2007 Pilot Grants
2007 Pilot Grants
2007 Basic and Clinical Awards
2007 Treatment Grants
Alberto Ascherio, M.D., MPH
Harvard School of Public Health
$120,000 for two years
Maternal Risk Factors for Autism in the Nurses Health Study II – a Pilot Study
Established in 1989, the Nurses Health Study II has prospectively evaluated many aspects of women’s health in a cohort of over 100,000 women in the United States.
The information collected on this group include medical, obstetrical, and prospectively collected dietary factors, as well as neurodevelopmental diagnosis of children born to women in this cohort.
This allows for a unique opportunity to investigate a wide range of environmental factors, including maternal dietary and reproductive factors, which may be associated with risk of developing autism spectrum disorders.
Diet and medical history of mothers with a child with autism, as well as those who did not report a child diagnosed with autism, will be studied using information gathered prior to pregnancy.
These children and their parents will be screened using the social responsiveness scale (SRS) and then followed up by the Autism Diagnostic Instrument-Revised (ADI-R). Utility of the SRS, which measures autism severity using one quantifiable score, as a diagnostic instrument will also be investigated in this study.
What this means for people with autism: In addition to diet and obstetrical complications, this study will provide support to evaluate the feasibility of using this extensive and well-researched project to study risk factors associated with autism. This project provides a unique opportunity to use existing data in order to determine the role of environmental risk factors on neurodevelopment for a better understanding of the cause and possible preventative measures. (Co-sponsor: The Higgins Family Charitable Foundation)
Abha Chauhan, Ph.D.
Institute of Basic Research, Staten Island, NY
$119,974 for two years
Oxidative Stress and Immune Response in Autism
Dr. Chauhan and colleagues at the IBR will investigate biochemical changes associated with autism, particularly as they relate to markers of oxidative stress.
Oxidative stress is a process that occurs when the generation of free radicals in the cell during normal metabolic processes overwhelms the normal defense mechanisms and leads to damage or death of cells in tissues essential to normal function.
Oxidative stress has been associated with neurodegenerative diseases and may be linked to an abnormal immune response. This project will examine blood of children affected with autism and their non-affected siblings to determine various markers of oxidative stress, the inflammatory response and the function of the immune system.
In addition to diagnostic assessment, the symptom severity will be established to better understand the influence of the oxidative stress and immune responses in subgroups of children with autism spectrum disorders.
What this means for people with autism: This study will allow the investigators to measure a wide array of markers associated with oxidative stress, thereby providing a better understanding of the mechanism by which oxidative stress may occur in individuals with autism. Isolation of a particular biomarker in a subgroup of children with autism will lead to better treatments and potentially improved diagnostic assessments.
Yue Chen, Ph.D.
Harvard Medical School / Mclean Hospital
$120,000 for 2 years
Cortical Mechanisms Underlying Visual Motion Processing Impairments in Autism
Autism is typically recognized by disturbed social, communicative and imaginative functions. Sensory and cognitive processing, however, may also be altered and play an important role in the pathophysiology of this neurodevelopmental disorder. One emerging hypothesis is that autism is a neural disorder involving a widely distributed brain network, as opposed to a single, specific brain lesion.
Although it can explain the diversity of autistic features, this brain network hypothesis remains to be tested at a neural systems level. This project will study brain processing of global and local motion signals in autism. Global motion processing requires spatiotemporal integration over a network of neural components whereas local motion processing does not.
Using a psychophysical approach, Dr. Chen and colleagues will examine global and local motion perception in autism patients (n=30), and in age- and sex-matched normal controls (n=30). The investigators will measure perceptual thresholds in the detection of the directions of global and local motion. Using an fMRI approach, they will examine the pattern of cortical activations while autism patients (n=10) and controls (n=10) perform the global and the local motion tasks. The level of fMRI BOLD signal changes in both sensory (extrastriate) and cognitive (prefrontal) cortices will be measured.
This study will generate empirical data on whether and how global motion perception, a sensory process that provides critical visual signals for cognitive and social functioning, is altered in autism.
What this means for people with autism: Ultimately, research on selected sensory and cognitive processes will lead to the identification of pathophysiological factors underlying autism, upon which targeted and effective intervention can be developed.
Andrew Chiba, Ph.D.
University of California San Diego
$120,000 for 2 years
Attentional abnormalities in autism: an electrophysiological study of the basal forebrain and central nucleus of the amygdala
One prominent alteration in autistics lies in attentional processing. People with autism show specific deficits in some attentional tasks and better than normal performance in others. Attentional processing is carried out in the brain in large part by the basal forebrain cholinergic system.
This system is also modulated by the amygdala. Both the basal forebrain and the amygdala have been shown to be atypical in autistic brains, with the central nucleus of the amygdala (CN) containing unusually small, densely packed neurons, and the substantia inominata/nucleus basalis (SI/nBM) region of the basal forebrain containing exceedingly high levels of BDNF, a neurotrophic factor that is implicated in neuronal excitability.
The aim of this project is to use an animal model to determine whether these known abnormalities of autistic brains can themselves mediate the atypical attentional patterns of behavior seen in autism.
Neural recordings will be obtained in the SI/nBM and CN of rats during attentional tasks comparable to those impaired in autistics, and that have been shown to be dependent upon function of the basal forebrain cholinergic system. Neural activity and behavior will be monitored after partial lesions of the CN, and after infusion of high levels of BDNF into the SI/nBM.
What this means for people with autism: By characterizing alterations in neuronal function arising from dysfunction in this system, it may be possible to define target sites for therapeutic intervention to aid attentional processing in individuals with autism.
Debra Gusnard, M.D.
$120,000 for 2 years
Communication and Prosody in Autism: A Pilot fMRI Study Using a Sib-Pair Design
Impairments in communication and social interaction are defining characteristics of individuals with autism spectrum disorders. Even when other aspects of their language function improve, autistic people often continue to have problems with an aspect of speech known as prosody.
Prosody contributes significantly to the ‘personal’ information that is conveyed by speech and enables individuals to participate in the construction of a socially meaningful and effective conversation.
The limited data on perception of prosody in autism suggests the greatest impairment is in the domain of prosody’s emotional-pragmatic functions (when a person’s manner of speech conveys that they feel angry, for example) rather than its grammatical functions (when a person’s manner of speech expresses a question rather than a statement, for example). Emotional prosody will be the focus of the current investigation.
The investigators propose that difficulties with prosody for individuals with autism spectrum disorders may be related to underlying abnormalities in the connectivity among brain regions.
Behavioral testing and magnetic resonance imaging will be used to address this under-researched issue and its neurobiology in a systematic and detailed fashion. Brand new imaging techniques will allow the investigators to assess the autistic individuals’ brain responses to emotional speech at the same time that they assess the connectivity among important brain regions.
The researchers will also compare the data from the autistic subjects to that of some of their unaffected siblings and to unrelated control subjects. This feature of the project offers the possibility of preliminarily identifying ‘markers’ in the brain that may be different between families and could help guide future studies.
What this means for people with autism: When capacity for prosody is abnormal, this has the potential for impeding the social interaction and integration of such individuals. These brain imaging results could provide important data on mechanisms underlying fundamental difficulties in autism and help explain why some individuals may be more impaired than others.
Antonia Hamilton, Ph.D.
University of Nottingham
$59,831.21 for 1 year
Goal Understanding in the Autistic Brain
The aim of this project is to test a hypothesis of social disability in autism by examining the brain systems underlying a key social skill – goal understanding – which may be abnormal in autism.
Most people effortlessly infer goals; if you see a boy reach towards a cookie, you know he wants the cookie and his goal is to take the cookie. This ability depends on a set of brain regions called the ‘mirror neuron system’, which are critical for imitation and social interactions. Some researchers hypothesize that the mirror neuron system is broken in children with autism, causing social disabilities in imitation, language and emotions.
The present project tests the broken mirror hypothesis of autism by studying how the autistic brain processes other people’s goal-directed actions. Typical adults and adults with autism or Asperger’s syndrome will be asked to watch videos of goal-directed actions, such as a person taking a cookie, during functional magnetic resonance brain imaging.
Analysis of brain activation will demonstrate if goal processing is normal or abnormal in the autistic brain. If goal processing is normal, this means that the broken mirror hypothesis of autism is incorrect, and that therapies for autism should build on the autistic individual’s understanding of goals to teach other social skills.
In contrast, if the data show that goal processing is abnormal in autism, this will mean that behavioural interventions that target the function of the mirror neuron system would be beneficial for individuals with autism.
What this means for people with autism: The results of this study will have important implications for our theoretical understanding of the neural and cognitive causes of social disability in autism, and for the development of interventions to improve these social disabilities.
Christopher Hass, Ph.D.
University of Florida
$120,000 for 2 years
Motor Control in Young Children with Autism
This research project focuses on assessing the ability to control posture and movement in young children with autism and the relationship to restricted, repetitive and stereotyped patterns of behaviors (RRBs) in autism.
Dr. Hass and his colleagues will use standardized clinical testing and biomechanical evaluation of performance on tasks with increasing challenge of motor skills to examine motor control abilities in children with autism.
He will test the hypothesis that children with autism that display more RRBs will also show difficulties balancing and a greater degree of postural instability as compared to those who are not affected. This will include standard diagnostic and neuropsychological tests of autism together with assessments of postural control of children while they are standing, as well as moving.
What this means for people with autism: Currently, little is known about the best way for a therapist to approach a young child with autism. Results from the proposed study will provide direct insight into postural control in children with ASD so that evidence-based and targeted physical and occupational therapy can be developed in better ways.
Exploring Functional Brain Connectivity for Visual Cognition in Autism Spectrum Disorder
An essential characteristic of Autism Spectrum Disorder (ASD) is impaired social behavior, such as difficulties in processing emotional and non-verbal social signals in faces. This deficit in face processing may be caused by abnormal social communication or it may reflect a more basic problem in face perception and recognition.
Recent reports suggest that children with ASD are more likely to emphasize individual features of faces (e.g. eyes, nose, mouth) more than the overall configuration of the face. Individuals with ASD also exhibit different brain activation patterns than do non-ASD individuals for face processing and other cognitive tasks.
Recent preliminary data from Dr. Joseph’s laboratory suggest that normally developing (ND) children have fewer connections among brain regions for face processing compared to adults. Consequently, this “underconnectivity” pattern may reflect an immature, but normally developing brain network, or a reflection of atypical development.
The goal of this study is to compare functional brain connectivity patterns for face and object processing in children with ASD and ND children using functional magnetic resonance imaging (fMRI) technology.
This study will explore whether underconnectivity patterns reflect a general property of the functional brain organization of ASD, or whether connectivity patterns depend on the specific type of processing (e.g., face vs. object recognition; or local vs configural processing). In addition, this study will characterize functional brain organization for face processing in typical development.
What this means for people with autism: The need to understand the normal developmental course of face processing is essential in guiding the interpretation of brain organization for face processing and our attempts to improve it and overall social recognition in ASD.
Raymond Kelleher, M.D., Ph.D.
Massachusetts General Hospital
$120,000 for 2 years
An Adult Brain-Specific Mouse Model of Neuronal TSC Inactivation
Whilst the genetic basis of autism is complex, several childhood disorders characterized by mental retardation are due to mutations in single genes and are associated with a high incidence of autistic features.
Understanding the impact of mutations of such genes on brain development and function promises to provide important insights into the causes of autism, and may help identify potential therapeutic strategies. Tuberous sclerosis complex (TSC) and fragile X syndrome (FXS) are known risk factors for autism and recently, the gene products that are mutated in TSC and FXS have been shown to be involved in the regulation of protein synthesis which is important for memory formation.
Thus it is possible that aberrant regulation of protein synthesis in brain cells may contribute to the development of autism. In an experimental mouse model, in which the TSC gene has been genetically modified over the entire life span (including embryonic development), abnormalities in brain development are seen which are similar to those people with TSC. This approach does not distinguish the critical period (i.e. pre- or post-natally) in which the abnormal TSC gene exerts its effect.
The present study will use a TSC mouse model to examine the relationship between brain abnormalities and behavioral and cognitive impairments and will specifically address what happens when the abnormality in the TSC gene is induced only in the post-natal period (i.e. after birth and thereby bypassing any effects on brain development).
What this means for people with autism: This study has the capability to provide insight into gene defects, and consequently defects in protein synthesis, which occur specifically at postnatal stages. This approach will provide inroads toward a therapeutic strategy in TSC with broader implications for therapies in autism.
Young Shin Kim, M.D., Ph.D., MPH
$114,545 for two years
Prospective Examination of 6-year Cumulative Incidence of ASDs: A Total Population Study
The prevalence of autism has increased dramatically over the past 10 years, however, reported measures of prevalence do not accurately assess the role of the environment over better diagnostic techniques and service availability.
This is better evaluated by measuring the incidence of autism over time – that is, the number of new cases initially not diagnosed with autism, then later diagnosed with autism on a yearly basis using rigorous screening, standard diagnostic assessments and valid case ascertainment in a specific age category over successive years. In addition, the study must include a defined group and accurately assess all members of that group.
Because Korea is a relatively genetic homogeneous group as compared with other countries, and because the investigators have established the parameters listed above in their previous studies investigating autism in a geographically defined region in a large group of people, this is an ideal situation to examine the changes in incidence and prevalance over time.
The investigators in Korea and in the US have already developed methods to identify, screen and diagnose children with autism using a grant from Autism Speaks in 2005. Therefore, this project will allow Dr. Kim and her colleagues to analyze incidence rates over time in 6 year olds with autism in Korea.
What this means for people with autism: Both the ongoing and proposed research is potentially modeled for state-of-the-art epidemiological research on ASDs across cultures.
Along with the ongoing prevalence study, the proposed study will provide incidence proportions of ASD up to age 6 among four consecutive birth cohorts. This pilot study, along with futuresurveillance studies, will pave the way to answering critical questions about the cause of the increase in autism over the past decade.
Michael Murias, Ph.D.
University of Washington Autism Center
$120,000.00 for 2 years
Electrical Measures of Functional Cortical Connectivity in Autism
Current models of autism spectrum disorder suggest alterations in integrated brain functioning at both cognitive and anatomical levels. Large-scale brain abnormalities in autism include increased brain volumes in young affected individuals that appear to be mainly caused by increases in white matter (which forms the connections between different brain regions). This suggests that altered connectivity among brain networks, rather than changes in function in any single cortical region, may form the anatomical basis of the cognitive impairments in social, language and communication functions found in ASD.
This proposal employs electroencephalographic (EEG) coherence methods to investigate functional connectivity in autism spectrum disorder. EEG coherence quantifies the degree of synchronization between different parts of the brain, and is believed to reflect the functional connections between brain regions. Prior work applying EEG coherence methods to adults with autism in the resting state has demonstrated, for example, robust patterns of decreased connectivity, primarily in long distance connections involving the frontal lobes. This proposal expands on prior work demonstrating resting state differences, and it investigates functional connectivity in a visual perception task. Further understanding of the dynamic functional processes that occur in resting and controlled cognitive states will inform understanding of altered cortical physiology in ASD.
What this means for people with autism: Information regarding specific patterns of impairments in functional connections between brain regions may lead to knowledge and methodologies that have the potential to advance understanding of the causes, diagnosis and treatment of autism. (Co-sponsor: The Higgins Family Charitable Foundation)
Social Cognition and Interaction Training for Adolescents with High Functioning Autism
Understanding how to interact with others is a challenge for people with autism.
Impaired social cognition (i.e. perceiving the emotions and intentions of others) makes it difficult to establish friendships and form positive social relationships, and is particularly incapacitating for adolescents with autism who must navigate the world unaided by parents.
Advances in our understanding of the social cognitive impairments in autism, provides a grounding for the development of interventions to target this central deficit of autism. The goal of this study is to investigate a group-based cognitive behavioral intervention to improve social-cognitive functioning in adolescents with high-functioning autism (HFA).
The study sets out to modify a previously validated form of group-based intervention, Social Cognition and Interaction Training (SCIT), and to optimize its use for adolescents with high functioning autism (HFA).
The first step will be to develop a treatment manual to implement this training program, followed by a small, randomized controlled trial to compare the SCIT-A programme with ‘treatment as usual’. Participants will be assessed at baseline, post-treatment (18 weeks later), and at 3-month follow-up and a variety of outcomes and measures, including social cognition, social functioning, and adaptive skills will be assessed.
What this means for people with autism: The innovative treatment program will target the specific social cognitive impairments that cause difficulties with social cognition and interactions and is anticipated to help the individuals who take part in this study. The development of a manual is intended to allow for the treatment program to be standardized and, if the current small clinical trial is favorable, for the program to be transferred to a larger study group.
Lawrence Reiter, Ph.D.
University of Texas Health Science Center
$120,000 for 2 years
Identification of UBE3A substrates using proteomic profiling in Drosophila
The Reiter laboratory utilizes the genetic tools available in Drosophila melanogaster (fruit flies) to study genes related to autism, specifically the protein targets of the ubiquitin ligase E6-AP (gene name UBE3A). Mutations in the UBE3A gene cause a mental retardation disorder known as Angelman syndrome. Recently it has been shown that duplication of the genomic region containing this gene could be the underlying cause in as many as 3% of all cases of inherited autism.
This project will use the genetic power of fruit flies to identify genes regulated at the protein level by E6-AP. Several techniques will be used to generate artificially high levels fly Dube3a protein in fly heads. The investigators will then use protein sequencing (proteomics) to identify those proteins affected by changes in the levels of Dube3a protein.
Upon validation, proteins that appear to change their expression in this analysis will be considered as new autism genes. In a separate collaboration, these potential autism genes will then be analyzed as susceptibility factors in families where autism appears to be inherited.
What this means for individuals affected by autism: This novel approach will allow identification of genes that may prove useful as therapeutic targets for the treatment of disorders ranging from Angelman syndrome to autism.
Nilanjan Sarkar, Ph.D.
$120,000 for 2 years
Innovative Technology for Mapping Social Engagement in Children with Autism: Adaptive Physiological Profiling in Real Time
Social communication and social information are thought to represent core domains of impairment in children with Autism Spectrum Disorders (ASD). The impact on the individual, the family and society associated with these vulnerabilities is enormous. A better understanding of the biological and physiological mechanisms underlying these symptoms is needed, together with the creation of research tools that can be used to create optimal intervention strategies.
This study is designed to promote the development and validation of an innovative technological approach for understanding the physiological aspects of social communication in children with ASD and developing an intervention tool. The research program brings together a multidisciplinary team of researchers with expertise in clinical research, engineering and computer science.
The primary aim is to use cutting-edge knowledge to develop a system to augment human-computer interactions in interventions with children with ASD. It will do this by making a Virtual Reality system capable of recognizing and responding to behavioral cues of the child based on his/her physiological responses. The type of physiological signals that will be measured include heart rate, skin responses (linked to sweat gland activity), muscle tension and body temperature.
These responses are in fact signals about emotional states such as anxiety, task liking and task involvement. Measuring these physiological signals will enable the selection and adaptation of Virtual Reality social interaction scenarios and define the environment that the child with ASD feels most comfortable interacting with.
What this means for people with autism: Research suggests that people’s interactions with computers are typically social and natural and parallel natural settings.
A Virtual Reality system, in which environments can be controlled or changed, can allow role play in a setting designed to mimic the real world. This holds potential for children with ASD and may be used to facilitate social and behavioral interventions.
Andre Sourander, M.D.
Turku University, Turku, Finland
$119,075 for two years
Early Developmental Risk Factors for Autism in a National Birth Cohort
This pilot study will establish a new project called the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FiPS-A). The FiPS-A is based on the Finnish Maternity Cohort (FMC), which consists of virtually all births in Finland (N=1.1 million) from 1987- 2005. The investigators will use maternal medical and exposure history collected during pregnancy to examine if infection, hormonal abnormalities and smoking are related to an increased risk of autism in their children in a subset of these 1.1 million births.
This study will also be able to identify potential early risk factors including improper growth and development before the child was diagnosed to assess whether these parameters can be included in early signs of autism. In addition to medical data, this project has the ability to analyze blood samples that were drawn during pregnancy in a random sample of children who are diagnosed with autism, and a random sample of children without autism, all of whom were in the national FMC cohort.
What this means for people with autism: This project has the potential to become one of the largest epidemiological studies to investigate prenatal and perinatal risk factors in autism, including a large biomarker repository to isolate possible early prenatal risk factors.
In addition to studying the longitudinal development of children who later develop autism, multiple environmental factors, including medical information from the mother and child, will be studied for further analysis.
John Vincent, Ph.D.
University of Toronto, Canada
$109,394 for 2 years
Identification of Autism Candidate Genes on the X-Chromosome from Copy Number Variants Identified by 500K SNP-Chip Analysis
The pronounced 4 to 1 boys to girls ratio reported in autism had long led scientists to speculate that the X chromosome, present in two copies in girls and only one in boys, may hold clues to the genetic component of the disorder.
Using the latest ”gene chip” technology, Dr. Vincent and his colleagues have recently identified 15 novel copy number variants (CNV), or submicroscopic DNA insertions and deletions, on the X chromosome of some individuals with autism that appear absent in control samples. Building on this preliminary finding, Dr. Vincent plans to examine these CNVs in a larger collection of affected and a variety of control samples in order to validate them as specific to autism, and if so, whether they are de novo or inherited in origin.
What this means for people with autism: Since some of these CNVs span genes known to be involved in mental retardation, neuronal development, and synaptic plasticity and signaling, this study may help identify new autism susceptibility candidate genes quickly. Such discovery may inform us about the disease mechanism and allow subtyping of the population that has important implications for diagnosis as well as treatment.
Larry Young, Ph.D.
$120,000 for two years
Genomic Resources for Identifying Genes Regulating Social Behavior
Understanding the genetic and neurobiological mechanisms underlying social behavior will provide insights into determining how these systems go wrong in individuals with developmental disorders including autism.
Using a naturalistic animal model, this study will examine the genetic influences on social behavior using two different species of rodents called voles. One species, the prairie vole, forms strong social bonds, while the other, meadow voles, does not.
Previous research has suggested that the difference in this social behavior may be due to a “microsatellite” region of genetic material that is located outside the area which transcribes the gene for the peptide hormone receptor avpr1.
The molecules on which this receptor works, called oxytocin and vasopressin, have been shown to regulate this social affiliative behavior. Therefore, these researchers will create markers for these microsatellites as well as establish different strains of voles which show differing levels of social behaviors.
What this means for people with autism: This set of molecular markers, used in conjunction with selectively bred lines of voles that differ in their ability to form social bonds, will allow for the discovery of genes that contribute to variations in social behavior. This strategy may ultimately lead to novel pharmacological interventions to selectively treat the social deficits associated with ASD.
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 work. In 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.