Although rises in cortisol can benefit memory consolidation, as can sleep soon after encoding, there is currently a paucity of literature as to how these two factors may interact to influence consolidation. Here we present a protocol to examine the interactive influence of cortisol and sleep on memory consolidation, by combining three methods: eye tracking, salivary cortisol analysis, and behavioral memory testing across sleep and wake delays. To assess resting cortisol levels, participants gave a saliva sample before viewing negative and neutral objects within scenes. To measure overt attention, participants’ eye gaze was tracked during encoding. To manipulate whether sleep occurred during the consolidation window, participants either encoded scenes in the evening, slept overnight, and took a recognition test the next morning, or encoded scenes in the morning and remained awake during a comparably long retention interval. Additional control groups were tested after a 20 min delay in the morning or evening, to control for time-of-day effects. Together, results showed that there is a direct relation between resting cortisol at encoding and subsequent memory, only following a period of sleep. Through eye tracking, it was further determined that for negative stimuli, this beneficial effect of cortisol on subsequent memory may be due to cortisol strengthening the relation between where participants look during encoding and what they are later able to remember. Overall, results obtained by a combination of these methods uncovered an interactive effect of sleep and cortisol on memory consolidation.
25 Related JoVE Articles!
Low-stress Route Learning Using the Lashley III Maze in Mice
Institutions: Pennsylvania State University, Pennsylvania State University, Pennsylvania State University, Pennsylvania State University, University of California, Los Angeles, University of California, Los Angeles.
Many behavior tests designed to assess learning and memory in rodents, particularly mice, rely on visual cues, food and/or water deprivation, or other aversive stimuli to motivate task acquisition. As animals age, sensory modalities deteriorate. For example, many strains of mice develop hearing deficits or cataracts. Changes in the sensory systems required to guide mice during task acquisition present potential confounds in interpreting learning changes in aging animals. Moreover, the use of aversive stimuli to motivate animals to learn tasks is potentially confounding when comparing mice with differential sensitivities to stress. To minimize these types of confounding effects, we have implemented a modified version of the Lashley III maze. This maze relies on route learning, whereby mice learn to navigate a maze via repeated exposure under low stress conditions, e.g. dark phase, no food/water deprivation, until they navigate a path from the start location to a pseudo-home cage with 0 or 1 error(s) on two consecutive trials. We classify this as a low-stress behavior test because it does not rely on aversive stimuli to encourage exploration of the maze and learning of the task. The apparatus consists of a modular start box, a 4-arm maze body, and a goal box. At the end of the goal box is a pseudo-home cage that contains bedding similar to that found in the animal’s home cage and is specific to each animal for the duration of maze testing. It has been demonstrated previously that this pseudo-home cage provides sufficient reward to motivate mice to learn to navigate the maze1
. Here, we present the visualization of the Lashley III maze procedure in the context of evaluating age-related differences in learning and memory in mice along with a comparison of learning behavior in two different background strains of mice. We hope that other investigators interested in evaluating the effects of aging or stress vulnerability in mice will consider this maze an attractive alternative to behavioral tests that involve more stressful learning tasks and/or visual cues.
Neuroscience, Issue 39, mouse, behavior testing, learning, memory, neuroscience, phenotyping, aging
Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach
Institutions: Freie Universität Berlin, Charité Berlin, Freie Universität Berlin, Psychiatric University Hospital Zurich.
The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.
Behavior, Issue 84, Neuropsychological Testing, cognitive decline, age, tablet-computer, memory, attention, executive functions
Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury
Institutions: Rhode Island College, Rhode Island College.
Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.
Behavior, Issue 82, working memory, reference memory, hypoxia-ischemia, radial arm maze, water maze
Appetitive Associative Olfactory Learning in Drosophila Larvae
Institutions: University of Konstanz, University of Fribourg.
In the following we describe the methodological details of appetitive associative olfactory learning in Drosophila
larvae. The setup, in combination with genetic interference, provides a handle to analyze the neuronal and molecular fundamentals of specifically associative
learning in a simple larval brain.
Organisms can use past experience to adjust present behavior. Such acquisition of behavioral potential can be defined as learning, and the physical bases of these potentials as memory traces1-4
. Neuroscientists try to understand how these processes are organized in terms of molecular and neuronal changes in the brain by using a variety of methods in model organisms ranging from insects to vertebrates5,6
. For such endeavors it is helpful to use model systems that are simple and experimentally accessible. The Drosophila
larva has turned out to satisfy these demands based on the availability of robust behavioral assays, the existence of a variety of transgenic techniques and the elementary organization of the nervous system comprising only about 10,000 neurons (albeit with some concessions: cognitive limitations, few behavioral options, and richness of experience questionable)7-10
larvae can form associations between odors and appetitive gustatory reinforcement like sugar11-14
. In a standard assay, established in the lab of B. Gerber, animals receive a two-odor reciprocal training: A first group of larvae is exposed to an odor A together with a gustatory reinforcer (sugar reward) and is subsequently exposed to an odor B without reinforcement 9
. Meanwhile a second group of larvae receives reciprocal training while experiencing odor A without reinforcement and subsequently being exposed to odor B with reinforcement (sugar reward). In the following both groups are tested for their preference between the two odors. Relatively higher preferences for the rewarded odor reflect associative learning - presented as a performance index (PI). The conclusion regarding the associative nature of the performance index is compelling, because apart from the contingency between odors and tastants, other parameters, such as odor and reward exposure, passage of time and handling do not differ between the two groups9
Neuroscience, Issue 72, Developmental Biology, Neurobiology, Biochemistry, Molecular Biology, Physiology, Behavior, Drosophila, fruit fly, larvae, instar, olfaction, olfactory system, odor, 1-octanol, OCT, learning, reward, sugar, feeding, animal model
Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice
Institutions: Fujita Health University, Core Research for Evolutionary Science and Technology (CREST), National Institutes of Natural Sciences.
The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this test, mice are placed into a conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same conditioning chamber and a differently shaped chamber with presentation of the auditory cue. Freezing behavior during the test is measured as an index of fear memory. To analyze the behavior automatically, we have developed a video analyzing system using the ImageFZ application software program, which is available as a free download at http://www.mouse-phenotype.org/. Here, to show the details of our protocol, we demonstrate our procedure for the contextual and cued fear conditioning test in C57BL/6J mice using the ImageFZ system. In addition, we validated our protocol and the video analyzing system performance by comparing freezing time measured by the ImageFZ system or a photobeam-based computer measurement system with that scored by a human observer. As shown in our representative results, the data obtained by ImageFZ were similar to those analyzed by a human observer, indicating that the behavioral analysis using the ImageFZ system is highly reliable. The present movie article provides detailed information regarding the test procedures and will promote understanding of the experimental situation.
Behavior, Issue 85, Fear, Learning, Memory, ImageFZ program, Mouse, contextual fear, cued fear
A Multi-Modal Approach to Assessing Recovery in Youth Athletes Following Concussion
Institutions: Holland Bloorview Kids Rehabilitation Hospital, University of Toronto, University of Toronto.
Concussion is one of the most commonly reported injuries amongst children and youth involved in sport participation. Following a concussion, youth can experience a range of short and long term neurobehavioral symptoms (somatic, cognitive and emotional/behavioral) that can have a significant impact on one’s participation in daily activities and pursuits of interest (e.g.,
school, sports, work, family/social life, etc.
). Despite this, there remains a paucity in clinically driven research aimed specifically at exploring concussion within the youth sport population, and more specifically, multi-modal approaches to measuring recovery. This article provides an overview of a novel and multi-modal approach to measuring recovery amongst youth athletes following concussion. The presented approach involves the use of both pre-injury/baseline testing and post-injury/follow-up testing to assess performance across a wide variety of domains (post-concussion symptoms, cognition, balance, strength, agility/motor skills and resting state heart rate variability). The goal of this research is to gain a more objective and accurate understanding of recovery following concussion in youth athletes (ages 10-18 years). Findings from this research can help to inform the development and use of improved approaches to concussion management and rehabilitation specific to the youth sport community.
Medicine, Issue 91, concussion, children, youth, athletes, assessment, management, rehabilitation
Simultaneous Quantification of T-Cell Receptor Excision Circles (TRECs) and K-Deleting Recombination Excision Circles (KRECs) by Real-time PCR
Institutions: Spedali Civili di Brescia.
T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) are circularized DNA elements formed during recombination process that creates T- and B-cell receptors. Because TRECs and KRECs are unable to replicate, they are diluted after each cell division, and therefore persist in the cell. Their quantity in peripheral blood can be considered as an estimation of thymic and bone marrow output. By combining well established and commonly used TREC assay with a modified version of KREC assay, we have developed a duplex quantitative real-time PCR that allows quantification of both newly-produced T and B lymphocytes in a single assay. The number of TRECs and KRECs are obtained using a standard curve prepared by serially diluting TREC and KREC signal joints cloned in a bacterial plasmid, together with a fragment of T-cell receptor alpha constant gene that serves as reference gene. Results are reported as number of TRECs and KRECs/106
cells or per ml of blood. The quantification of these DNA fragments have been proven useful for monitoring immune reconstitution following bone marrow transplantation in both children and adults, for improved characterization of immune deficiencies, or for better understanding of certain immunomodulating drug activity.
Immunology, Issue 94, B lymphocytes, primary immunodeficiency, real-time PCR, immune recovery, T-cell homeostasis, T lymphocytes, thymic output, bone marrow output
Cortical Source Analysis of High-Density EEG Recordings in Children
Institutions: UCL Institute of Child Health, University College London.
EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1
. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2
, because the composition and spatial configuration of head tissues changes dramatically over development3
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.
Behavior, Issue 88, EEG, electroencephalogram, development, source analysis, pediatric, minimum-norm estimation, cognitive neuroscience, event-related potentials
An Investigation of the Effects of Sports-related Concussion in Youth Using Functional Magnetic Resonance Imaging and the Head Impact Telemetry System
Institutions: University of Toronto, University of Toronto, University of Toronto, Bloorview Kids Rehab, Toronto Rehab, Sunnybrook Health Sciences Centre, University of Toronto.
One of the most commonly reported injuries in children who participate in sports is concussion or mild traumatic brain injury (mTBI)1
. Children and youth involved in organized sports such as competitive hockey are nearly six times more likely to suffer a severe concussion compared to children involved in other leisure physical activities2
. While the most common cognitive sequelae of mTBI appear similar for children and adults, the recovery profile and breadth of consequences in children remains largely unknown2
, as does the influence of pre-injury characteristics (e.g. gender) and injury details (e.g. magnitude and direction of impact) on long-term outcomes. Competitive sports, such as hockey, allow the rare opportunity to utilize a pre-post design to obtain pre-injury data before concussion occurs on youth characteristics and functioning and to relate this to outcome following injury. Our primary goals are to refine pediatric concussion diagnosis and management based on research evidence that is specific to children and youth. To do this we use new, multi-modal and integrative approaches that will:
1.Evaluate the immediate effects of head trauma in youth
2.Monitor the resolution of post-concussion symptoms (PCS) and cognitive performance during recovery
3.Utilize new methods to verify brain injury and recovery
To achieve our goals, we have implemented the Head Impact Telemetry (HIT) System. (Simbex; Lebanon, NH, USA). This system equips commercially available Easton S9 hockey helmets (Easton-Bell Sports; Van Nuys, CA, USA) with single-axis accelerometers designed to measure real-time head accelerations during contact sport participation 3 - 5
. By using telemetric technology, the magnitude of acceleration and location of all head impacts during sport participation can be objectively detected and recorded. We also use functional magnetic resonance imaging (fMRI) to localize and assess changes in neural activity specifically in the medial temporal and frontal lobes during the performance of cognitive tasks, since those are the cerebral regions most sensitive to concussive head injury 6
. Finally, we are acquiring structural imaging data sensitive to damage in brain white matter.
Medicine, Issue 47, Mild traumatic brain injury, concussion, fMRI, youth, Head Impact Telemetry System
Assaying Locomotor, Learning, and Memory Deficits in Drosophila Models of Neurodegeneration
Institutions: University of Miami, Miller School of Medicine.
Advances in genetic methods have enabled the study of genes involved in human neurodegenerative diseases using Drosophila
as a model system1
. Most of these diseases, including Alzheimer's, Parkinson's and Huntington's disease are characterized by age-dependent deterioration in learning and memory functions and movement coordination2
. Here we use behavioral assays, including the negative geotaxis assay3
and the aversive phototaxic suppression assay (APS assay)4,5
, to show that some of the behavior characteristics associated with human neurodegeneration can be recapitulated in flies. In the negative geotaxis assay, the natural tendency of flies to move against gravity when agitated is utilized to study genes or conditions that may hinder locomotor capacities. In the APS assay, the learning and memory functions are tested in positively-phototactic flies trained to associate light with aversive bitter taste and hence avoid this otherwise natural tendency to move toward light. Testing these trained flies 6 hours post-training is used to assess memory functions. Using these assays, the contribution of any genetic or environmental factors toward developing neurodegeneration can be easily studied in flies.
Neuroscience, Issue 49, Geotaxis, phototaxis, behavior, Tau
Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice
Institutions: University of British Columbia.
The Morris Water Maze (MWM) was first established by neuroscientist Richard G. Morris in 1981 in order to test hippocampal-dependent learning, including acquisition of spatial memoryand long-term spatial memory 1
. The MWM is a relatively simple procedure typically consisting of six day trials, the main advantage being the differentiation between the spatial (hidden-platform) and non-spatial (visible platform) conditions 2-4
. In addition, the MWM testing environment reduces odor trail interference 5
. This has led the task to be used extensively in the study of the neurobiology and neuropharmacology of spatial learning and memory. The MWM plays an important role in the validation of rodent models for neurocognitive disorders such as Alzheimer’s Disease 6, 7
. In this protocol we discussed the typical procedure of MWM for testing learning and memory and data analysis commonly used in Alzheimer’s disease transgenic model mice.
Neuroscience, Issue 53, Morris Water Maze, spatial memory testing, hippocampal dependent learning, Alzheimer's Disease
Eye Tracking Young Children with Autism
Institutions: University of Texas at Dallas, University of North Carolina at Chapel Hill.
The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1
, promote early identification2
, and inform treatment3
. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7
. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8
and abnormal brain functioning9
, particularly during the processing of social information1,10-11
. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13
. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.
Medicine, Issue 61, eye tracking, autism, neurodevelopmental disorders, toddlers, perception, attention, social cognition
A Proboscis Extension Response Protocol for Investigating Behavioral Plasticity in Insects: Application to Basic, Biomedical, and Agricultural Research
Institutions: Arizona State University.
Insects modify their responses to stimuli through experience of associating those stimuli with events important for survival (e.g.
, food, mates, threats). There are several behavioral mechanisms through which an insect learns salient associations and relates them to these events. It is important to understand this behavioral plasticity for programs aimed toward assisting insects that are beneficial for agriculture. This understanding can also be used for discovering solutions to biomedical and agricultural problems created by insects that act as disease vectors and pests. The Proboscis Extension Response (PER) conditioning protocol was developed for honey bees (Apis mellifera
) over 50 years ago to study how they perceive and learn about floral odors, which signal the nectar and pollen resources a colony needs for survival. The PER procedure provides a robust and easy-to-employ framework for studying several different ecologically relevant mechanisms of behavioral plasticity. It is easily adaptable for use with several other insect species and other behavioral reflexes. These protocols can be readily employed in conjunction with various means for monitoring neural activity in the CNS via electrophysiology or bioimaging, or for manipulating targeted neuromodulatory pathways. It is a robust assay for rapidly detecting sub-lethal effects on behavior caused by environmental stressors, toxins or pesticides.
We show how the PER protocol is straightforward to implement using two procedures. One is suitable as a laboratory exercise for students or for quick assays of the effect of an experimental treatment. The other provides more thorough control of variables, which is important for studies of behavioral conditioning. We show how several measures for the behavioral response ranging from binary yes/no to more continuous variable like latency and duration of proboscis extension can be used to test hypotheses. And, we discuss some pitfalls that researchers commonly encounter when they use the procedure for the first time.
Neuroscience, Issue 91, PER, conditioning, honey bee, olfaction, olfactory processing, learning, memory, toxin assay
Training Synesthetic Letter-color Associations by Reading in Color
Institutions: University of Amsterdam.
Synesthesia is a rare condition in which a stimulus from one modality automatically and consistently triggers unusual sensations in the same and/or other modalities. A relatively common and well-studied type is grapheme-color synesthesia, defined as the consistent experience of color when viewing, hearing and thinking about letters, words and numbers. We describe our method for investigating to what extent synesthetic associations between letters and colors can be learned by reading in color in nonsynesthetes. Reading in color is a special method for training associations in the sense that the associations are learned implicitly while the reader reads text as he or she normally would and it does not require explicit computer-directed training methods. In this protocol, participants are given specially prepared books to read in which four high-frequency letters are paired with four high-frequency colors. Participants receive unique sets of letter-color pairs based on their pre-existing preferences for colored letters. A modified Stroop task is administered before and after reading in order to test for learned letter-color associations and changes in brain activation. In addition to objective testing, a reading experience questionnaire is administered that is designed to probe for differences in subjective experience. A subset of questions may predict how well an individual learned the associations from reading in color. Importantly, we are not claiming that this method will cause each individual to develop grapheme-color synesthesia, only that it is possible for certain individuals to form letter-color associations by reading in color and these associations are similar in some aspects to those seen in developmental grapheme-color synesthetes. The method is quite flexible and can be used to investigate different aspects and outcomes of training synesthetic associations, including learning-induced changes in brain function and structure.
Behavior, Issue 84, synesthesia, training, learning, reading, vision, memory, cognition
Community-based Adapted Tango Dancing for Individuals with Parkinson's Disease and Older Adults
Institutions: Emory University School of Medicine, Brigham and Woman‘s Hospital and Massachusetts General Hospital.
Adapted tango dancing improves mobility and balance in older adults and additional populations with balance impairments. It is composed of very simple step elements. Adapted tango involves movement initiation and cessation, multi-directional perturbations, varied speeds and rhythms. Focus on foot placement, whole body coordination, and attention to partner, path of movement, and aesthetics likely underlie adapted tango’s demonstrated efficacy for improving mobility and balance. In this paper, we describe the methodology to disseminate the adapted tango teaching methods to dance instructor trainees and to implement the adapted tango by the trainees in the community for older adults and individuals with Parkinson’s Disease (PD). Efficacy in improving mobility (measured with the Timed Up and Go, Tandem stance, Berg Balance Scale, Gait Speed and 30 sec chair stand), safety and fidelity of the program is maximized through targeted instructor and volunteer training and a structured detailed syllabus outlining class practices and progression.
Behavior, Issue 94, Dance, tango, balance, pedagogy, dissemination, exercise, older adults, Parkinson's Disease, mobility impairments, falls
Perceptual and Category Processing of the Uncanny Valley Hypothesis' Dimension of Human Likeness: Some Methodological Issues
Institutions: University of Zurich.
Mori's Uncanny Valley Hypothesis1,2
proposes that the perception of humanlike characters such as robots and, by extension, avatars (computer-generated characters) can evoke negative or positive affect (valence) depending on the object's degree of visual and behavioral realism along a dimension of human likeness
) (Figure 1
). But studies of affective valence of subjective responses to variously realistic non-human characters have produced inconsistent findings 3, 4, 5, 6
. One of a number of reasons for this is that human likeness is not perceived as the hypothesis assumes. While the DHL can be defined following Mori's description as a smooth linear change in the degree of physical humanlike similarity, subjective perception of objects along the DHL can be understood in terms of the psychological effects of categorical perception (CP) 7
. Further behavioral and neuroimaging investigations of category processing and CP along the DHL and of the potential influence of the dimension's underlying category structure on affective experience are needed. This protocol therefore focuses on the DHL and allows examination of CP. Based on the protocol presented in the video as an example, issues surrounding the methodology in the protocol and the use in "uncanny" research of stimuli drawn from morph continua to represent the DHL are discussed in the article that accompanies the video. The use of neuroimaging and morph stimuli to represent the DHL in order to disentangle brain regions neurally responsive to physical human-like similarity from those responsive to category change and category processing is briefly illustrated.
Behavior, Issue 76, Neuroscience, Neurobiology, Molecular Biology, Psychology, Neuropsychology, uncanny valley, functional magnetic resonance imaging, fMRI, categorical perception, virtual reality, avatar, human likeness, Mori, uncanny valley hypothesis, perception, magnetic resonance imaging, MRI, imaging, clinical techniques
Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction
Institutions: Rutgers University, Koç University, New York University, Fairfield University.
We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be controlled by one computer.
Behavior, Issue 84, genetics, cognitive mechanisms, behavioral screening, learning, memory, timing
Barnes Maze Testing Strategies with Small and Large Rodent Models
Institutions: University of Missouri, Food and Drug Administration.
Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land (Barnes) mazes. Improved performance over sessions or trials is thought to reflect learning and memory of the escape cage/platform location. Considered less stressful than water mazes, the Barnes maze is a relatively simple design of a circular platform top with several holes equally spaced around the perimeter edge. All but one of the holes are false-bottomed or blind-ending, while one leads to an escape cage. Mildly aversive stimuli (e.g.
bright overhead lights) provide motivation to locate the escape cage. Latency to locate the escape cage can be measured during the session; however, additional endpoints typically require video recording. From those video recordings, use of automated tracking software can generate a variety of endpoints that are similar to those produced in water mazes (e.g.
distance traveled, velocity/speed, time spent in the correct quadrant, time spent moving/resting, and confirmation of latency). Type of search strategy (i.e.
random, serial, or direct) can be categorized as well. Barnes maze construction and testing methodologies can differ for small rodents, such as mice, and large rodents, such as rats. For example, while extra-maze cues are effective for rats, smaller wild rodents may require intra-maze cues with a visual barrier around the maze. Appropriate stimuli must be identified which motivate the rodent to locate the escape cage. Both Barnes and water mazes can be time consuming as 4-7 test trials are typically required to detect improved learning and memory performance (e.g.
shorter latencies or path lengths to locate the escape platform or cage) and/or differences between experimental groups. Even so, the Barnes maze is a widely employed behavioral assessment measuring spatial navigational abilities and their potential disruption by genetic, neurobehavioral manipulations, or drug/ toxicant exposure.
Behavior, Issue 84, spatial navigation, rats, Peromyscus, mice, intra- and extra-maze cues, learning, memory, latency, search strategy, escape motivation
C. elegans Positive Butanone Learning, Short-term, and Long-term Associative Memory Assays
Institutions: Princeton University, Princeton University.
The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans
navigates its environment through neuron-specific detection of food and chemical odors1, 2
, and can associate nutritive states with chemical odors3
, and the pathogenicity of a food source5
Here, we describe assays of C. elegans
associative learning and short- and long-term associative memory. We modified an aversive olfactory learning paradigm6
to instead produce a positive response; the assay involves starving ~400 worms, then feeding the worms in the presence of the AWC neuron-sensed volatile chemoattractant butanone at a concentration that elicits a low chemotactic index (similar to Toroyama et al.7
). A standard population chemotaxis assay1 tests the worms' attraction to the odorant immediately or minutes to hours after conditioning.
After conditioning, wild-type animals' chemotaxis to butanone increases ~0.6 Chemotaxis Index units, its "Learning Index". Associative learning is dependent on the presence of both food and butanone during training. Pairing food and butanone for a single conditioning period ("massed training") produces short-term associative memory that lasts ~2 hours. Multiple conditioning periods with rest periods between ("spaced training") yields long-term associative memory (<40 hours), and is dependent on the cAMP Response Element Binding protein (CREB),6
a transcription factor required for long-term memory across species.8
Our protocol also includes image analysis methods for quick and accurate determination of chemotaxis indices. High-contrast images of animals on chemotaxis assay plates are captured and analyzed by worm counting software in MatLab. The software corrects for uneven background using a morphological tophat transformation.9
Otsu's method is then used to determine a threshold to separate worms from the background.10
Very small particles are removed automatically and larger non-worm regions (plate edges or agar punches) are removed by manual selection. The software then estimates the size of single worm by ignoring regions that are above a specified maximum size and taking the median size of the remaining regions. The number of worms is then estimated by dividing the total area identified as occupied by worms by the estimated size of a single worm.
We have found that learning and short- and long-term memory can be distinguished, and that these processes share similar key molecules with higher organisms.6,8
Our assays can quickly test novel candidate genes or molecules that affect learning and short- or long-term memory in C. elegans
that are relevant across species.
Neuroscience, Issue 49, memory, associative learning, C. elegans, chemotaxis, spaced training, behavior
A Neuroscientific Approach to the Examination of Concussions in Student-Athletes
Institutions: Elon University, Elon University, Duquesne University, Elon University.
Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually. Concussion as defined by the 2013 Concussion Consensus Statement “may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an ‘impulsive’ force transmitted to the head.” Concussions leave the individual with both short- and long-term effects. The short-term effects of sport related concussions may include changes in playing ability, confusion, memory disturbance, the loss of consciousness, slowing of reaction time, loss of coordination, headaches, dizziness, vomiting, changes in sleep patterns and mood changes. These symptoms typically resolve in a matter of days. However, while some individuals recover from a single concussion rather quickly, many experience lingering effects that can last for weeks or months. The factors related to concussion susceptibility and the subsequent recovery times are not well known or understood at this time. Several factors have been suggested and they include the individual’s concussion history, the severity of the initial injury, history of migraines, history of learning disabilities, history of psychiatric comorbidities, and possibly, genetic factors. Many studies have individually investigated certain factors both the short-term and long-term effects of concussions, recovery time course, susceptibility and recovery. What has not been clearly established is an effective multifaceted approach to concussion evaluation that would yield valuable information related to the etiology, functional changes, and recovery. The purpose of this manuscript is to show one such multifaceted approached which examines concussions using computerized neurocognitive testing, event related potentials, somatosensory perceptual responses, balance assessment, gait assessment and genetic testing.
Medicine, Issue 94, Concussions, Student-Athletes, Mild Traumatic Brain Injury, Genetics, Cognitive Function, Balance, Gait, Somatosensory
The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism
Institutions: University of Montréal, McGill University, University of Minnesota.
Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood 33
. To help improve this understanding, proton magnetic resonance spectroscopy (1
H-MRS) can be used as it allows the in vivo
quantification of brain metabolites such as γ-aminobutyric acid (GABA) and glutamate in a region-specific manner 41
. In fact, a recent study demonstrated that 1
H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration 34
. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with 1
H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices 27,30,31
. Methodological factors to consider and possible modifications to the protocol are also discussed.
Neuroscience, Issue 93, proton magnetic resonance spectroscopy, transcranial direct current stimulation, primary motor cortex, GABA, glutamate, stroke
Quantifying Cognitive Decrements Caused by Cranial Radiotherapy
Institutions: University of California Irvine .
With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For many patients afflicted with CNS and non-CNS malignancies, radiotherapy and chemotherapy offer the best options for disease control. These treatments however come at a cost, and nearly all cancer survivors (~11 million in the US alone as of 2006) incur some risk for developing cognitive dysfunction, with the most severe cases found in patients subjected to cranial radiotherapy (~200,000/yr) for the control of primary and metastatic brain tumors1
. Particularly problematic are pediatric cases, whose long-term survival plagued with marked cognitive decrements results in significant socioeconomic burdens2
. To date, there are still no satisfactory solutions to this significant clinical problem.
We have addressed this serious health concern using transplanted stem cells to combat radiation-induced cognitive decline in athymic rats subjected to cranial irradiation3
. Details of the stereotaxic irradiation and the in vitro culturing and transplantation of human neural stem cells (hNSCs) can be found in our companion paper (Acharya et al., JoVE reference). Following irradiation and transplantation surgery, rats are then assessed for changes in cognition, grafted cell survival and expression of differentiation-specific markers 1 and 4-months after irradiation. To critically evaluate the success or failure of any potential intervention designed to ameliorate radiation-induced cognitive sequelae, a rigorous series of quantitative cognitive tasks must be performed. To accomplish this, we subject our animals to a suite of cognitive testing paradigms including novel place recognition, water maze, elevated plus maze and fear conditioning, in order to quantify hippocampal and non-hippocampal learning and memory. We have demonstrated the utility of these tests for quantifying specific types of cognitive decrements in irradiated animals, and used them to show that animals engrafted with hNSCs exhibit significant improvements in cognitive function3
The cognitive benefits derived from engrafted human stem cells suggest that similar strategies may one day provide much needed clinical recourse to cancer survivors suffering from impaired cognition. Accordingly, we have provided written and visual documentation of the critical steps used in our cognitive testing paradigms to facilitate the translation of our promising results into the clinic.
Medicine, Issue 56, neuroscience, radiotherapy, cognitive dysfunction, hippocampus, novel place recognition, elevated plus maze, fear conditioning, water maze
Using Learning Outcome Measures to assess Doctoral Nursing Education
Institutions: Harris College of Nursing and Health Sciences, Texas Christian University.
Education programs at all levels must be able to demonstrate successful program outcomes. Grades alone do not represent a comprehensive measurement methodology for assessing student learning outcomes at either the course or program level. The development and application of assessment rubrics provides an unequivocal measurement methodology to ensure a quality learning experience by providing a foundation for improvement based on qualitative and quantitatively measurable, aggregate course and program outcomes. Learning outcomes are the embodiment of the total learning experience and should incorporate assessment of both qualitative and quantitative program outcomes. The assessment of qualitative measures represents a challenge for educators in any level of a learning program. Nursing provides a unique challenge and opportunity as it is the application of science through the art of caring. Quantification of desired student learning outcomes may be enhanced through the development of assessment rubrics designed to measure quantitative and qualitative aspects of the nursing education and learning process. They provide a mechanism for uniform assessment by nursing faculty of concepts and constructs that are otherwise difficult to describe and measure. A protocol is presented and applied to a doctoral nursing education program with recommendations for application and transformation of the assessment rubric to other education programs. Through application of these specially designed rubrics, all aspects of an education program can be adequately assessed to provide information for program assessment that facilitates the closure of the gap between desired and actual student learning outcomes for any desired educational competency.
Medicine, Issue 40, learning, outcomes, measurement, program, assessment, rubric
Morris Water Maze Experiment
Institutions: Michigan State University (MSU).
The Morris water maze is widely used to study spatial memory and learning. Animals are placed in a pool of water that is colored opaque with powdered non-fat milk or non-toxic tempera paint, where they must swim to a hidden escape platform. Because they are in opaque water, the animals cannot see the platform, and cannot rely on scent to find the escape route. Instead, they must rely on external/extra-maze cues. As the animals become more familiar with the task, they are able to find the platform more quickly. Developed by Richard G. Morris in 1984, this paradigm has become one of the "gold standards" of behavioral neuroscience.
Behavior, Issue 19, Declarative, Hippocampus, Memory, Procedural, Rodent, Spatial Learning
Brain Imaging Investigation of the Memory-Enhancing Effect of Emotion
Institutions: University of Alberta, University of Illinois, Urbana-Champaign, Duke University, University of Illinois, Urbana-Champaign.
Emotional events tend to be better remembered than non-emotional events1,2
. One goal of cognitive and affective neuroscientists is
to understand the neural mechanisms underlying this enhancing effect of emotion on memory. A method that has proven particularly influential in the
investigation of the memory-enhancing effect of emotion is the so-called subsequent memory paradigm (SMP). This method was originally used to investigate the
neural correlates of non-emotional memories3
, and more recently we and others also applied it successfully to studies of emotional memory (reviewed in4, 5-7
Here, we describe a protocol that allows investigation of the neural correlates of the memory-enhancing effect of emotion using the SMP in conjunction with
event-related functional magnetic resonance imaging (fMRI). An important feature of the SMP is that it allows separation of brain activity specifically
associated with memory from more general activity associated with perception. Moreover, in the context of investigating the impact of emotional stimuli,
SMP allows identification of brain regions whose activity is susceptible to emotional modulation of both general/perceptual and memory-specific processing.
This protocol can be used in healthy subjects8-15
, as well as in clinical patients where there are alterations in the neural correlates of emotion perception
and biases in remembering emotional events, such as those suffering from depression and post-traumatic stress disorder (PTSD)16, 17
Neuroscience, Issue 51, Affect, Recognition, Recollection, Dm Effect, Neuroimaging


MS FATIGUE – A TOUGH PROBLEM
Fatigue is the common symptom in multiple sclerosis, reported by over 80% of patients. Along with cognitive impairment, it is the most important reason that MS patients stop working. Why does it happen and how can it be treated?
There are three forms of fatigue;
- “Normal” fatigue affects all of us.
- “Secondary” fatigue is caused by, say, lack of sleep, depression, pain, fever, and dehydration. Some MS medications used to treat spasticity, pain, depression, urinary symptoms, sleep, and anxiety can cause fatigue.
- “Primary” fatigue may be unique to MS and other autoimmune disorders. It is described as overwhelming, is not sleepiness or deconditioning and does not improve with rest.
So, what causes primary fatigue? Importantly, new or worsening severe fatigue for which no cause be found is often a relapse and should not be ignored as it indicates inadequate control of the disease. In fact, patients prone to fatigue may have distinct structural and functional MRI abnormalities in certain areas of the brain. Be careful not to blame patients for being fatigued.
Treating fatigue in MS is a challenge. Look carefully at every medication. Focus on depression, stress, sleep, and pain. MS symptoms come in “clusters.” Be sure there is not ongoing “subclinical” disease activity that could be controlled with a different disease-modifying-therapy. Encourage exercising to tolerance. Anything is better than nothing. Walk to the mailbox. Use cooling vests. Try medications such as amantadine, modafinil, di-fampridine, or even amphetamines. But don’t give up!


Psychotherapy is a general term for treating mental health problems by talking with a psychologist or other mental health provider. During psychotherapy, you learn about your condition and your moods, feelings, thoughts and behaviors. Psychotherapy helps you learn how to take control of your life and respond to challenging situations with healthy coping skills.
There are many specific types of psychotherapy, each with its own approach. The type of psychotherapy that’s right for you depends on your individual situation. Psychotherapy is also known as talk therapy, counseling, psychosocial therapy or, simply, therapy.
Not everyone who benefits from psychotherapy is diagnosed with a mental illness. Psychotherapy can help with a number of life’s stresses and conflicts that can affect anyone. For example, it may help you:
In some cases, psychotherapy can be as effective as medications, such as antidepressants. However, depending on your specific situation, psychotherapy alone may not be enough to ease the symptoms of a mental health condition. You may also need medications or other treatments.
Don’t hesitate to schedule an appointment with one of our professionals today.Request an appointment


We may pay tribute to the Red, White, and Blue several times throughout the year—Memorial Day, Flag Day, Veteran’s Day—but the anniversary of our country’s founding is a prime opportunity to wax nostalgic about the things that made our country exceptional.
Indeed, Independence Day is the holiday we Americans associate most strongly with our heritage of liberty, and we like to celebrate with patriotic fervor. But when we say we’re proud to be Americans, what exactly are we proud of?
The political environment in which our country was forged had its share of polarization and conflict, but it saw principled leaders combining good policy (independence from a tyrannical regime) with solid actions (the subsequent Revolutionary War to defend that policy) and a passion for principles (dedication to a cause greater than one’s self).
Although my husband never saw combat—his enlistment didn’t coincide with any wars—his military training, as well as his own zest for history, strongly inform his grasp of our country’s heritage of freedom, liberty, and independence.
He will point out the anniversary of the Battle of Midway, D-Day, Pearl Harbor Day, and the anniversaries of most of the major battles in WWII, to say nothing of random facts relating to other lesser-known battles and events throughout the panoply of history.
Knowing the past can certainly give us a sense of appreciation for just how much has been done to secure our freedoms and what it took to bring us to where we are today.
Of course, we cover history as a part of our schoolwork. But we also strive to model reverence for our laws and traditions and honor for those who have served our country in the following ways:
- We seek out parades and try to attend local patriotic functions (sometimes ceremonies and speeches can get tedious for the younger ones, but we persevere).
- We tour historical monuments and visit battlefields and memorials.
- We memorize important texts. We recite the Pledge of Allegiance most school mornings, and I mean to get back on track with learning the Gettysburg Address, the Declaration of Independence, and the Preamble to the Constitution (ideally we’ll memorize the whole thing, but I think I may borrow a page from my dad’s book and offer my kids a nickel for every section they commit to memory).
- We learn the National Anthem (all four verses!) and study the history of other patriotic songs.
- We point out soldiers in uniform, police officers and other first responders, and others who serve our country and our community; and, when possible, we try to thank them for their service.
Beyond instilling in our children a respect for the heritage of our country, though, we want them to come to an understanding of why we’re proud to be Americans. Raising good citizens requires more than just instilling a generic love for country, however much we may be fond of our native country.
Don’t get me wrong—I love our National Anthem, I think our Flag is a grand icon, and I love patriotic parades and propaganda (“We Can Do It!”). But our patriotism has to be rooted in more than symbols, songs, and shared rituals.
We want our children to appreciate the values that undergird the ideas of American exceptionalism: the notion that all men are created equal, the idea that our rights come from God—not government—and the commitment to a common goal of freedom and liberty that involves mutual respect, responsibility, and self-sacrifice.
I try not be flippant when I tell my kids we should be proud to be Americans. After all, what did we do to qualify for this distinction, other than being born? For me, it’s shorthand for saying that I’m grateful to live in a country that values life and liberty. I’m thankful to all the people throughout history who have contributed to the realization of this vision of freedom. And I’m hopeful that we won’t be complacent in our present comforts but strive to better the state of those around the world still hungering for the kind of freedom we have experienced.
Photo Credit: All photos courtesy of Rose Focht


‘La Belgique docile’. Les autorités belges et la persécution des JuifsAt the request of the Belgian Senate, Cegesoma was entrusted with a study to look into the possible implication of the Belgian authorities in the identification, persecution and deportation of the Jewish population during the occupation period 1940-1944. The result is La Belgique docile, a reference work for everyone who wishes to have a better understanding of Belgium in the period 1930-1950.
Jules Coelst, the catholic mayor of Brussels (in this photograph in conversation with King Leopold III in 1939), symbol of the critical attitude of the Brussels authorities towards the so-called “Jewish question” in 1942.
La Belgique docile explains how the local and national authorities responded (or not) to the will of the occupier to find and deport the Jews. However, the study does not want to concentrate on the Jewish tragedy alone. The novelty of the study lies in the fact that an explanation is sought as to why these authorities reacted in a certain way. To this end, not only the war years were examined but also the 1930s. The mentality of the country's elites in those first years was particularly considered so as to reach a conclusion as to their behaviour during the war.
From the 1930s to the first post-war years, there was a very important change in the attitude and mentality of the Belgian authorities: from anti-Semitism to docile submissiveness and unease in recognising what was happening to the Jews. After 1918, Jews were a marked minority in Belgium and the economic crisis of the 1930s placed them in strong competition with certain Belgian social groups. The anti-Jewish sentiment grew especially among Belgian and Flemish nationalist groups and parties. As a result of the persecution in Germany, a lot of Jewish refugees arrived in Belgium from 1933 onward. At the German invasion in 1940 they were deported to France because they were considered German citizens. In 1942, about 1,500 of these Jews were transported via Drancy to Auschwitz. The Belgian authorities could not have foreseen this, but it was nevertheless the result of ill-considered security policies. The authorities cannot however hide behind their ignorance of the imminent tragedy. This was a policy supported by the majority of the Belgian governing circles. In these circles, in the second half of the 1930s, there was a very strong mixture of xenophobia and anti-Semitism. It is also important to realise that the focus was on “the German” as an enemy rather than on Nazism. This lack of insight in the ideological foundations of Nazi Germany explains among others the attitude towards the Jewish question, which seemed subordinate to the nationalist perception of the conflict.
Furthermore, liberal democracy suffered an enormous blow in the 1930s. As a result of the economic crisis, there was less faith in the traditional “laissez-faire” and quite a few people looked to Germany and Italy where authoritarian regimes had been installed. Moreover, several collaborationist parties had accomplished a disguised coup during the occupation by seizing high state functions, in particular that of Domestic Affairs. This seizure of power undermined even more the Belgian administration's capacity for democratic resistance.
A third and important factor were the unprepared circumstances in which the occupation took place. The experience of the First World War had shown the importance to keep as much power of governance as possible. The secretaries-general took over considerable powers from the absent ministers. But no clear legal instructions were available for the Belgian authorities as to the use of this power in the event of an occupation. That is why the occupier as well as the Belgian authorities and the economic and financial circles supported a rapid recovery of public life. Thus, after May 1940, the Belgian authorities were immediately immersed in an escalating dynamics of collaboration for which they were not prepared.
An open truck of an Antwerp moving company is loading Jewish (?) persons, men, women as well as children (Photo Auditorat general)
In the case of the persecution of the Jews, the Belgian authorities were not legally obliged to follow the orders of the occupier. The Hague Convention states (art. 46) that the occupier must respect “the honour and the rights of the family, the life of persons and private property, as well as religious convictions and worship”. Furthermore, the persecution of the Jews served only the politics of the enemy and not the public order of the occupied country. Why did the Belgian authorities comply with the occupier in the first place and why did they not make use of this article? Firstly, only 5 % of the Jews were Belgian citizens and therefore the issue concerned foreigners. Secondly, no one was willing to point at the moral and legal limitations of the collaboration policies which after all caused little friction. Finally, the latent xenophobic and anti-Semitic sentiment among the country's elite goes a long way to explain events.
In some cases, these opinions shifted somewhat in the course of the war. A good example is a comparison between the Brussels and Antwerp local administration from the spring of 1942 onward. The specific war context is crucial: it was no longer certain that Germany would win the war, the tide was turning. The Brussels catholic mayor Jules Coelst refused to distribute the Star of David among the Jewish population and he refused to assist in tracing the Jews in the context of the “employment in the East”. In Greater Antwerp however, the town administration and police did take part in the distribution of the Star of David and the collective round-ups of Jews. This difference can mostly be explained by a political-ideological factor. In 1940, the Antwerp town administration had, like the Brussels town administration, adjusted for pragmatic reasons to maximal politics of collaboration. The outcome was however different. For Antwerp, it was a proactive attempt to integrate itself in the German-Flemish New Order. Brussels remained patriotic-Belgian and decisively hostile to Germany. Except in Brussels and Liège, the Star of David was distributed in all of Belgium by the town administrations and when the massive deportation of the Jews started from the Dossin barracks in Mechelen, there was no official protest from the part of the Belgian authorities. They chose not to endanger the administrative collaboration because of the deportation of the Jewish foreigners. The occupier had (deceitfully) declared that Jews with Belgian nationality would not be deported.
It was not until October 1942 that there was a change in policy at the central administration, but this was irrespective of the deportation of the Jews. It was the result of the introduction of forced labour in Germany. The Allies' improved chances of victory also played a role here. It is no surprise that the “Jewish question” no longer played a role in this change in attitude. The Jews had as good as disappeared: they were either deported or in hiding. This did not lead to an official change in policy by the central authorities towards the Jews, but resulted in an official protest.
After the liberation, there was no acknowledgement of the importance of the Judeocide. The administrative authorities and the military justice decided that the Belgian authorities carried no responsibility in the deportation of the Jews in Belgium. There was enough knowledge on the issue and some authorities recognised the Judeocide in an informal way. The largest problem was the fact that no policy had been put in place, neither with regard to the persecution and punishment of the perpetrators, nor as far as the acknowledgement of the victims was concerned. There had been no proper legal preparations in London and no significant attempts to adjust this had been made after the liberation.
Why were there no adjustments and why was no policy developed with regard to the Jewish question? The priorities of the Belgian government lay elsewhere: political and socio-economical problems needed to be tackled. The Judeocide was not a political issue and there was no political resolve to deal with the moral, material and juridical problems of Jewish victims and their surviving relatives. In this matter, Belgium's attitude was not different from the other European countries. Furthermore, the Jews formed a small minority and most of them were still foreigners and therefore of no electoral consequence.
What is now the outcome of the persecution of the Jews in Belgium? It is generally assumed that some 28,900 Jews died while in detention, were murdered in Belgium or were deported from Mechelen and Drancy. This is 36.5% of the total death toll in Belgium during the Second World War.
We may conclude that the lack of administrative and juridical preparation for the occupation, but especially the xenophobic and anti-Semitic culture among leading circles as well as the decline of democracy in the 1930s and the war years, were probably decisive factors in the docile collaboration of the Belgian authorities on a national as well as a local level that eventually led to the disastrous results we know today. Had the authorities opposed the occupier's measures and refused to carry out their orders, a lot of Jews would probably have survived the war. Where the question of responsibility is concerned, there can be no misunderstanding: during the occupation the possibility remained to refuse to carry out certain tasks or to ignore certain demands.


A report recently released by the National Research Council called “Assessment of Intraseasonal to Interannual Climate Prediction and Predictability” examines the current state of medium-term climate forecasting–over time periods of a few weeks to a few years. It makes suggestions on how these forecasts might be improved.
The Earth Institute’s International Research Institute for Climate and Society is among a number of institutions that regularly produce climate predictions, such as seasonal or longer-term rainfall and temperature forecasts. These institutions, the report states, could increase the value of such products to decision makers by improving the procedures for archiving and disseminating the information. In addition, the report concludes that making advances in observational capabilities, statistical and dynamical models and data assimilation systems could improve our understanding of key climate processes, as well as improve the forecasts themselves.
IRI research scientist Lisa Goddard was on the committee that wrote the report. In a brief Q&A below, she discusses the publication and some of its key recommendations.
Q: First, why is such a report necessary?
LG: The report was primarily commissioned by the National Oceanic and Atmospheric Administration, which wanted an assessment of the current capabilities in seasonal prediction and what additional efforts might improve the quality of forecast information. We know we have some skill in predicting the climate on intraseasonal-to-interannual time scales. For the United States, much of this skill is realized during El Niño or La Niña events. In order to improve our skill, we would not only need better models, but more complete observing systems, as well as better techniques for inserting those observations into the models’ initial conditions for prediction. There are other aspects of the climate system that may influence the climate on these time scales, such as the stratosphere or land-atmosphere interactions. These will require much more research, observations, and modeling before the operational community can quantify their impact on intraseasonal-to-interannual predictions.
However, we wrote the report with a broader audience in mind. We included sections on the history of prediction, on how forecasts are made, plus the extensive observations, scientific research and operational efforts required to develop, improve and communicate these forecasts.
Q: The report recommends some “best practices” for improving the utility and accessibility of forecasts to researchers and decision makers. What are the major impediments that prevent the uptake of this information by these groups currently? Is there one best practice that stands out from the rest in your opinion?
LG: In my opinion, creating publicly-available archives of information associated with forecasts is paramount. IRI’s experience is that the needs of researchers, decision makers and others who would use climate forecasts, or the model predictions on which they are based, are too diverse and difficult for any operational center to address thoroughly. So making available the data from the models and the observations, as well as what considerations went into the issued forecasts is very important. It allows different communities to tailor or assess the information in ways that are more consistent with their decision processes or risk thresholds.
Q: The report also lays out some key research questions that need addressing if we are to improve our forecasts. Which of these intersect directly with your work and why are they important to answer?
LG: The focus of my research is on how to make the best use of available prediction information, especially to those who might be able to act on that information. This is related to the report’s recommendations on improving the development and understanding of multi-model ensemble prediction and merging statistical and dynamical techniques
I think this is an important issue because models are still deficient when it comes to representing some of the characteristics of the climate and its variability. These deficiencies aren’t necessarily the same from one model to the next. The better the models and their use of observations become, the more robust the data I have to plug into my own research. So the key research questions that others throughout the climate community are addressing to improve forecasts also intersect directly with my work.


Roller skating is a way of pleasure and amusement which have an enormous health benefits. There are many kinds of diseases can be prevented by having this exercise through Best Roller Skates. There have a significant amount of health benefits of roller skating that literally few people are knows. After a wide research and with the help of medical science & physicians we mention here top five health benefits of roller skating. This is given below with vital information and references
1. Roller Skating a way of burning calories and make fit
If you want to lose weight, there is no good option to do that without exercise. There are various types of exercises. Roller skating is one of those. It is a sport as well as an appropriate exercise in case of weight loss. The prerequisite of weight loss is to burn out more calories than that of consuming every day. Roller skating burns up to 600 calories within one hour. Roller skating can reduce stress and change mood. It is also a way of increasing concentration on important things.
Besides burning calories, roller skating can be a nice source of transportation too. You can go wherever you want to by using best roller skate. You can develop a community through roller skating.
2. Decrease diseases and improve health
Health is wealth. This proverb is undoubtedly true. To become healthy, you need to do physical exercise and should follow a nutritious diet chart. While roller skating, your brain also gets a work-out along with your body.
Currently, heart disease is an vital issue that is growing day by day. Factors that are directly or indirectly contributing to the increase of heart disease are age, high blood pressure, poor diet, smoking etc. A cool and amazing way to fighting this state is roller skating. Roller skating can develop a person’s heart, mental health as well as psychological health. It prevents cardiovascular diseases as it is such an exercise that needs the concentration of whole body.
A very common disease like heart disease is diabetes and at present, it is not such a disease that happens because of age. It can happen to anyone at any age. Unhealthy way of having food, inappropriate lifestyle, overweight, lack of aerobic exercise, etc. often generate type 2 diabetes. You can control your diabetes or possibilities of having diabetes by the effective use of roller skating. Roller skating can strengthen the bones and heart, reduce stress, lessen blood glucose levels, and develop cholesterol levels. These are also the factors that affect diabetes. So you can manage all of these factors as well as diabetes by the proper use of roller skating.
3. Providing a stress-free life
Stress is identical to our routine life. Very few person are free from stress about someone or something. Almost each person are somehow stressed about things like work, health, family, friends, personal relationships, money, etc. Stress can become precarious to a person if it doesn’t minimized or decreased. Even it can cause death too. Because of these, you definitely need to give enough effort to lessen the level of stress. Besides other sports or exercises, it is the best that can help you to reduce stress. There are lots of people who think that skating is a tiresome sport. But roller skating can be fun for you if you can use the best roller skates for skating. It is also a relaxing activity if you use skating as that way. You can enjoy the scenic beauty of nature get the fresh air by skating every morning. It will certainly minimize your stress level.
According to medical science skating is a very helpful task that control the stress level and provides freshness through passing hormone via bloods.Morever,living a healthy life is very necessary to extend life span of human beings , roller skating acts here indirectly like a beneficiary by providing different healthy life style.
4. Roller Skating is a way of keeping balance and reducing injuries
There are some people who can balance themselves naturally. But for a lot of people balance does not come in a natural way. You need proper balance in case of walking, sitting, or doing several sports, and different activities. In case of decreasing fatigue, you also need a good balance because good balance can lessen the amount of energy. Balance is a prerequisite of roller skating as you need to keep balance to do skating properly and to learn different techniques of skating. By using best roller skate, you can ensure your safety as well.
You can also shun different types of injuries by the proper use of roller skating. Because by skating with best roller skates your muscles , bones even in immune system get enough scope to develop. By this way your body parts get sufficient flexibility to move and grow. Injuries which is mainly formed from less flexibility, less movement and fewer exercise as well. So it’s a injuries remover too.
5. Roller Skating can make you cheerful and happy
Happiness is a relative thing that every person wants. But very few people get it. In addition to physical benefits, best roller skating can develop your psychological health. Roller skating is a way to fresh up your mind and make you free from depression. It can make you happy too. To minimize bad hormone and maximize good hormone, best roller skate can be very helpful. By skating regularly, you will feel good naturally. Roller skating can develop your skating skill and techniques. You can combine your mood with roller skating. You can also join in a group of people who like to roller skate. It can be a fun and a way of communication with others. So it is obvious that roller skating can make you happy buy rolling around the nature.
Anxiety is nowadays a common thing that has from young to old age people. According to physician for removing anxiety need healthy lifestyle, traveling with amusement , involving in sports etc. And fortunately, in roller skating have these all so it’s a anxious remover literally.
Health is an essential factor of our living being. Though there have various exercise, tasks, and ways which are beneficial to our health, limited options have fun with thse ways. Among this limited options roller skating is one the best way of having fun and enjoyment with health benefits. It is not too luxurious to pay for. Moreover, persons who don’t like to go to the gym or have aerobic exercises can simply use roller skate and get the body work out perfeclty with joy. So this is like a pro with dual advantage. Be a skater.


High schools provide many activities for students, which they can use to fill out their life experiences. In all activities, students work with peers, take constructive criticism and follow a leader. Other students will practice leadership and management skills. Teens also will learn skills specific to the activities, and the essence of these lessons will increase a student's chance of success later in life.
Students can run for student council or other student governments. These activities often have constitutions that students must follow, and strict meeting procedures. Structured activity programs create peer groups with higher aspirations and more commitment to academic success, according to Extracurricular Activities and Student Achievement: Everyone Gains. Students will lead how meetings are run and how to organize their peers. These practices will contribute to successful relationships in college and later at work.
Volunteer work can show students how others live, especially in the instance of soup kitchens or special care homes. Students gain perspective about their current and future lives while caring for others in difficult circumstances. Practicing compassion and dealing with different populations also forces students to strengthen their communication skills, another bonus for later life success.
Clubs are typically smaller than other extracurricular activities. This allows students who dislike large groups to build confidence and character while exploring specific topics such as gaming or bead work with a close-knit group. Involvement can expand their interests and develop hobbies, which can lead to future careers.
Extracurricular activities might have a direct connection to classes, such as math and science groups, or the speech team. Teachers often know more about what they teach than needed to teach high school students, but most teachers are willing to share their knowledge with an interested group of students. Students can see a future that relates to a specific field and their interests can lead the exploration. Furthermore, students can relate to peers with similar interests, making them excited about their future successes.
Students involved in sports get the benefits similar to other activities, with the added benefit of health. Students who are physically active might perform better in class and increase concentration and attentiveness in the classroom, according to Let's Move. Additionally, students can form life-long health habits that will contribute to future successes.


Spring has sprung early in Michigan, which means more people are experiencing allergy symptoms sooner than in years past.
According to the Centers for Disease Control and Prevention, allergies are the sixth leading cause of chronic illness in the United States with an annual cost in excess of $18 billion. More than 50 million Americans suffer from allergies each year.
Allergies are defined as an overreaction of the immune system to substances that generally do not affect other individuals.
These allergens can cause a runny nose, stuffy nose (congestion), sneezing, coughing and itchy and watery eyes, just to name a few.
Some allergies are seasonal, such as what many people currently are experiencing since many trees and plants are beginning to bloom.
A number of different allergens are responsible for allergic reactions. The most common include pollen, dust, food, insect stings, animal dander, mold, medications and latex.
Anyone may have or develop an allergy — in fact, adults who have never experienced allergy symptoms can be affected suddenly.
Allergies generally cannot be prevented. Avoiding triggers once a person knows what affects them often can help. A person with indoor allergies to dust, dust mites and animal dander can avoid these triggers, just as a person with outdoor allergies to trees, grass and pollen can avoid those.
Those experiencing allergy symptoms should try these techniques to minimize contacts with triggers:
• Limit outdoor activities on days with high pollen counts.
• Keep windows closed (at home or in the car) to keep pollens out.
• Take a shower after coming indoors. Otherwise, pollen in your hair or on your skin may bother you all night and transfer to your bed linens as well.
When avoidance doesn't work, recommended treatments are over-the-counter medications such as a saline nasal spray, antihistamines, steroid nasal sprays and others up to or including a referral to a specialist for allergy testing.
Laura Grima, M.D., is a family medicine physician who practices at Mercy Memorial Family Medicine-Dundee. Her office is located at 100 Main St., Dundee, and she can be reached by calling 823-5906.


Trade and Allowances
CARBON MARKETS are a false solution to the climate crisis. They are a market based approach to reducing CO2 emissions. Carbon Markets allow countries or polluters to buy offsets or carbon credits, allowing them to purchase the right to emit more. They are a dangerous distraction to climate action, as they have not only failed to reduce carbon emissions in the past (see the UN’s Clean Development Mechanism (CDM) or the EU’s Emission Trading System (ETS)), but they have also detrimentally impacted human rights while simultaneously commodifying nature and allowing for “business as usual.” In this section, you will learn about the dangers of carbon markets and why they are not a real solution to the climate crisis.
Climate Justice Brief #8
The Dangers of Carbon Markets
Multiple civil society organizations, nov 2010
This policy brief explains the history of carbon markets, and why they will increase pollution, serve large corporations, and capture the remainder of the carbon budget for developed countries. Though this brief is from 2010 and in reference to the Koyoto Protocol, it still provides a good overview of the main issues surrounding carbon markets.
Tags: carbon markets, clean development mechanism, clean technologies
Carbon Markets Are Not a Climate Solution
By: ActionAid, IPS, Friends of the earth EWNI, LDC-Watch, Jubliee South APMDD, PACJA, Plataforma Boliviana, Third World Network, feb 2015
This brief urges international negotiators to realize that “a ‘price on carbon’ should not mean a global carbon-market. Instead, it must mean that polluters pay a real cost for the damage from their greenhouse gas emissions.” The authors describe the risks of a global carbon market, and the relation carbon markets have to the Paris Agreement.
Tags: carbon offset markets, risks of a global carbon market, key numbers, paris agreement
In Your Wildest Schemes: The Market vs. the Climate
By: Sam Wallman, 2013
With incredible imagery and quotations, Wallman provides an overview on how the free market has caused climate change and is failing to solve it. This failure is inspiring climate justice.
Tags: free market, climate change, climate justice
Carbon markets 101: The Ultimate Guide to Global Offsetting Mechanisms
By Carbon Market Watch
This guide outlines the basics of carbon markets, the difference between carbon offsets and cap and trade, and outlines some examples of different carbon markets.
Tags: carbon markets, CORSIA, REDD+, Article 6, carbon offsets
CORSIA: A False Solution to the Very Real Threat of Emmissions from Aviation.
By: BioFuel Watch
An Example of a failed carbon market and why carbon markets are dangerous distractions. "The UN’s International Civil Aviation Organization (ICAO) proposes to achieve “carbon neutral emissions growth” for the aviation industry using “alternative” fuels and forest offsets, under a scheme called CORSIA (Carbon Offsetting and Reduction Scheme for International Aviation). But CORSIA is a dangerous, deeply flawed distraction that will result in more, not less emissions. A 2018 open letter from 96 civil society organizations around the globe called for CORSIA to be rejected, calling it “a boon to airlines, a disaster for the climate and a threat to forests and communities.”
Tags: CORSIA, carbon markets, dangerous distractions, corporations, capitalism


Thousands of routers, modems, IP cameras, VoIP phones and other embedded devices share the same hard-coded SSH (Secure Shell) host keys or HTTPS (HTTP Secure) server certificates, a study found.
By extracting those keys, hackers can potentially launch man-in-the-middle attacks to intercept and decrypt traffic between users and millions of devices.
Researchers from security firm SEC Consult analyzed firmware images for over 4,000 models of embedded devices from more than 70 manufacturers. In them they found over 580 unique private keys for SSH and HTTPS, many of them shared between multiple devices from the same vendor or even from different ones.
When correlating those 580 keys with data from public Internet scans, they found that at least 230 keys are actively used by over 4 million Internet-connected devices. Around 150 of the HTTPS server certificates they recovered are used by 3.2 million devices and 80 of the SSH host keys are used by 900,000 devices.
The remaining keys might be used by many other devices that cannot be accessed from the Internet, but are still vulnerable to man-in-the-middle attacks inside their respective local area networks.
SSH host keys are used to verify the identity of a device that runs an SSH server. When users connect to such a device for the first time over the encrypted SSH protocol, they get prompted to save the device's public key, which is part of a public-private key pair.
On subsequent connections, the server's identity will be verified automatically based on the public key stored on the user's SSH client and the private key stored on the device.
If an attacker steals the device's SSH host private key and is in a position to intercept the user's connection attempts, he can impersonate the device and trick the user's computer to talk to his machine instead.
A similar attack is possible if attackers gain access to a device's HTTPS private certificate, which is used to encrypt communications between users and its Web-based management interface.
Furthermore, if attackers can capture encrypted HTTPS traffic between users and a legitimate device and know that device's HTTPS private key, they can decrypt the traffic at a later time to extract usernames, passwords and other authentication tokens.
SEC Consult's analysis revealed that many embedded device manufacturers hard-code the same private keys across their own products. However, there were also cases where the same keys were found in products from different manufacturers.
Those situations are typically the result of vendors building their firmware based on software development kits (SDKs) received from chipset makers, without bothering to change the keys that are already present in those SDKs.
For example, a certificate issued to a person named "Daniel" with the email address firstname.lastname@example.org was found in firmware from Actiontec, Aztech, Comtrend, Innatech, Linksys, Smart RG, Zhone and ZyXEL, the SEC Consult researchers said. The certificate comes from a Broadcom SDK and is used by over 480,000 devices on the Internet, they said.
In another case, a certificate issued to a company called Multitech from Bangalore, India, was found in firmware from Aztech, Bewan, Observa Telecom, NetComm Wireless, Zhone, ZTE and ZyXEL. That certificate was tracked to an SDK for ADSL2+ routers from Texas Instruments and is used by over 300,000 devices on the Web.
Another 80,000 devices, mostly WiMAX gateways from Green Packet, Huawei Technologies, Seowon Intech, ZTE and ZyXEL, use a "MatrixSSL Sample Server Cert" certificate.
There are several reasons why so many devices are accessible from the Internet via HTTPS and SSH. These include insecure default configurations by manufacturers, automatic port forwarding via UPnP, and provisioning by ISPs, which configure their subscribers' devices for remote access and management, the researchers said in their report.
"Vendors should make sure that each device uses random, unique cryptographic keys," the researchers said. "These can be computed in the factory or on first boot. In the case of CPE [customer premises equipment] devices, both the ISP and the vendor have to work together to provide fixed firmware for affected devices."
Where possible, users should change the SSH host keys and HTTPS certificates on their devices. Unfortunately, this requires technical knowledge beyond that of an average home user and is, in many cases, impossible, especially on devices that have been locked down by ISPs.


In-depth knowledge for the future
Within our research papers, we develop scientific and methodological principles for improving environmental performance at all three levels of the state (the federal governments, the cantons, the municipalities) or undertake systematic evaluations of the environmental impact of technologies and processes that have not
The Federal Offices for the Environment (FOEN) and of Energy (SFOE) regularly announce applied research studies relating to the environment. The importance of research into the generation and transportation of energy has significantly increased as a result of the 2050 Energy Strategy. In addition, the commitment to the permanent domestic disposal of radioactive waste produced in Switzerland necessitates extensive research into sites for deep geological repositories.
- Evaluating the impact of power plants on all areas of the environment and on sustainable development
- Evaluating the ecological aspects of hydroelectric plants and other power generating plants
- Examining and assessing the environmental impact of the surface level and underground elements of any potential deep geological repository sites
- Expertise to support practical implementation across all environmental sectors
- Writing readily understandable versions of technically demanding papers for public release


What is Continuous Delivery?
By: Sam Guckenheimer
Continuous Delivery (CD) is the process to build, test, configure and deploy from a build to a production environment. Multiple testing or staging environments create a Release Pipeline to automate the creation of infrastructure and deployment of a new. Successive environments support progressively longer-running activities of integration, load, and user acceptance testing. Continuous Integration starts the CD process and the pipeline stages each successive environment the next upon successful completion of tests.
Continuous Delivery may sequence multiple deployment “rings” for progressive exposure (also known as “controlling the blast radius”). Progressive exposure groups users who get to try new releases to monitor their experience in “rings.” The first deployment ring is often a “canary” used to test new versions in production before a broader rollout. CD automates deployment from one ring to the next and may optionally depend on an approval step, in which a decision maker signs off on the changes electronically. CD may create an auditable record of the approval in order to satisfy regulatory procedures or other control objectives.
Without Continuous Delivery, software release cycles were previously a bottleneck for application and operation teams. Manual processes led to unreliable releases that produced delays and errors. These teams often relied on handoffs that resulted in issues during release cycles. The automated release pipeline allows a “fail fast” approach to validation, where the tests most likely to fail quickly are run first and longer-running tests happen after the faster ones complete successfully.
Continuous Delivery is a lean practice. The goal of CD is to keep production fresh by achieving the shortest path from the availability of new code in version control or new components in package management to deployment. By automation, CD minimizes the time to deploy and time to mitigate or time to remediate production incidents (TTM and TTR). In lean terms, this optimizes process time and eliminates idle time. Continuous Delivery is helped considerably by the complementary practices of Infrastructure as Code and Monitoring.
Continuously delivering value has become a mandatory requirement for organizations. To deliver value to your end users, you must release continually and without errors.
Continuous Delivery also supports two other patterns for progressive exposure beside sequential rings. “Blue/Green deployment” relies on keeping an existing (blue) version live while a new (green) one is deployed. Typically, this uses load balancing to direct increasing amounts of traffic to the green deployment. If monitoring discovers an incident, traffic can be rerouted to the blue deployment still running. “Feature flags” (or “feature toggles”) comprise another technique used for experimentation and “dark launches.” Feature flags turn on features on or off for different end users based on their identity and group membership.
Modern release pipelines allow development teams to deploy new features fast and safely. Issues found in production can be remediated quickly by rolling forward with a new deployment. In this way, CD creates a continuous stream of customer value.
Read more about the Continuous Delivery capabilities of Azure Pipelines.
Learn how to set up Continuous Deployment to Azure.
See how Bing is using Continuous Delivery with Azure DevOps.
|Sam Guckenheimer works on Microsoft Azure DevOps team. He acts as the chief customer advocate, responsible for strategy of the next releases of these products, focusing on DevOps. He has written four books on DevOps and Agile Software practices.|
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