
"Would you want to be in a group with Criss and Frehley?"
Nathan Rabin reviews the Kiss autobiographies for the A.V. Club. The memoir of Kiss drummer Peter Criss is endearingly needy and sleazy: "Makeup To Breakup positively vibrates with rage toward Criss' former bandmates, Kiss' management, and everything Kiss represents." Gene Simmons' Kiss And Make-Up lets The Demon speak for himself: "To critics who ask how he could have treated core members of his group so coldly, he responds, "Would you want to be in a group with Criss and Frehley?"" Spaceman Ace Frehley offers his bland version of Kiss' story in No Regrets: "For better or worse, No Regrets, Frehley's curiously underwhelming 2011 memoir, is the product of an author who can also now assure himself that no matter how debauched or crazy he might get, at least he isn't Ace Frehley-in-the-'70s-level debauched or crazy."
LOL Cat!?!
"Joy is the antithesis of sneering cynicism . . . I've come to love country in part because it's such a potent vessel for expressing joy."
Nashville or Bust is a project where the Onion A.V. Club's Nathan Rabin (previously), who has predominantly listened to hip-hop in the past, spent a year listening to country music. The series proper (apart from a planned road trip in February) ended yesterday with a thoughtful essay about Charley Pride. Along the way the author wrote about Johnny Cash's "Christianity . . . of the deeply spiritual, non-commercial, almost creepily intimate variety," discovered that Willie Nelson "is the coolest motherfucker on the planet," had a hard time imagining Merle Haggard living on a houseboat, decided Garth Brooks is not history's greatest monster, and found the Dixie Chicks to be "way more badass than Toby Keith."
KFC Double Down
"God clearly did not mean for humans to eat chicken, bacon, and low-quality, gelatinous cheese at the same time." Nathan Rabin tackles KFC's Double Down combo.
The Year of Flops
On Tuesday, A.V. Club critic Nathan Rabin's reassessment of the rabidly ambitious Perfume: The Story of a Murderer marked the culmination of his Year of Flops project, a reviewing marathon of 104 commercial and critical failures. Here's the index of the films, sorted into Elizabethtown-derived categories of good but luckless movies, ordinary losers, and disasters of mythic proportions. [more inside]
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By working alongside you, the client, giving practical business advice and support, we ensure that you achieve your goals and make your business more successful.
Ours is a very hands-on approach, providing you with the information, tools and advice to enable you to focus on your key issues and manage your business to its maximum in the most cost-effective way.
We work in enterprises of every size, but concentrate on the small and medium sector. Owners of such companies express concerns about their lack of skills, experience and time. This inhibits not only the ongoing, day-to-day management, but just as vital, pursuing and achieving growth.
Tailored Solutions
Every business is unique and we offer solutions that are tailored to you, your company and your culture, whether you are at an early stage, or an established company looking at rapid expansion.
The principals of Nigel Wild Associates have a pedigree of successful delivery in UK, Europe, the Far East and North America across a range of disciplines, but specialise in Human Resources, Public Relations and Biotechnology. Through the Business Support Programme, they can call upon top-class experts in almost any discipline.
Oxfordshire Chamber of Commerce
As President of Oxfordshire Chamber of Commerce, Nigel Wild is at the very heart of businesses large and small, understanding their needs and campaigning for measures to improve the business climate in the Thames Valley.
Business Support
Nigel Wild, Managing Director of Nigel Wild Associates, is an Accredited Associate of the Institute for Independent Business.
The Institute was founded in 1984. It is a not-for-profit training and accreditation organisation, estabished to fulfil a hitherto unmet need for practical advice and support to small and medium size businesses, the SMEs. This is achieved by providing access to top-flight business experts who have been trained and accredited in advising SMEs.
The Business Support Programme has been devised to cater for the needs of managing directors and owners for independent advice and support. Its key strength is the huge network of over 4,000 Associates worldwide, whose expertise in specialist areas can be utilised within the Programme at significantly reduced rates.
We work in and with your business, calling upon the services of our fellow Associates as required. This gives you not only the same resources as much larger corporations, but allows you to compete effectively with them at a fraction of the cost you would expect to pay for this kind of expertise and breadth of experience.
There is a truly amazing amount of 'horsepower' and knowhow in the Associate network, covering almost any issue likely to be encountered.
Under the Business Support Programme (BSP), you will be allocated a number of days per month, typically 2 days or more, for the exact advice and support you need for your business.
The process begins with an initial meeting which is totally free of charge and without obligation. It offers you the opportunity to discuss your business and any issues you may face in complete confidence. To gain the most benefit from the meeting, it is best that all owners, partners or directors participate. This meeting usually takes around two hours.
There is no formal presentation, no hard sell, just your chance to talk about your operations with an experienced business executive.
To find out more about the Institute for Independent Business, please click on www.iib.org.ws
Human Resources
Human Resources are a vital issue for any organisation, but none more so than today. Attracting, motivating and retaining skilled, experienced staff in the current labour market place huge demands on the company. The increasing complexity of law and regulation makes still further demands. Few SMEs have the expertise or resources to handle their personnel management effectively.
We do have that expertise and can offer you an outsourced HR Department with over 30 years UK and international experience, up-to-date knowledge of UK Employment Law and backed by the unrivalled resources of the Chartered Institute of Personnel and Development.
We act as the virtual HR director and virtual HR department for a wide range of organisations large and small, advising, guiding and mentoring on people issues. Our emphasis is always on good people management, giving confidence to our clients to address staffing matters proactively and effectively. Ignoring any problems that may arise will not make them go away – they will just get worse.
"I act as interim Finance Director for companies. Nigel provides HR support and guidance to a number of my clients. An excellent, highly professional service."
Interim Finance Director
"We are delighted with the service you provide."
Managing Director Sales and Marketing Company
Public Relations and Business Writing
Nigel Wild is also a freelance journalist and author, contributing regular columns to newspapers and experienced in handling the media.
Public relations need to be part of your business. A punchy, well-written and targeted press release can be a powerful tool in gaining you fresh business and enhancing your reputation in the marketplace. And it's all free publicity!
Or perhaps your website needs writing or revising. Far too many websites are dull and peppered with spelling and grammatical errors, giving entirely the wrong message.
Get the right message across with a sharp, creative webscript and gain more customers.
"Thank you for the copy, it reads very well indeed. It gets all the points across and we will be able to use it for at least 10 years. Not only have you done it well, you have also done it very quickly."
Managing Director Construction Company
"You have a real knack for getting to the heart of things and getting them right. I have worked with a lot of journalists who don't."
CEO Life Sciences Company
Email firstname.lastname@example.com for a free copy of our guide 'Enhancing your business through successful public relations'
Since 1990, Nigel Wild has been actively involved in biotechnology, bioincubation and pharmaceuticals across the globe.
- Pharmaceuticals
He was a founder member of the first overseas research facility for Japanese pharmaceutical major Yamanouchi in Oxford, taking it from greenfield site to award winner.
- Incubation
Nigel masterminded the establishment of a biotechnology incubator, the Oxford BioBusiness Centre, and became its Managing Director in 2002. He has invaluable expertise in working with SMEs and startups and helping them to commercialise their ideas. In 2003, the incubator won the global award 'Best Science Based Incubator'.
He managed the highly acclaimed EU project Biolink, combining the strengths of incubators across Europe to fast-track bioincubation.
- UK BiotechNet
UK BiotechNet is a consortium of biotechnology professionals with complementary experience providing appropriate, professional, discrete, expert services to clients. Nigel was a founding member, devoting much time and energy to improving and enlarging skills and knowledge in the sector. www.biotechnet.co.uk
- Journalism
His monthly feature Bioline in Oxfordshire's newspaper, the Oxford Times, showcases life science companies in the region's cluster and has become a must-read in the scientific and business communities. www.oxfordtimes.co.uk/business/profiles/bioline
- Biotechnology Facilities
Currently, he is a UK-based member of a team that has built and is now managing Saudi Arabia's first biotech incubator. Called Badir for Biotechnology, it is located in the Faculty of Medicine of Riyadh's largest hospital. With real expertise in designing, constructing and managing biotechnology facilities, Nigel was solely responsible for this phase of the project. The client is delighted with this state-of-the-art and much admired facility. www.badirbio.com
At the 2010 Best Practice in Science Based Incubators conference in Liverpool, Nigel arranged for the head of the Badir incubators programme, Dr Abdulaziz Al Hargan, to present on incubation in the Kingdom. www.technopolicy.net


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Lange Jan Hotel
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Travel Blogs from Amersfoort
Last day of WAO
... being played for the winner of each height.
After that had finished, I had to take my bike back to Udell. I have loved having that because it was very quick to go back to our accommodation during the day to charge up devices etc and I had my lovely ride on Friday. Til came and picked me up, and we managed to fit the bags in the car again. It was great having a car available, but it was pretty tiny.
Til had been in contact with a lady from ...
Sin City - Welcome to Amsterdam
... place was the Anne Frank Huis. Very touching to read her story and be in the very house where her family had to hide. It's so saddening to know she had to live through that horrible time and experience the world like that at such a young age.
We spent the last of our day relaxing by the canals and had a sushi feast for dinner before heading back to the UK. Overall a beautiful city that I'd love to visit again when the tulips are in full bloom!!!
Much love,
Train to Amsterdam
... the museum.
Lots of push bikes around, even with the light rain. Didn't realise they have their own push bike lane on the road which I was walking down thinking it was the edge of the road and ended up getting belled at by some bike riders for walking in their lane. You have to watch out here for cars and push bikes when you cross the road!
Day tour of Amsterdam ...
Amsterdam day 2
Having slept in the tiny bed we asked if there were any rooms with king beds and got lucky with a lovely quiet room. All the dutch people we met our whole trip were lovely - friendly, helpful and accommodating and of course all spoke perfect english. A bit different to berlin!
After breakfast we visited the Best friends 2 coffee shop to sample some of the local ...
Back to Amsterdam
... from the hustle and bustle in the streets around it. Taking advantage of a break in the rain we wandered back over to Anne Frank Huis hoping the line up would be smaller in the evening, and luckily it was so after about 25 minutes we were able to enter. The Anne Frank Huis was another very moving experience and had inspired me to read the book. Amy has read the book and she now has greater appreciation of the conditions Anne and her family ...


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With over 300,000 lightning strikes in the UK every year, organisations should have a lightning protection system installed to protect their building, its occupants and contents from potential damage in the event of a strike.
The majority of buildings will be termed a 'critical structure' as defined in the recognised British Standard for the design, installation and testing of lightning protection systems, BS EN 62305:2011 (part 3), and will require an annual test and inspection programme undertaken by a competent Specialist Contractor to ensure their continued safety to protect the building.
ATLAS is aware that there are an increasing number of companies who are not qualified or competent to undertake this specialist work and launched its Inspect and Protect Campaign to raise quality standards for the testing and inspection of lightning protection systems.
What is a Critical Structure?
A critical structure is defined as one which contains sensitive internal systems including office blocks; commercial buildings or places where a high number of people may be present, such as churches or heritage buildings; and buildings where explosive materials are stored. Buildings which are classed as 'critical' should have their lightning protection system visually inspected every six months with electrical testing performed once a year.
Annual Testing
Electrical testing should be undertaken every year by a competent person who has the training and experience of working within the lightning protection industry. ATLAS recommends that clients use the services of a Specialist Contractor which has the knowledge and skills to test and inspect the system in line with its design and installation.
Additional testing will also be required to the lightning protection system after any building remedial works have taken place.
ATLAS Campaign
The Inspect and Protect Campaign from ATLAS has two key objectives:
- Establish clear standards of competency for testing and inspection work
This includes the promotion of formal qualifications, ensuring clients use reputable companies with a track record of lightning protection work and receive a formal outline of the work to be undertaken.
- Encourage clients to specify ATLAS members for testing and inspection work
To help you to identify an experienced lightning protection professional, ATLAS has developed the handy leaflet Choosing a Specialist Contractor for your Lightning Protection System outlining the skills and experience that you should look for when choosing your Specialist Contractor. Use this in conjunction with the Client Checklist for Lightning Protection Systems to ensure that the Specialist Contractor is able to provide a thorough inspection of your system in line with the current British Standard.
For more information or to contact an ATLAS member, visit the Find a Member page.


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It was a wave that could have cost a Dunedin man his life.
Rueben Skipper was bodyboarding barrel after barrel at Aramoana last Thursday afternoon when suddenly "there was no more water - just sand".
"It was like jumping off a roof and landing straight on your bum," the 40-year-old said from his bed in Dunedin Hospital yesterday.
He hit the sand so hard he heard the crunching sound of his own spine. He was pulled back into the water by the waves and tried to get the attention of fellow bodyboarder Stuart Barson.
Mr Skipper, who was screaming and trying not to vomit, was pulled towards the shallows by his mate, who signalled for a man on a jet ski to help him take Mr Skipper to the beach.
Although Mr Skipper feared the worst, fate suddenly took a strange twist.
"I see this lady walking her dog coming up and it turns out she was a doctor from the hospital's intensive care unit."
She was able to call emergency services to the scene while assisting Mr Skipper, who was "just lying in the wetsuit shaking and moaning".
He was so cold paramedics could not get pain relief into his veins, and he was later taken by the Otago Regional Rescue Helicopter to hospital.
He was diagnosed with a shattered vertebra and spent his first five days "lying on my back even unable to cross my legs".
"I might still be getting surgery, but hopefully not," the father of three said.
Mr Skipper, who works at the Upstart Business Incubator and also runs a two-month-old start-up company, Swift Social, specialising in social media management for small businesses, said he had been amazed by the support.
He acknowledged that he was "very lucky" receiving the support he did that day.
"I could have been paralysed; I could have been dead."


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GDE Admissions
The MA in Global Development Economics is administered by the Economics Department. Admissions and all other administrative matters are handled by that department. The Economics Department is a component of the Graduate School of Arts & Sciences (GRS). General information on applying to GRS can be found here. Specific information on applying to the Economics Department can be found here.
Applications should be submitted by March 1. The GDE program does not accept Spring Semester applications. All application materials must be received by the application deadline. Admission decisions are made by a faculty committee.
All questions about the GDE can be directed the Economics Department staff. Contact information can be found here.
Boston University's policies provide for equal opportunity and affirmative action in employment and admission to all programs of the University.