Boston University , Boston , MA
2004-2006

Principal Investigators: Helen Tager-Flusberg, Ph.D., Dae-Shik Kim, Ph.D.

Functional and Connectivity Neuroimaging of Autism.

The goal of this project is to develop over a three year period new methods that will allow exploration of brain regions that are critical for processing sounds and language. This project will utilize novel brain imaging technologies, including magnetic resonance imaging (MRI), to map out areas of the brain in control subjects that process sounds and language. This will allow us to locate brain areas in which certain processes take place and to determine how these areas are connected to one another. The project will use these technologies and knowledge on adolescents with autism to shed light on regions of the brain which may not be processing sounds or language efficiently and where connections between critical brain regions may break down in autism.

Helen Tager-Flusberg

Dae-Shik Kim

Boston University School of Medicine, Boston , MA
2004

Principal Investigator: Robert Joseph, Ph.D.

Neurobiological Markers of Language and Functioning in Autism (funded through NAAR)

This project will investigate the relationship of language acquisition to developments in connectivity between language regions of the brain, as measured by diffusion tensor magnetic resonance imaging in children with autism. Many children with autism fail to develop language or are impaired in their language functioning. Research has shown that language impairment appears to represent the influence of genes that increase susceptibility to autism. An understanding of neurobiological bases of the language deficits in autism will contribute to an understanding of autism's genetic underpinnings and neurodevelopmental etiology. Evidence of white matter brain abnormalities, particularly of cerebral white matter overgrowth, has emerged from magnetic resonance imaging (MRI) studies of children with autism. These findings have been limited to macrostructural estimates of differences in white matter volume in autism. Dr. Joseph will use diffusion tensor imaging (DTI) technology to (a) examine the microstructural integrity and coherence of white matter tracts connecting language-related regions of the cerebral cortex and (b) to evaluate relationship of white matter connectivity to actual language functioning. Dr. Joseph will collect anatomical and diffusion tensor brain images from children with autism at age 3 and one year later, and examine the relationship between white matter connectivity in language regions of the brain to measures of children's language development taken at each time. Dr. Joseph will assess whether microstructural changes in language-related white matter predict acquisition and development of language skills in children with autism.

Boston University School of Medicine

Robert Joseph

Georgetown University, Center for the Study of Learning Washington , D.C.
2001

Principal Investigator: Thomas Zeffiro, Ph.D.

Ongoing Development of a Multi-channel Diffuse Optical Tomography System for Evaluation of Language and Communication Disorders

Center for the Study of Learning

Thomas Zeffiro

Harvard Medical School, Beth Israel Deaconess Medical Center, Boston , MA
2002

Principal Investigator: Hugo Theoret, Ph.D.

Motor Output & Mirror Cell Systems in Autism Studied by Transcranial Magnetic Stimulation (funded through NAAR)

Many individuals with autism demonstrate difficulty performing simple motor imitation. This project will use a method called transcranial magnetic stimulation (TMS) to study the motor cortex and mirror cell system in adults with Asperger's syndrome. Dr. Theoret will assess the integrity of the motor cortex and mirror neuron system to gain insight into the basic cortical dysfunction that may lead to autism spectrum disorders. Dr. Theoret will use this information to investigate how these abnormalities interact with emotional processing and self-awareness, two areas of human cognition believed to be impaired in autism. The insights derived from the proposed experiments have the potential to increase our understanding of the causes of autism and lead to new therapeutic interventions.

Harvard Medical School

Hugo Theoret

Kennedy Krieger Institute/ Johns Hopkins School of Medicine, Baltimore , M.D.
2004

Principal Investigator: Stewart Mostofsky, Ph.D.

Dependent Motor Learning in Autism Examination of Visual and Somatosensory (funded through NAAR)

Increased insight into the brain mechanisms underlying autism can be gained from consideration of motor abnormalities of individuals with autism. By using tests of motor function for which the neurologic basis is well mapped out, it is possible to gain an understanding of the neural circuits impaired in autism. Motor signs can serve as markers for deficits in parallel brain systems important for control of social and communication skill impairments observed in autism. Among the most consistently observed motor abnormalities in autism is difficulty with imitation and performance of skilled motor tasks and gestures. These deficits could be secondary to a fundamental problem with acquiring motor skills. Deficiencies in motor skill learning could also result in development of a limited repertoire of movements and might explain observations of motor stereotypies. The goals of this project are to determine common factors underlying motor deficits in autism and to investigate brain abnormalities associated with these deficits using functional magnetic resonance imaging. A long-term goal is to examine the association of impaired motor skill learning with socialization and communication deficits that characterize autism. This study will provide insight into the neurologic basis of motor deficits in autism and may provide a basis for understanding the neurologic underpinnings of impaired social/communicative development.

Kennedy Krieger Institute

Stewart Mostofsky

Massachusetts General Hospital , Boston , MA
2002

Principal Investigator: Martha R. Herbert, M.D., Ph.D.

Neuroimaging of Young Children at High Risk for Autism (funded through NAAR)

In this project, Dr. Herbert will obtain MRI scans of siblings of individuals with autism at about the time of their 14-month old evaluations. These MRI scans have the potential to provide unique and crucial data related to the earliest signs of abnormal development in children who may later receive a diagnosis of autism spectrum disorder. Although many of the brain abnormalities present in autism are believed to occur prior to birth, there appear to be some abnormalities that occur after birth. Research has shown that head and brain size in individuals with autism are normal at birth but grow faster than normal during the first years of life. It has been suggested that this early increase is due to an increased amount of white matter. Dr. Herbert will analyze the MRI scans to learn about the size of various brain structures and to obtain information about the tissue characteristics in different parts of the brain. This research may provide a greater understanding about such abnormal brain growth and may lead to treatments designed to normalize the process.

Department of Neurology - Massachusetts General Hospital

Martha Herbert

Neurofeedback Group, Inc., Newton , MA
2003-2004

Principal Investigator: Barbara Scolnick, M.D.

EEG Biofeedback as an Operant Training Technique to Ameliorate Some Symptoms in Children with Autism Spectrum Disorders

The goal of this project is to test whether biofeedback of electro -encephalographic (EEG) measurements can improve the ability of children with autism, ages 8 to 16 years, to control their behavior. The experiment involves a subject group of 20 individuals who are exposed to their continuous EEG profiles while engaged in playing computer games. Each subject and aged matched controls will participate in 40 one-hour sessions over a 20 week period. The hope is to investigate whether EEG biofeedback can be a useful operant training technique to ameliorate some symptoms in children with autism spectrum disorders.

University of California at San Francisco , San Francisco , CA
2001

Principal Investigator: Timothy P.L. Roberts, Ph.D.

Neural Correlates of Phonological Processing in Autism: A MEG Investigation. (funded through NAAR)

Individuals with autism may have abnormal development of expressive speech and impairments in auditory and speech perceptual processing. Little is known about cortical mechanisms underlying impaired language development in autism. This study uses magnetoencephalography (MEG) to non-invasively measure neural activity in auditory cortical sites in individuals with autism. This technique allows researchers to track neuronal activity with sub-millisecond temporal resolution. Previous work has provided evidence that early sensory processing of simple and complex sounds appears to be intact in individuals with autism. However, the pervasive nature of language deficits in autism indicates that linguistically relevant sound processing may nonetheless be impaired in this population. The researchers hypothesize that while early processing of acoustic signal appears normal in individuals with autism, later phonological processes that provide feature extraction, discrimination, and categorization necessary for decoding the speech signal may be disrupted. They will measure later stages of neural activity, including correlates of phonological processing with the aim of providing quantitative measures to assess the nature and cortical timing of language related sound processing abnormalities in autism.

University of Pittsburgh, Pittsburgh, PA
2005-2006

Principal Investigators: Nancy Minshew, M.D., Thomas Conturo, M.D., Ph.D.

Diffusion Tensor Tracking of Connectivity Abnormalities in Autism

Recent functional imaging studies (fMRI) have revealed a reduction in functional connectivity across cortical brain regions involved in language, problem solving, and social cognition; simple tasks showed normal connectivity. Structural brain studies have shown an increase in brain volume attributable largely to an increase in the outer white matter zone. This white matter connects immediately adjacent areas of cortex and makes longer distant connections between cortical regions within the same hemisphere. The corpus callosum, the major white matter pathway connecting the two hemispheres, is smaller in autism. This study will investigate white matter connections using a new method called diffusion tensor fiber tracking to map white matter pathways related to each of the major symptom areas of autism. The size, shape and density of these pathways in high functioning teens and adults with autism will be compared to matched normal controls and behavioral indices. This study will advance the understanding of connectivity in autism, pave the way for comparisons with functional connectivity, guide developmental neurobiologic studies, and provide an index for future cognitive rehabilitation strategies designed to enhance connectivity.

University of Toronto , Toronto , Ontario
2003

Principal Investigator: Timothy Roberts, Ph.D.

MEG Correlates of Linguistic Processing at and Below the Word Level in Autism (funded through NAAR)

Magnetoencephalography (MEG) results from past studies have shown delays in automatic neural responses to vowel-sound contrasts in subjects with autism relative to controls. This study focuses on the development of a novel MEG experiment (which allows for non-invasive measurement of neural activity in auditory cortical sites) to extend investigation of auditory linguistic processing of speech sounds from isolated sounds to speech sound combinations. The combination of speech sounds is governed by phonotactic rules, language particular constraints on how sequences of segments pattern. This project will investigate sensitivity to violations of phonotactic rules of children with autism compared to controls. Literature shows that phonotactic violations cause processing delays for subjects' task completion in an auditory discrimination experiment. It is important to identify neural correlates of such delays in controls so that we may look for the presence of the same effect in children with autism in an MEG experiment. It is hypothesized that neural activity related to phonotactic violation detection will be significantly delayed in subjects with autism. The researchers will adapt existing MEG word recognition experiments to passive paradigms suitable for study with an autistic population to test whether individuals with autism store and access words similarly to healthy age-matched controls.