Autism Spectrum Disorders (ASD) are characterized by specific impairments in the domains of social and communicative skills as well as the presence of restricted, repetitive, and stereotyped behaviors, interests and activities. In addition, approximately 10% of individuals with ASD show """"""""savant skills"""""""" performing significantly above normal on tasks such as memory and mathematics. ASD is currently considered one of the most prevalent childhood disorders affecting over 1.5 million children in the US alone. Despite its prevalence and detailed behavioral characterization, the underlying neural mechanisms mediating these behaviors have remained a mystery, though many theories exist. The identification of a neural basis for ASD will allow for novel, more effective treatments targeting the underlying cause of the behavioral symptoms rather than simply treating the behaviors. Recent findings in neuroscience suggest that individuals with ASD have significantly more intracortical white matter (connections) in their cortex, especially in frontal regions. The current proposal seeks to extend this finding and investigate whether the reported overconnectivity may lead to enhanced plasticity in these individuals which may account for some of the positive symptoms, including echolalia, echopraxia, and savant skills seen ASD. Non-invasive transcranial magnetic stimulation (TMS) provides an excellent technique of evaluating plasticity of the cerebral cortex. During the paradigms proposed here, we will apply TMS to the motor cortex and evaluate the resulting motor evoked potential (MEP) both prior to and following experimental manipulations. The tasks that were chosen for this proposal have been shown to provide information regarding LTP and LTD formation in typical individuals. Additionally, as these tasks do not require the participant to concurrently perform a cognitive task, it is free of confounds such as differences in motivation, perceived task difficulty, or behavioral strategy that many fMRI studies cannot control for.
The aim of the proposed studies is to investigate whether the reported overconnectivity leads to enhanced plasticity in individuals with ASD. Enhanced plasticity of cortical connections may provide a neural mechanism underlying the behavioral symptoms which characterize ASD. Additionally, in conjunction with other studies, it is our hope that the information gained by this study may lead to the development of novel therapeutic strategies to treat the underlying cause of the disorder rather than the behavioral symptoms. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH080493-02
Application #
7497590
Study Section
Special Emphasis Panel (ZRG1-F12A-D (20))
Program Officer
Churchill, James D
Project Start
2007-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$46,826
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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Oberman, Lindsay M; Horvath, Jared C; Pascual-Leone, Alvaro (2010) TMS: using the theta-burst protocol to explore mechanism of plasticity in individuals with Fragile X syndrome and autism. J Vis Exp :

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