Archived | Autism Speaks: Summaries of Funded Studies (Mentor Based Fellowships) | Circa 2007 #NotAnAutisticAlly #AutisticHistory

Summaries of Funded Studies (Mentor Based Fellowships) 

Summaries of Funded Studies (Mentor Based Fellowships) 
$3 Million for 43 fellowships 

In order to assure that autism research continues to expand and grow in the future, the training of the “next generation” of autism researchers is essential. These researchers need access to current knowledge and the most advanced techniques. 

The generosity of Autism Speaks supporters over the past year has allowed 43 mentor-based fellowships to be awarded, totaling approximately $3 million in new funding commitment this year, more than double the number of awards made in 2005.

This program provides the necessary financial support and professional guidance for young investigators interested in focusing on autism as a career. Fellowships typically provide a stipend and professional support for two years.

In the past, over 80 percent of fellows funded by Autism Speaks continued in the field of autism research, making important contributions in a wide range of fields of autism. This includes, but is not limited to: cognitive and behavioral development, early diagnosis and intervention, language acquisition, neurobiology, neuropathology, neurotoxicology, epidemiology, and treatment. 

The following research proposals were evaluated based on the quality of the research plan as well as the training environment provided to the candidate fellow. In addition to making important contributions to the field and increasing our understanding of autism, the fellowships have the added benefit of allowing young researchers to pursue a research career in the field. 

All grant applications were reviewed and approved by the Autism Speaks Scientific Advisory Board together with a group of panel reviewers. Final recommendations were presented to and approved by the Autism Speaks Board of Directors on Dec. 7, 2006.

Animal Models: 13 Fellowships

Brain Structure and Function: 9 Fellowships

Immune System Function: 3 Fellowships

Intervention and Treatment: 3 Fellowships

Screening and Diagnosis in High Risk Populations: 2 Fellowships

Role of Genes and Environment: 9 Fellowships

Language, Cognition and Repetitive Behaviors: 4 Fellowships

How can animal models teach scientists about autism?

Mentor: Jocelyne Bachevalier, Ph.D.
Yerkes National Primate Research Center, Emory University
Pre-doctoral Fellow: Christa Payne

The Integration of Multisensory Social Cues and its Neural Basis in Monkeys

People with autism are characterized by problems with social cognition. However, the cause of these problems is still unclear.

Dr. Bachevalier has developed a program of research to study the neural basis of social cognition impairments in autism. Her team works with a model of autism based in a group of rhesus monkeys with specific brain lesions in either the orbital frontal cortex or the amygdala. She and her colleagues have found that early dysfunction in the orbital frontal cortex and amygdala regions of the monkey brain results in social deficits similar to those seen in people with autism.

This study will use the same monkey model to investigate the theory that people with autism have difficulty integrating auditory and visual information and that this deficit is linked to their ability to interpret complex social signals. The researchers will also use positron emission tomography (PET) to examine which parts of the brain are active during a facial processing task. They will then compare their results to findings using a similar task in children with autism. These comparisons help researchers identify with greater precision the role of particular brain regions and circuits in basic social difficulties seen in people with autism.

What this means for people with autism: This study will use a powerful primate model of autism to test the idea that the difficulties people with autism have interpreting social signals may stem from an inability to integrate auditory and visual information. Data from this work will help pinpoint the neural structures involved in this kind of social cognition. And results from this work could be used to explore behavioral interventions aimed at helping people better interpret social signals.

Mentor: Aysenil Belger, Ph.D. 
University of North Carolina – Chapel Hill
Pre-doctoral Fellow: Kimberly Hills-Carpenter

The role of GABRA4 in the pathophysiology of autism 

Using a multidisciplinary approach, Dr. Belger will examine the role of the GABA receptor type A4 in autism – specific behaviors such as social interaction and social cognition.

First, an animal model will be utilized to determine the role of the GABA A4 receptor expression on amygdala development and social behaviors. In a parallel set of experiments, functional MRI will be utilized to observe the activity of the amygdale and hippocampus during visual stimuli which includes facial recognition and processing.

The overall goal is to determine the effect of altered GABRA4 function on limbic system functioning during social/affective processing and whether this mimics deficits observed in autism. It is hypothesized that lack of GABRA4 receptor expression will result in changes in amygdala volume and social processing deficits, similar to autism. 

What this means for people with autism: The primary aim of this proposal is to train the fellow as a translational neuroscientist who can integrate human cognitive neuroscience methodology with animal research to investigate the complex neurobiological underpinnings of autism. If it is found that the GABRA4 knockout mouse is a good animal model for autism, the effectiveness of benzodiazepine therapy in alleviating social deficits can be studied.

Mentor: Alexandra Joyner, Ph.D.
New York University, New York
Post-doctoral Fellow: Roy Sillitoe, Ph.D.

Cerebellum Circuit Formation in Engrailed Mutant Mice

It has long been known that people with autism have abnormalities in the cerebellum, a brain structure that controls movements and processes sensory information.

Neuropathological studies have reported a loss of cells in the cerebellum, called “hypoplasia”; however, it is unknown what causes this cellular defect. Dr. Joyner and her team have focused in part on a gene called ENGRAILED2 (En2), which other studies have linked to autism, hypothesizing that mutations of this gene lead to a loss of cells in specific areas of the cerebellum.

This hypoplasia may produce failure to execute particular motor and sensory brain operations that would normally emerge during early development and are typical of autism spectrum disorders.Using state-of-the-art molecular biology techniques, Drs. Joyner and Sillitoe will examine how neuronal circuits in the cerebellum are affected by loss of the En2 gene.

They will focus on one particular cell type, the Purkinje cells, which form the primary pathway in which the cerebellum connects with other parts of the brain.What this means for people with autism: This research will advance a promising line of research into abnormalities in the cerebellum and their role in autism. In particular, it will investigate how the En2 and En1 genes affect cell growth and neural circuitry in the cerebellum. This work will provide insight into specific cerebellum-associated deficits in autistic children and thus could lead to behavior modification protocols aimed at improving their prognosis. 

Mentor: James Millonig, Ph.D.
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School
Pre-doctoral Fellow: Silky Kamdar

Functional Examination of Candidate ENGRAILED 2 Disease Alleles by Mouse Transgenesis

Over the past several years Dr. Millonig and his colleagues at UM.D.NJ have narrowed in on the ENGRAILED 2 (EN2) gene in humans as a strong candidate gene for an autism spectrum disorder (ASD). They have found two DNA variants which are inherited more frequently in individuals with ASD as compared to their non-affected siblings. The next phase of Dr. Millonig’s research will focus on whether or not these specific genetic mutations lead to functional changes in the EN2 protein, and how this protein is expressed in the brain. 

Pre-doctoral fellow Silky Kamdar will work with Dr. Millonig to create two lines of mutant mice: one that expresses the suspected disease form of En2 and one that expresses the form of En2 not associated with ASD. Ms. Kamdar will examine these mice throughout development to determine if there is a difference in En2 protein between these mouse strains and when and where during development these differences can be detected. 

What this means for people with autism: This study will provide critical details about the role of the En2 gene in ASD – such as brain regions and cell types which are particularly susceptible to this genetic mutation. Findings from this research may lead to more targeted behavioral and pharmaceutical therapies.

Mentor: Michael Platt, Ph.D.
Duke University Medical Center, North Carolina
Pre-doctoral Fellow: Michael Simpson Bendiksby, Ph.D.

Neural Basis of Social Gaze-following Deficits Explored in an Animal Model

One of the most striking diagnostic features of autism is the failure use social cues to guide attention. The primate is a unique animal model of use to autism researchers since this animal will shift its attention to others based on gaze cues. This model of joint attention allows researchers a unique opportunity to investigate the neurobiological substrate of this behavior. The Platt lab has shown that the gaze-following behavior includes both reflex as well as cognitive processing. In this project, Dr. Platt and Steven Shepherd, a pre-doctoral fellow who bring expertise in electrophysiology, will study the impact of different stimuli on the social gaze. In addition, they will attempt to determine whether social gaze is influenced more by reflex or voluntary mechanisms. The activity of a particular group of neurons in a brain region called the lateral intraparietal area will be measured to examine their role in social gaze and attention to social cues.

Mentor: Michael Platt
Post-doctoral Fellow: Karli Watson, Ph.D.

The Neural Basis of Social Decision Making

Dr. Watson will work with Dr. Platt and Mr. Shepherd at Duke University Medical Center studying a primate model of social deficits. In this project, this research group will investigate the role of the orbito-frontal cortex (OFC) on a task which measures the motivational to see various images, including those of other monkeys.

A comprehensive study of the OFC neurons will determine whether there are neurons in the OFC that respond to social stimuli, those that do not, whether different OFC neurons respond differently to the various classes of social stimuli, and whether OFC functioning is critical to normal responses to social stimuli. To take this study a step further, they will also determine how the manipulation of neurochemical systems, particularly those involving oxytocin and serotonin, affects social motivation and OFC function in monkeys.

As dysregulation of the oxytocin and serotonin systems have been linked to deficits in social bonding and social recognition, this investigation will provide information to researchers interested in developing pharmacotherapies which target this behavior.

What this means for people with autism: These two fellowships will work under Dr. Michael Platt to utilize an animal model to better characterize and identify the neurobiological basis of social gaze, social attention and joint attention.

The molecular and biochemical systems responsible for social functioning also studied in the Platt laboratory could lead to the development of drugs designed to alleviate social pathologies found in autism, and the specific targets of such drugs on activity of brain regions which underlie social behavior.

Mentor: Samuel Pleasure M.D., Ph.D.
University of California San Francisco 
Fellow: Julie Siegenthaler, Ph.D.

The Meninges as a Signaling Center in Corticogenesis

The meninges (the area that immediately surrounds the brain) is now viewed as important in the development of the cerebral cortex, both as a physical barrier to migrating neuronal populations and as a source of developmental chemical signals.

Recent evidence has suggested a role the meninges in the development of the cerebral cortex, and specifically, the involvement of the Foxc1 gene (a transcription factor found exclusively in the meninges) and TGF? (a growth factor).

This study will use rodents as a model system to investigate the significance of meningeal Foxc1 and TGF? signaling in corticogenesis, and is designed to address three specific questions:

(1) Why do mutations in Foxc1 lead to cortical dysgenesis?

(2) Is there a relationship between Foxc1 and TGF? signaling in the meninges?

(3) What is the importance of TGF? signaling in the meninges and in the developing cortex and in the adult cortex?

A variety of histological and biochemical techniques will be used.

What this means for people with autism: This proposal will point out important new mechanisms controlling prenatal and postnatal cortical development. In addition, it will help researchers better understand the types of cortical defects seen in a variety of neurodevelopmental disorders, including autism-spectrum disorders.

Mentor: Elizabeth Powell, Ph.D.
University of Maryland, Baltimore 
Pre-doctoral Fellow: Gabriela Martins

Importance of MET function on interneuron development

Newly published research has found that variations in the MET tyrosine kinase receptor are significantly associated with autism. It is estimated that presence of a specific allele may almost double the risk of developing the disorder.

Parallel to human genetic studies, MET signaling has been studied in animal models to determine the role of MET on brain development. MET has been shown to be responsible for normal migration of neurons by interacting with a molecule called hepatocyte growth factor/scatter factor (HGF/SF). Loss of this molecule (HGF/SF) leads to a reduction in the number of neurons which release GABA as a neurotransmitter, specifically a class of neurons called “interneurons”.

These interneurons connect with cells both within and outside specific brain regions to monitor and modulate normal activity levels. In this way, brain cells can integrate information from several different sources.

The current research program proposes to examine the role of HGF/SF and MET on the development of GABAergic inhibitory interneurons in the developing mouse embryo. The experiments will artificially eliminate HCF/SF-MET function where these interneurons are generated and link this back to impairments in proper migration of GABAergic interneurons.

The fellow on this project has a background in psychology and cognition, and will be trained on advanced molecular biology techniques to further examine if rescue of MET function can reverse these deficits.What this means for people with autism: This work is relevant to the growing body of evidence suggesting altered GABAergic signaling in the brains of individuals with autism and will specifically advance the understanding about embryonic perturbations in the development of GABAergic interneurons in the brain.

Mentor: Peter Scheiffele, Ph.D.
Columbia University
Post-doctoral Fellow: Fatiha Boukhtouche, Ph.D.

Molecular Mechanisms of Synapse Elimination in the Mouse Cerebellum

During early brain development, the cells in the brain go through a dynamic process of growth and building connections between some cells, termed “synaptogenesis”.

At the same, time, other neuronal connections are eliminated, or pruned back. Recent research has determined that the latter process is impaired in people with autism spectrum disorders (ASDs).

Dr. Scheiffele and his team have found that the gene alpha-chimaerin, which has been linked to autism in gene-linkage studies, may play a role in synapse elimination. Postdoctoral fellow Fatiha Boukhtouche will use an animal modify the levels of alpha chamaerin in Purkinje cells in the cerebellum. She will focus on this region since defects in this brain area have been most consistently linked to autism and this system undergoes extensive synapse elimination that can be easily studied using well-tested methods.

What this means for people with autism: Insights into the function of alpha-chimaerins in synapse elimination should be valuable not only for advancing the general knowledge of synapse elimination during neuronal development but should be instrumental for defining the cellular defects that might underlie the neuronal connectivity defects in autism.

This research will use innovative techniques for exploring the role of alpha-chimaerins in autism and the findings could lead to research into potential treatments or prevention of the disorder.

Mentor: Philip Washbourne, Ph.D. 
University of Oregon
Post-doctoral Fellow: Thomas Pietri, Ph.D.

The role of cell adhesion molecular in synaptogenesis in vivo

A current hypothesis for the etiology of autism and other related pervasive disorders points to deficits in the formation of cell to cell contacts during development leading to an imbalance in the triggers that turn cells on and turn cells off.

Proper brain development requires precise control of this process to create and maintain complex adult neural networks that can manage multiple types of information at once. Two of the crucial signals which initiate and maintain these neural networks and circuits are called Synaptic cell adhesion molecule (SynCAM) and neuroligin.

While previous research supported the importance of Neuroligin and SynCAM in the formation of synapses (biochemical connections between nerve cells), their role in the development of the nervous system has not been well studied or understood. Drs. Washbourne and Pietri will use the zebrafish model to study how neuroligin and SynCAM participate in formation of functional synapses both during development and a behavioral test in the zebrafish called the “touch task”.

This test evaluates a motor behavior in response to a sensory stimulus and requires the correct function of both connections which turn on and turn off neuron activity.

What this means for people with autism: Independent research has demonstrated that mutations of the neuroligin protein are associated with autism spectrum disorders. This proposal will examine the role of neuroligin and a similar protein, SynCAM, in the development, maintenance, and plasticity of neuronal processes in the brain, notably in respect to changes in neuronal activity.

The importance of these two molecules in brain development and connection of neurons can be translated into clinical interventions to directly alter the course of autism spectrum developmental disorders.

Mentor: John Welsh, Ph.D.
Oregon Health Science University
Pre-doctoral Fellow: Paulo Rodrigues

Neurophysiology Training in Autism Research: Basic to Clinical

Using sensitive electrophysiological measures, previous research has found that children with autism do not respond properly to sounds repeated in succession. This finding has profound implications for how such children process verbal communication during critical periods of social and language development.

This research will develop a set of electrophysiological measures that can be used to directly compare brain activity in children with autism with brain activity observed in animal models. In the process, it will train a pre-doctoral fellow to bridge the gap between the basic and clinical neuroscience in autism research.The fellow will primarily focus on recording of electrical activity in the rat auditory cortex during rapid processing of auditory sounds.

He will also work with Dr. Timothy Roberts at Children’s Hospital in Philadelphia, observing children with autism performing the same tasks while being measured with magnetoencephalography (MEG). This will allow him to relate measurements in rats directly to activities of the primary auditory cortex in children with autism.

What this means for people with autism: Findings from these experiments will allow researchers to relate invasive electrophysiological recordings in the rodent brain to noninvasive magnetoencephalographic recordings in children with diagnoses of autism spectrum disorders.

Providing an interdisciplinary research environment will allow Mr. Rodrigues exposure to a research training environment which will stress the need for translating animal models to human diseases.

Mentor: Xinyu Zhao, Ph.D. 
University of New Mexico
Post-doctoral Fellow: Jinfeng Bao, Ph.D.

MBD1 regulation of anxiety and autism

Dr. Zhao’s laboratory has developed a mouse deficient in the epigenetic gene expression regulator MBD1, which is critical for the functioning of brain regions, such as the amygdala and hippocampus, which are highly involved in autism. These mice show normal prenatal development, but after birth have characteristics similar to individuals with autism, such as impaired learning, increased anxiety, abnormal brain serotonin activity, and deficient hypothalamic-pituitary-adrenal (HPA) axis function.

While genetic regulation is crucial for early development and postnatal brain function, many environmental factors (e.g., pollution, diet) can cause changes in genetic expression without altering the DNA code.

The proposed research will determine the usefulness of the MBD1 mutant mouse as an animal model of autism, and the role of MBD1 in regulating the serotonin system and HPA axis. In addition, the investigators will examine whether currently available medication to treat autism, in conjunction with dietary methyl-donor supplementation, can correct the traits that MBD1 mutant mice share with autistic individuals.

What this means for people with autism: The development of an animal model of autism will advance research on the molecular and cellular basis of autism. The investigators are looking for a link between environmental modulators and such neural developmental disorders, and specifically they seek to determine how anxiety and stress are regulated at epigenetic levels and the relationship of this regulation to the etiology of autism.

Brain structure and function in autism spectrum disorders

Mentor: Huda Zoghbi, M.D.
Baylor College of Medicine/Howard Hughes Medical Center, Houston, TX
Pre-doctoral Fellow: Rodney Samaco

Consequences of MeCP2 Deficiency in the Serotonergic System in Autism Spectrum Disorders

One way researchers can investigate a complex, multi-gene disorder such as autism is to use what is known about related disorders to see if the same mechanisms might be involved. Rett syndrome (RTT) is one of those disorders related to autism. In fact, it’s the only disorder among the many classified as autism spectrum disorders (ASDs) with a known genetic cause. Specifically, mutations in a gene responsible for the protein, methyl-CpG binding protein 2 (MeCP2), cause RTT.

While it is still unclear how MeCP2 relates to the behavioral impairments characteristic of RTT, a possible explanation is that MeCP2 plays a critical role in particular neurons. One potential group of neurons that influence the kind of behaviors shared by RTT and autism are the serotonergic neurons, which use serotonin to communicate to other neurons to mediate specific aspects of behavior.

In order to investigate the role of MeCP2 on serotonergic neurons, the fellow and Dr. Zoghbi will remove MeCP2 from serotonergic neurons in mice and use behavioral analysis of these mice to examine anxiety levels and social withdrawal. They will also use a novel approach called “BACarray” technology to generate mice that will be used to identify genes that are inappropriately expressed in serotonergic neurons in the absence of MeCP2. These genes will be good candidates for further study on their possible role in autism spectrum disorders.

What this means for people with autism: These studies will help pinpoint specific behavioral characteristics associated with the absence of normal MeCP2 function in serotonergic neurons.

This work may serve as a solid foundation for pre-clinical trials that involve targets of MeCP2 function and expedite the rational design of therapies for these disorders. Dr. Zoghbi’s lab was instrumental in discovering that mutations of the MeCP2 gene led to Rett Syndrome, and brings important expertise and a strong training environment for the fellow to the field of autism research. 

Mentor: Anthony Bailey, B.Sc., M.B.B.S., F.R.C.Psych, DCH
University of Oxford, United Kingdom 
Post-doctoral Fellow: Simon Wallace, Ph.D.

A Developmental Magnetoencephalographic Study of Face Processing in Autism Spectrum Disorders

Research finds that people with autism spend less time looking at other people’s faces and they have problems reading emotions from facial expressions. This indicates that they do not develop typical face processing abilities.

In this study, post-doctoral fellow Simon Wallace will use magnetoencephalography (MEG) to non-invasively measure brain activity in children with autism during two different face processing tasks. Children from different ages will be examined to better understand the development of the neural circuits that are responsible for face processing. In addition, using MEG, specific neurophysiological “markers” can be identified which are sensitive to facial expression.

Understanding how the brain mechanisms used to process faces changes over the age span will allow researchers to identify developmental transitions when therapeutic interventions would be most beneficial.

Dr. Wallace is an ideal candidate for this fellowship, having conducted research and published articles on face recognition during graduate school. In particular, for his Ph.D. thesis he developed computerized tests of face expertise and sensitivity to eye gaze direction, which will be used in this study.

What this means for people with autism: This study will allow researchers to specifically map the development of neural pathways used both by typically developing children and children with autism, across the full range of development. It will provide insight into impairments in the ability of people with autism to process social cues provided by faces. Findings could lead to interventions targeted to specific developmental stages when the face processing system is particularly receptive to change.

Mentor: YuhNung Jan, Ph.D.
University of California, San Francisco
Fellow: Quan Yuan, Ph.D.

Drosophila as a Model System for Identifying Molecular Mechanisms Underlying Dendrite Development and Possibly Autism

Researchers have proposed that a malfunction during brain development when neurons are growing and forming connections with other nerve cells is an underlying cause of autism. In particular, there appears to be impairments in the growth of dendrites—branch-like protrusions the neurons use to form connections with other nerve cells.

Defects in dendrite development can lead to abnormal neural connectivity, which reduces the nervous system’s ability to function properly. Although a leading theory of autism, this hypothesis needs to be tested at the cellular, molecular and genetic level.

Dr. Jan and post-doctoral fellow Quan Yuan plan to study dendrite development in Drosophila—the common fruit fly. Drosophila is a useful system for studying brain development and function because of its simplicity. In fact, researchers can attach molecular markers onto the dendrites of specific neurons and monitor their growth during development.

Drs. Jan and Quan will examine the regulation of dendrite development and how abnormal development affects brain function and fly behavior. To do this, they will screen large numbers of Drosophila to find fly mutants with defects in various aspects of dendrite development. They will then use these mutants and state-of-the art genetic techniques to examine the functional consequence of abnormal dendrite development at defined development stages and in specific tissues. Genes identified in these studies could in turn be used to screen for candidate genes for autism in humans.

Implications: Findings from this research will demonstrate how defects in the ability of neurons to form connections can influence brain function as well as behavior. It will also establish a vital animal model for studying the brain defects in autism and will help identify underlying genetic components of autism spectrum disorders.

Mentor: Susan Bookheimer, Ph.D.
University of California at Los Angeles
Pre-doctoral Fellow: Ashley Scott

Neural Basis of Reward Systems in Children with Autism

This project will investigate the basal ganglia in autism, specifically reward and implicit learning systems, using functional and structural magnetic resonance imaging (MRI).

Brain regions within the basal ganglia in the brain, including the ventral striatum and nucleus accumbens, are involved in motor learning and the processing of rewards. Therefore, disruption of this system could account for several core features of autism such as motor stereotypies, rigidity in learning and poor response to normally rewarding stimuli such as facial affect.Using established tasks which test reward learning, Dr. Bookheimer and Ms. Scott will determine if children with autism have a deficit in basal ganglia function in response to rewards. In addition, the size of subregions within the basal ganglia, including the nucleus accumbens, caudate and putamen will also be measured.

Finally, the correlation between the activity and size of these regions and degree of functional impairment will be calculated. This project will relate the structural and functional findings to autism symptomatology, specifically measures of repetitive behaviors, restricted interest, language, and overall severity of autistic symptoms. This project will expose the trainee to multiple research methods and provide a comprehensive introduction into responsible conduct of autism research.

What this means for people with autism: This proposal will address key questions in the investigation of the underlying neurobiology of autism by examining a system implicated motor behavior, learning and reward processing, as well as provide training in the skills necessary to pursue an academic career in neuroimaging and autism research for the trainee.

Mentor: Janet Lainhart, M.D.
University of Utah
Pre-doctoral Fellow: Molly DuBray

The Neuropathological Basis of Variation in Intelligence in Autism

Although IQ varies widely among people with autism, researchers have yet to figure out what causes this variation. However, several lines of research have found abnormalities in the area of the brain called the corpus callosum in people with autism and preliminary findings from Dr. Lainhart’s laboratory indicate that these abnormalities may be related to IQ in people with autism.

This study will expand on that preliminary work, using anatomical magnetic resonance imaging (aMRI) and diffusion tensor MRI to measure brain volume and the integrity and strength of the connections between nerve cells in the corpus callosum. Pre-doctoral fellow Molly DuBray, who brings to the fellowship strong experience in statistics and previous work with brain imaging, will compare data from a large number of individuals with autism and those who are not affected. In the process of this study,

What this means for people with autism: Findings of a relationship between abnormalities in the corpus callosum and cognitive behavior in people with autism could suggest new treatments that help strengthen the connections in this brain area. 

Mentor: Laurent Mottron, M.D., Ph.D.
University of Montréal, Canada
Post-doctoral Fellow: Kate O’Connor, Ph.D.

Investigation of Lateral Inhibition Hypothesis in Autistic Visual System

Individuals with autism show interesting abilities in visual processing abilities. Spatial information processing is the same or even enhanced compared to typically developing individuals, while ability to take in the whole scene is impaired. This is consistent with other research that suggests that individuals with autism attend more to the parts or elements of a picture rather than combining information from multiple parts of that scene.

Based on their past research, Dr. Mottron suggests that an atypical neural system in a specific area of the visual cortex in those affected with autism has the consequence of enhancing some abilities while compromising others.These investigators will study a specific neural network called “lateral inhibition”.

Using behavioral assessments, Drs. Mottron and Bertone can study how neurons which connect different parts of the brain with the visual cortex function. In addition, he will investigate the idea that experience-dependent changes in neuronal connections may explain the differing abilities in visual processing.

What this means for people with autism: This study will test a novel theory of neural connectivity patterns that affect how people with autism process visual information. The findings will provide information about how the visual cortex develops in people with autism and will provide insight into how abnormalities in visual processing may affect socially-relevant behavior such as perceiving faces.

Mentor: Charles Nelson, Ph.D.
Harvard Medical School, Boston
Post-doctoral Fellow: Shafali Jeste, M.D.

Electrophysiological and Behavioral Investigations of Social-Emotional Integration in Young Children with Autism

One of the hallmark symptoms of autism is a difficulty in social communication. This symptom may be traced to the difficulty in processing social and emotional information, and responding to emotional cues in faces. Impairments in processing emotional signals from social scenes have been linked to differences in brain activity areas of the brain including the fusiform face gyrus, the amygdala and the cerebellum.

These observations have led researchers to predict that typically developing children utilize theses brain regions concurrently to process emotional faces and emotional voices, while children with autism do not. If this is true, then it may help explain why children with autism pay less attention to other people’s emotional expressions and have difficulty understanding them.

Postdoctoral fellow Joseph McCleery, in collaboration with Dr. Nelson and his colleagues, will test this theory by examining brainwave activity measured as event-related potentials (ERPs), while children process matching and mismatching happy and fearful faces and voices. They will also study the children’s behavioral responses to the emotional expressions of others in order to better understand how measures of brain activity during social information processing relate to social and emotional behavior.

What this means for people with autism: Joseph McCleery brings extensive experience in electrophysiological testing to this research project. This is a new area of investigation that holds promise for providing a common paradigm for researchers to better understand and characterize the neural mechanisms of one of the core symptoms of autism.

Mentor: Kevin Pelphrey, Ph.D.
Duke University
Pre-doctoral Fellow: Elizabeth Carter

Functional Neuroimaging in Children with Autism

This research project will build on current Autism Speaks funding by bringing on a graduate student who brings both clinical training from Yale Child Study Center and imaging experience from the University of California at San Diego. Dr. Pelphrey and Ms. Carter will be examining brain activity during joint attention tasks in children with autism. Joint attention and deficits in eye gaze are two hallmarks of what is termed “Social perception”.

People with autism demonstrate striking abnormalities in social perception. Researchers have just begun to illustrate and explain the neural systems involved in aspects of social perception which are controlled by the “social brain”, and what the social brain looks like in individuals with autism is poorly understood. In order to better characterize the neural circuitry behind eye gaze and joint attention, children with autism and those not affected will be presented with a novel virtual reality paradigm during a functional MRI assessment to evaluate which brain areas participate in these tasks.

What this means for people with autism: This research will help identify the specific neurophysiological mechanisms involved in social perception, leading to an improved evaluation of novel therapeutic interventions. In addition, this and other research on social perception development in autism will help develop new treatment models that traditionally are skill-based to focus more on teaching children with autism to monitor gaze, identify emotions, and infer the intentions of others.

Mentor: Susan Rivera, Ph.D. 
University of California at Davis
Pre-doctoral Fellow: Kami Koldewyn

Biological Motion Perception in Autism: A window into social cognition deficits? 

Dr. Rivera and her colleagues at the University of California at Davis will study the function of a pathway of the visual system called the “dorsal stream” in adolescents with autism. This pathway is considered important for the development of normal biological motion perception. In particular, preliminary results have shown that individuals with autism are able to see moving dots on a screen. However, when the dots of light are synchronized to mimic motion of a face, person or animal, individuals with autism show an impairment in the ability to recognize this biological motion. 

The mentor and her fellow will take advantage of functional MRI technology to assess which brain areas are not activated properly during this biological motion task. The task will include both biological motion mimicking individuals, or more than one “person” interacting with each other. Multiple brain regions will be assessed and compared to individuals of the same age who are not affected with autism. 

What this means for people with autism: This project will bring in experts in visual neuroscience and give the fellow and mentor the opportunity to present their ideas to groups of researchers who are not familiar with autism research. Biological motion processing may be a building block of social perception, which is one of the hallmark symptoms of autism spectrum disorder.

Mentor: Timothy Roberts, Ph.D.
The Children’s Hospital of Philadelphia, Pennsylvania
Post-doctoral Fellow: Marc Egeth Ph.D.

Electrophysiological Endophenotypes of Autism: Magnetoencephalographic Investigations 

Ongoing collaborations between Drs. Roberts and John Welsh at Oregon Health Sciences University have identified role for an “intermediate phenotype” of autism. This intermediate phenotype is an objective and quantifiable measure of function that will be able to better integrate experimental models and characteristics found in the clinical population. The current research project builds on previous Autism Speaks funded research which uses non-invasive magnetoencephalographic recordings to examine the ‘electrical brain signatures’ of children with diagnoses of autism spectrum disorders. To expand on this research, Dr. Egeth will be working in both a clinical population mentored by Dr. Roberts and an experimental model mentored by Dr. John Welsh. 

Children with autism spectrum disorders will be monitored to determine how different brain regions respond to auditory signals. The ability to behaviorally respond to different sound tones will be linked to a change in brainwave activity. Of interest, a particular feature of brainwave activity, called the “neocortical gamma rhythm” will be studied. These studies will be compared to electrical activity in the brains of on animal model using a selective attention paradigm. 

What this means for people with autism: The use of electrophysiological techniques will enable the identification of a neuronal signature or phenotype. This will provide a better understanding of the relationship between the clinical picture of autism (such as the behaviors) and electrophysiological brain signatures. 

Mentor: Lisa Boulanger, Ph.D.
University of California San Diego 
Post-doctoral Fellow: Lawrence Fourgeaud, Ph.D.

Modulation of Glutamate Receptor Trafficking in Autism: Role of MHC class I

There is growing evidence of an imbalance in neuronal signaling in the brains of some individuals with autism. The neurotransmitter glutamate is an important chemical that “turns on” neurons. Direct measures of glutamate neurotransmission have been used to measure proper neuronal signaling in animal models.

Recent studies have linked the ability of neurons to respond to the neurochemical glutamate to the changes in immune response. Because maternal immune challenge during pregnancy may be a risk factor for autism in children, this raises the possibility that maternal immune challenge may alter glutamatergic neurotransmission.

This is may be accomplished through modification of MHC class I molecules (major histocompatibility complex class I) in the developing fetal brain. MHC-I molecules are an essential part of the immune response which are now known to be expressed in the brain and modulate neuronal function.Using a mouse model, Drs. Boulanger and Fourgeaud will test whether changes in MHC class I in the developing brain effects glutamate receptors, and whether these changes can be induced in the fetal brain by maternal immune challenge. Together with the projects mentored by Dr. McAllister and Dr. Patterson, the role of alterations in immune function on brain development and later behavioral function will be better understood.

What it means for people with autism: These studies could also provide a mechanistic link between maternal immune challenge, a significant environmental risk factor for autism, and glutamatergic dysfunction, a hallmark symptom of this disorder. Furthermore, the results of these studies may suggest new, immune-based strategies for the diagnosis, treatment, and prevention of autism.

Immune system function

Mentor: Kimberley McAllister, Ph.D.
University of California, Davis
Pre-doctoral Fellow: Marian Wampler

The role of MHC class I molecules in synapse formation: possible implications for the pathogenesis of autism

Although there is a strong genetic component to autism and autism spectrum disorder, there are non-genetic causal factors. Maternal viral infection has been put forward as one such factor. During an infection, the immune system releases molecules called cytokines which then trigger an increase in MHC-I molecules.

Dr MacAllister’s team has previously shown that altered MHC-I levels can affect the brain by reducing the ability of neurons to form synapses and modifying existing connections. Therefore, it is possible that modifications of immune function may alter normal brain development and possibly produce symptoms of ASD.

This new research will investigate the specific role of cytokines on MHC-I expression and how these changes affect neuronal development. This will be done by measuring MHC-I levels after administration of cytokines as well as examining the number of synapses following exposure. Finally, the function of these neuronal connections will be tested to determine whether the immune response, possibly altered in autism, leads to impaired connectivity and circuitry.

What this means for people with autism: Changes in immune system function have been reported in individuals with autism, but the consequences of this hyperactivity on brain development are not yet well understood. These studies will lead to a better understanding of the neurobiological consequences of altered immune activity, and how they relate to ASD.

Mentor: Paul Patterson, Ph.D.
California Institute of Technology
Pre-doctoral Fellow: Stephen Smith

Role of Cytokines in Mediating the Effects of Maternal Immune Activation on the Fetal Brain

Children whose mothers develop infections during pregnancy are at increased risk for autism, schizophrenia or other neurodevelopmental disorders. However the molecular pathway that leads from infection to autism is unclear.

Using an animal model of maternal viral infection, Dr. Patterson have shown that the maternal immune reaction, rather than the virus itself, interferes with fetal development leading to behavioral symptoms of heightened anxiety and decreased social interaction

.This experiment will establish which specific immune factors interfere with fetal brain development. Four different immune factors will be tested to produce and then reverse early behavioral deficits in offspring exposed in utero to these immune factors. Any immune factor that meets both criteria will be a leading candidate for continued research into specific molecular pathways that interfere with normal development and lead to autism-like symptoms.

What this means for people with autism: This project will use a mouse model of a known risk factor for autism—maternal viral infection—to determine a mechanism that elicits changes in fetal brain development and leads to the autistic phenotype. These findings could lead to a better understanding of what goes wrong in autism, and suggest potential methods of preventing the disorder.

Intervention and treatment of children with ASD

Mentor: Susan Bryson, Ph.D.
IWK Health Centre/Dalhousie University, Canada
Fellow: Jamesie Coolican

Brief Training in Pivotal Response Treatment for Parents of Children Newly Diagnosed with Autism Spectrum Disorder

Early diagnosis and early treatment for autism spectrum disorders is critical to ensuring the best outcome for children with this potentially devastating disorder. A key to making early treatment available to families of different means and treatment access is to provide a treatment that is easy and inexpensive to implement.

One treatment that shows promise is Pivotal Response Treatment (PRT), which targets the development of social-communication and other functional skills. Treatment outcome research has found that PRT is effective at promoting language development, increasing socialization and decreasing disruptive behaviors in children with autism.

This study will evaluate whether training parents in PRT can be an effective line of treatment for children newly diagnosed with autism who are awaiting, or unable to access, more comprehensive treatment. Participating parents will receive three two-hour sessions of intensive individual training in PRT techniques.

Ms. Coolican will evaluate the intervention at the end of the training period and again three months post-training. The study will measure treatment outcome through parent reports and direct observation of child communication skills, positive affect and disruptive behaviors, and will also evaluate whether the treatment has been implemented properly throughout the study period.

What this means for people with autism: Evidence that brief parent training in PRT is effective promises to provide an immediate, cost-effective intervention that could be adopted widely in rural and urban centers alike, and extended to others involved in the care and education of children with autism, including teachers and childcare providers.

Mentor. Justine Cassell, Ph.D.
Northwestern University, Illinois
Pre-doctoral Fellow: Bennett Leventhal, M.D.

An Authorable Virtual Peer for Children with Autism Spectrum Disorder

Children with Autism Spectrum Disorder (ASD) often have difficulties with communication and reciprocal social interaction skills (for example difficulties in being able to have a friend or engaging in interactive conversations). In her previous research, Professor Cassell developed a technology called ‘Virtual Peers’ – life-size 3D animated characters that look like children and are capable of interacting, sharing real toys, and responding to children’s input.

For typically developing children, Professor Cassell showed that ‘Virtual Peers’ can help increase children’s emerging literacy and social behaviors and real life social interactions. So under Professor Cassell’s guidance, Dr Leventhal plans to design and evaluate a computer system that allows children with ASD to interact with a life-size ‘Authorable Virtual Peer’.

This computer system will test children with ASD to determine whether engaging them on narrative task with a ‘virtual partner’ (whom they themselves can program) can, for example, help practice taking turns, and whether the children through creating and controlling how the virtual peer communicates, will develop a better understanding of putting together their own communications and reciprocal social interactions.

What this means to individuals with autism: The study may provide important information about the underlying mechanisms of communication and social reciprocity in ASD and provide an innovative intervention.

Mentor: Tony Charman, Ph.D.
University College London
Fellow: Sally Clifford, Ph.D.

Further Development of the COSMIC as a Measure of the Generalization of Treatment Efficacy in the PACT Study.

There is general consensus among members of the autism research and treatment communities that treatment for autism spectrum disorders should focus on improving social interactions and communication skills.

Dr. Charman and his colleagues have used a test called the Classroom Observation Schedule to Measure Intentional Communication (COSMIC) as a way to measure communication ability.

Researchers watch a videotape of children in a real-life setting such as the classroom targeting interaction of children, their peers and their teachers. In this study, the COSMIC will be integrated into an ongoing trial called the Preschool Autism Communication Trial (PACT).PACT, as originally funded, has no evaluation of social and communication behavior in an everyday situation.

This study will fund post-doctoral fellow Sally Clifford to use COSMIC to evaluate a subgroup of 48 PACT participants in two everyday school activities: one in the classroom interacting with a teacher and one on the playground interacting with peers. Her findings will provide support for any improvements found from other outcome measures of the PACT study and will help validate COSMIC as a tool for future treatment outcome studies.

What this means for people with autism: This study will add a critical outcome measure to one of the largest ever randomized clinical trials of the psychosocial behavioral treatment for autism. Specifically, it will provide information about how a treatment to improve social and communication skills in children with autism translates into the real world. 

Screening and diagnosis in a high risk population

Mentor: Katarzyna Chawarska
Yale University School of Medicine
Pre-doctoral Fellow: Frederick Shic

Computational Modeling of Visual Attention in Young Children with Autism Spectrum Disorders

Recent research using eye-tracking technology suggests that people with autism spectrum disorder (ASD) focus their gaze on the mouth and body rather than on the eyes of faces in a visual scene.

These scanning patterns have been found to correlate with measures of social dysfunction. Therefore, characterizing and quantifying differences in how children with autism attend to different stimuli in a social scene can illuminate underlying (and harder to measure) deficits in social-cognitive functioning. Utilization of eye-tracking technology provides promise in better diagnostic and measurement techniques.In order to better describe patterns in eye gaze and visual processing in children with autism, the contextual cues in a social scene will be altered and gaze patterns measured. This includes changing the orientation of faces in a movie or turning the sound on and off.

Eye gaze patterns will be measured while watching these videos to compute how individuals perceive and understand that scene under normal and disturbed conditions. The ultimate goal is to build a developmental model of visual preferences in those with and without autism, to better understand how these particular preferences lead to social dysfunction.

What this means for people with autism: This is a unique opportunity for an engineer and student of computational modeling to bring methods and expertise to the Yale Child Study Center. The findings from this study will help pinpoint the underlying cause of specific differences in visual behaviors in people with autism and how those differences may lead to social deficits. In addition, this work could lead to new automated diagnoses of ASD based on computational analyses of gaze.

Mentor: Mark Johnson, Ph.D.
Birkbeck College, University of London, United Kingdom
Post-doctoral Fellow: Atsushi Senju, Ph.D.

Face- and Eye-Contact-Detection in Infants at High Risk for Autism Spectrum Disorders

Research has begun to establish that infants who are eventually diagnosed with autism show early deficits in their ability to orient to faces and to follow another person’s gaze. Dr. Johnson has proposed that the same brain circuits that control these infant behaviors may be involved in later social development.

Post-doctoral fellow Atsushi Senju will join Dr. Johnson and his team in a study designed to examine face detection and gaze in infants who have a family history of autism and are at a high risk for later diagnosis. The researchers will use standard behavioral techniques to measure length of gaze and face detection in the infants. In addition, they will use a non-invasive method of measuring electrical activity in the brain to measure event related potentials.

This will allow Dr. Johnson and Dr. Senju to gauge activity in the brain circuits thought to control face/gaze detection. They will compare high-risk infants to a group of infants at low risk for developing autism, looking for differences that could lead to a method for early detection of autism.

What this means for people with autism: This project is one of the first studies to examine the electrophysiological markers in sub-cortical regions during a face and gaze detection task in infants at risk for developing autism. Since this network is thought to play a critical role in the development of social cognition in the earliest period of life, this project promises to further enhance the understanding of the atypical development of the social brain network in infants who will later be diagnosed with ASD. 

Role of genes and the environment on ASD

Mentor: Francesca Happe, Ph.D.
King’s College, London, United Kingdom
Fellow: Angelica Ronald, Ph.D.

From Genes to Brain to Behavior: A Multidisciplinary Investigation of the Autistic Triad

Most research on autism spectrum disorders (ASDs) has assumed that the three core behaviors that represent ASDs—social impairments, communication, and restricted/repetitive behaviors – the “triad” are interrelated. However, it is possible that these three domains may be very different and caused by different mechanisms. This implies that different features of autism may be caused by different genes, associated with different brain regions and related to different core cognitive impairments. Dr. Happe and her colleagues, therefore propose that research is likely to learn more about ASDs by examining each of these behaviors separately.

Dr. Angelica Ronald, the post-doctoral fellow, will conduct new analyses to examine individual differences in affected and non-affected people in three domains of cognitive processing. She will also identify genetic markers and environmental factors which are associated with each core behavior.

This will help better identify the causes for each symptom of autism, and determine if they can be separated from one another. Data and resources from the Twins Early Development Study, will be used to expedite findings. The post-doctoral fellow is well qualified for this project, having already published several papers on autism research and recently received the 2006 Young Investigator Award by the International Society for Autism Research.

What this means for people with autism: This research will take a novel approach to studying the gene-brain-behavior pathways in ASDs by examining the three core behavioral traits of ASD separately. If the theory holds up and different features of autism are caused by different genes, associated with different brain regions, and related to different core cognitive impairments, the findings from this study may lead to tailored interventions designed to address specific characteristics of each behavioral trait.

Mentor: Edwin Cook, M.D.
University of Illinois at Chicago, IL
Fellow: Camille Wilson Brune, Ph.D.

Phenotypic Constellation of Autism Associated Variants

Current consensus on autism genetics is that multiple genes are likely to be involved. It is possible that different autistic individuals could harbor different combinations of affected genes, leading to variations in clinical presentation, including nature and severity of deficits.

In this study, Dr. Cook and his colleagues will try to establish correlation between known genotypes with specific phenotypes, which could help define autistic subtypes. In addition, by exploring gene-gene interaction, Dr. Brune hopes to associate specific combinations of genotypes with increased risk for autism.

What this means for people with autism: A better understanding of how genetic variations contribute to autism risk as well as different phenotypes would facilitate the identification of autism subtypes which could impact treatment selection.

Mentor: Arnold Kriegstein, M.D. Ph.D.
University of California at San Francisco, CA
Fellow: Ashkan Javaherian, Ph.D.

Converging Molecular Pathways in Autism Spectrum Disorders

Fragile X and Tuber Sclerosis are two known single gene heritable developmental disorders that can cause autism or autism-like presentation in affected individuals. One way to better understand the disease mechanism, specifically, the biological pathway that a single mutation can lead to the observed autistic phenotype could spur further gene discovery, and more important, identify additional molecular targets suitable for drug intervention.

Dr. Kriegstein and his postdoctoral fellow, Dr. Ashkan Javaherian, propose to analyze in detail the molecular pathways of both the Fragile X Mental Retardation gene (FMR) and the Tuberous Sclerosis Complex to (TSC) explore possible common proteins and converging or shared functions that may be relevant to autism.

What this means for people with autism: This innovative study offers a new approach to examine molecular pathways in brain development that could lead to autism. The identification of a single molecular pathway common to both disorders could pinpoint lead to an attractive candidate pathway for the development of targeted intervention.

Mentor: Gary Rudnick, Ph.D.
Yale University School of Medicine, CT
Fellow: Sotiria Tavoulari, Ph.D.

The N-terminus of serotonin transporter: a role in regulation

Many studies have suggested a link between autism and the serotonin system. In addition to elevated blood serotonin level in autistic individuals and the association of increased stereotyped behavior with reduction in ventral nervous system serotonin, many affected individuals treated with SSRI (Prozac-related medications) have shown a reduction in aggression and ritualistic behavior.

Dr. Rudnick and his postdoctoral fellow, Dr. Sotiria Tavoulari, plan to test the biological properties of specific mutations in the serotonin transporter gene, especially the Gly-56 at the end of the molecule that have been implicated in increased transporter protein function that may result in aggravation of autistic symptoms.

What this means for people with autism: Findings from this study could further elucidate the mechanism of serotonin system’s association with autism, which could lead to improved psychopharmacological intervention, especially with the many drugs targeting this system already available for other indications.

Mentor: William McMahon, M.D.
University of Utah, Utah
Fellow: Michele Villalobos

Neurocognitive Phenotypes in the Genetics of Autism

One of the major obstacles for autism genetics research is heterogeneity: extensive variations in clinical presentation make it difficult for investigators to correlate genetics findings with heterogeneously presented symptoms. By looking at traits in unaffected family members that are not autism but are associated with autism, however, scientists might be able find ways to lessen the complexity of the genetic analysis.

Michel Villalobos, Dr. Mahon’s fellow, will work with Dr. McMahon to examine variables related to intellectual functioning, language ability, sex, and ASD characteristics in autistic individuals and their unaffected family members.

It is hoped that analyzing these neurocognitive variables using the rich and unique Autism Speaks-funded Autism Genome Project linkage data (AGP phase 1) could help define subtypes to further reduce analytic complexity and gene identification.

What this means for people with autism: This project will leverage a rich, unique dataset generated by the AGP to explore new approaches in autism gene discovery. If successful, findings from this study could speed gene identification and shed light on the complex relationship between autism genotype and phenotype.

Mentor: Peter Penzes, Ph.D. 
Northwestern University, Illinois
Postdoctoral Fellow: Huzefa Photowala, Ph.D.

Molecular mechanisms of aberrant synaptogenesis 

Genetic studies in autism have linked genes which encode synaptic adhesion molecules to autism. The proper expression of these genes control how neurons form new connections with each other as well as strengthen existing connections, a process called “synaptogenesis”.

Together with neuropathological evidence which indicates deficits in neuronal signaling in autism, an abnormality in synaptogenesis may underlie many behavioral and neuroanatomical features of autism. As both genetic and environmental influences have been implicated in the cause of autism, it is important to understand how these factors influence synaptogenesis independently and how they may interact. Dr. Penzes will apply his expertise as a neurobiologist to study the interaction of two molecules which control synaptogenesis, called ephrin and Eph, interact with one another and how they are influenced by environmental stimulation.

What this means for people with autism: Dr. Penzes’s laboratory has identified one of the few known molecular mechanisms to regulate dendritic spine density. As such, the interaction of these pathways is a promising candidate for understanding the etiology of autism on a cellular level. Most important, if Dr. Penzes and colleagues are able to demonstrate inhibition of these pathways by drugs, this would represent a treatment that could potentially prevent or mitigate the effects of autism. 

Mentor: Pasko Rakic, M.D., Ph.D.
Yale University School of Medicine 
Post-doctoral Fellow: Xiuxin Liu, M.D., Ph.D.

Effect of a non-steroidal anti-inflammatory drug (NSAID) on neuronal migration

While the precise causes of autism is not yet known, multiple genetic and environmental factors are thought to play an important impact on the development of the disorder. The site where certain neurons connect, called gap junctions, are sensitive to environmental agents and have downstream effects on cell growth and reproduction, and possibly on migration of neuronal precursors to their appropriate destinations.

In order to manipulate the function of the gap junction in an animal model, the investigators will test the effects of an NSAID which alters the function of gap junctions on the activity of neurons during development and migration. Deficits in neuronal migration and formation of different layers of the cortex may lead to the neuropathological and behavioral features observed by other scientists.

The mentor and the fellow will use advanced molecular biology techniques to trace the position of the migrated neurons during critical periods of neuronal development. They will also study properties of the misplaced neurons to determine their abilities to participate in a functional network.

Finally, behavioral analysis of offspring exposed to prenatal NSAIDS will be performed. This will help better link any neurobiological differences with functional outcomes, especially as they relate to the symptoms of autism spectrum disorder.

What this means for people with autism: Using disruption of the gap junction by biophysical and environmental factors will help identify the cause of cortical malformation. This will be relevant to a better understanding of brain development as well as the causes of autism spectrum disorders. 

Mentor: Susan Santangelo, Ph.D.
Harvard Medical School, Boston
Pre-doctoral Fellow: Shun-Chiao Chang

Association of Distal-less Homeobox (DLX) Genes and Autism: Independent and Interactive Effects of Single SNPs and Haplotypes

Several lines of research indicate that a family of genes called Distal-less Homeobox (DLX) genes may be important in autism spectrum disorders (ASDs). 

These genes encode transcription factors which are necessary for the process of reading the DNA code into synthesis of proteins. Mutations of DLX genes have been associated with autism spectrum disorders, and are important in the development of brain regions such as the amygdala which have been implicated in the neuropathology and behavioral features of ASD.

This pre-doctoral fellowship will allow Ms. Chang to apply her experience in the molecular epidemiology of cancer to autism research by investigating the role of all 6 genes in DLX family in ASD. She and Dr. Santangelo will use genetic information collected from over 550 families available through the Autism Genetic Research Exchange (AGRE) repository.

Using state-of-the-art genetic scanning techniques to analyze the chromosomal regions containing all six DLX genes together, identification of risk alleles and gene-gene interactions can be studied. By thoroughly characterizing common genetic variation in the DLX gene family, the researchers can provide a better understanding of the potential influence of DLX genes on autism risk.

What this means for people with autism: This study provides a solid training plan to provide the fellow experience to continue a career in autism research. The study will enrich the understanding of the role of these genes in autism spectrum disorders, including how genes interact with each other to produce symptoms of ASD.

Mentor: Nenad Sestan, M.D., Ph.D.
Yale University School of Medicine
Post-doctoral Fellow: Mladen-Roko Rasin, Ph.D.

Role of a Cell Adhesion Molecule in Cortical Minicolumns

Neuropathological research in autism spectrum disorders has identified a disruption of the organization of neurons in the cortex. This is evidence by small, tightly packed neurons which are abnormally close to one another. They form patters called “minicolumns” which are named this since the cells form a vertical column bundled together. Cortical minicolumns appear to be important for neural processing, integrating sensory signals and generally coordinating signals in the brain’s cortex—all functions that could be related back to symptoms of autism.

Dr. Rakic will be investigating possible pharmacological manipulation of cortical development. On the other hand, Dr. Sestan and his research team will study the role of e-cadherin, a cell adhesion molecule, which may be important to the formation of cortical minicolumns. Using a mouse model which lacks e-cadherin, this group will examine whether these mice show anatomical, functional, and behavioral symptoms relevant to autism spectrum disorders.

Finally, together with the department of neurogenetics, mutations of the e-cadherin gene will be examined in families with autism.

What this means for people with autism: This is an interdisciplinary project which will help better explain the neuropathological features of autism. This research lead to a better understanding of a potential role of synaptic adhesion molecule expression on neuroanatomical and neuropathological findings which will better explain the causes of autism spectrum disorders.

Language, cognition and repetitive behaviors

Mentor: Boutheïna Jemel, Ph.D.
Rivière des Prairies Hospital / Fernand Seguin Research Center
Post-doctoral Fellow: Isabelle Soulières, Ph.D.

Investigation of interactions between processing levels via categorization processes

Children with autism have been shown to show differences in the ability to categorize information and process novel stimuli, however there is little research about the way that individuals with autism process stimuli in to categories. Previous studies have suggested that, in typically developing individuals, detection and categorization are simultaneous, but in autistic individuals a reduction in the interaction of cognitive processes causes detection to occur before categorization.

The proposed research is designed to study categorization in autistic and Asperger participants (compared to non-affected individual) using electroencephalograms to measure event-related brain potentials in response to brief presentations of image scenes and during object discrimination, detection, categorization and sub-categorization tasks.

The questions to be answered include: are certain discrimination and categorization tasks advanced in autistic individuals? Is object detection faster in individuals with autism? Is discrimination reduced in both new and well-learned categories in autism?

What this means for people with autism: Children with autism are reported to resist generalization during intervention training, although categorization is crucial for most cognitive processes. Understanding how autistic individuals use and access categorical information could lead to improvements in intervention and educational methods (e.g., the way new material is presented and how new concepts are taught). 

Mentor: Boutheïna Jemel, Ph.D.
Rivière des Prairies Hospital / Fernand Seguin Research Center
Post-doctoral Fellow: Isabelle Soulières, Ph.D.

Investigation of interactions between processing levels via categorization processes

Children with autism have been shown to show differences in the ability to categorize information and process novel stimuli, however there is little research about the way that individuals with autism process stimuli in to categories.

Previous studies have suggested that, in typically developing individuals, detection and categorization are simultaneous, but in autistic individuals a reduction in the interaction of cognitive processes causes detection to occur before categorization. The proposed research is designed to study categorization in autistic and Asperger participants (compared to non-affected individual) using electroencephalograms to measure event-related brain potentials in response to brief presentations of image scenes and during object discrimination, detection, categorization and sub-categorization tasks.

The questions to be answered include: are certain discrimination and categorization tasks advanced in autistic individuals? Is object detection faster in individuals with autism? Is discrimination reduced in both new and well-learned categories in autism?

What this means for people with autism: Children with autism are reported to resist generalization during intervention training, although categorization is crucial for most cognitive processes. Understanding how autistic individuals use and access categorical information could lead to improvements in intervention and educational methods (e.g., the way new material is presented and how new concepts are taught). 

Mentor: Catherine Lord, Ph.D.
University of Michigan, Ann Arbor
Pre-doctoral Fellow: Katherine Gotham

Measuring Severity in Autism Spectrum Disorders

Basic and clinical autism research relies on an accurate assessment of the severity of core autism features—currently measured largely in terms of language delay and cognitive functioning. Researchers use two primary tools to rate the severity of autism symptoms among groups of patients: the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). However, these measures are affected by verbal level, chronological age, and IQ, and are not always appropriate to compare symptom severity between children.

The ADOS has been effective in categorizing children who definitely have autism or not, but is not as accurate for making distinctions involving children with milder ASDs.To address the limitations of these diagnostic measures and to make the ADOS and ADI-R experimentally useful for addressing symptom severity, Dr. Lord, along with pre-doctoral fellow Katherine Gotham, will standardize scoring of the ADOS and ADI-R.

This will be done using a large database of more than 1,600 assessments from the clinic at the University of Michigan . Scores will be calibrated and standardized based on age and language level. This will allow them to approximate a scale of “autism severity” based on ADOS and ADI scores that is independent of developmental and language levels across the age range. This standardization will allow for a better comparison of assessments across time, improve inter-rater reliability, and offer an option for predicting outcome in children with ASD.

What this means for people with autism: This research will re-calibrate two highly-used diagnostic tools to allow accurate comparisons of the severity of autism across groups of people. It will create and ADOS “calibrated severity metric” for use by other researchers to more accurately quantify severity of symptoms and for subtyping autism into different categories so the causes may be better explained. 

Mentor: Jan van Santen, Ph.D.
Oregon Health Sciences University
Pre-doctoral Fellow: Emily Tucker

Quantitative Analysis of Expressive Prosody in Autism

Recent developments in speech technology make it possible to create far more precise and objective measures of speech and language ability. The research in this fellowship grant is part of a larger program to develop new technologies to measure and characterize prosody in people with and without autism. Prosody describes the acoustic properties of speech, including pitch, timing, amplitude and velocity, which are considered critical for communicating emotions, intent and directing attention. Research has shown that people with autism have deficits in “expressive” prosody that is speech directed at others. There has been little research on how well people with autism interpret other’s prosody—called “receptive” prosody—but an inability to process prosody could explain the difficulties people with autism have understanding social cues.

What this means for people with autism: Results from this research will not only help researchers better understand prosody impairments in people with autism, but will also lead to new and powerful measures for early diagnosis of the disorder that are both precise and objective. These measures may lead to the discovery of autism subtypes, thereby enabling better-targeted intervention.


Autistic people have fought the inclusion of ABA in therapy for us since before Autism Speaks, and other non-Autistic-led autism organizations, started lobbying legislation to get it covered by insurances and Medicaid. 

ABA is a myth originally sold to parents that it would keep their Autistic child out of an institution. Today, parents are told that with early intervention therapy their child will either be less Autistic or no longer Autistic by elementary school, and can be mainstreamed in typical education classes. ABA is very expensive to pay out of pocket. Essentially, Autism Speaks has justified the big price tag up front will offset the overall burden on resources for an Autistic’s lifetime. The recommendation for this therapy is 40 hours a week for children and toddlers.

The original study that showed the success rate of ABA to be at 50% has never been replicated. In fact, the study of ABA by United States Department of Defense was denounced as a failure. Not just once, but multiple times. Simply stated: ABA doesn’t workIn study after repeated study: ABA (conversion therapy) doesn’t work. 

What more recent studies do show: Autistics who experienced ABA therapy are at high risk to develop PTSD and other lifelong trauma-related conditions. Historically, the autism organizations promoting ABA as a cure or solution have silenced Autistic advocates’ opposition. ABA is also known as gay conversion therapy.

The ‘cure’ for Autistics not born yet is the prevention of birth. 

The ‘cure’ is a choice to terminate a pregnancy based on ‘autism risk.’ The cure is abortion. This is the same ‘cure’ society has for Down Syndrome. 

This is eugenics 2021. Instead of killing Autistics and disabled children in gas chambers or ‘mercy killings’ like in Aktion T4, it’ll happen at the doctor’s office, quietly, one Autistic baby at a time. Different approaches yes, but still eugenics and the extinction of an entire minority group of people.

Fact: You can’t cure Autistics from being Autistic.

Fact: You can’t recover an Autistic from being Autistic.

Fact: You can groom an Autistic to mask and hide their traits. Somewhat. … however, this comes at the expense of the Autistic child, promotes Autistic Burnout (this should not be confused with typical burnout, Autistic Burnout can kill Autistics), and places the Autistic child at high risk for PTSD and other lifelong trauma-related conditions.

[Note: Autism is NOT a disease, but a neurodevelopmental difference and disability.]

Fact: Vaccines Do Not Cause Autism.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: