Autism is a fascinating disorder of complex cognitive abilities and behavior which may ultimately prove to be the consequence of an abnormality in neural connectivity at the systems level. Neurobiologic research in the past 10 years has substantially redefined the neurobiologic characterization of autism, with the predominance of evidence now pointing to dysfunction of cerebral cortex. Based on our research findings to date, our worKing hypotheses propose that the selective pattern of cognitive deficits in autism is secondary to a generalized deficit in complex information processing and is characterized by a dissociation between complex tasks and more basic abilities across domains and modalities. We further hypothesize that these deficits are the consequence of a generalized abnormality in the development of the local and distant connections of association cortex. The goal of this proposal is to investigate the structural and functional evidence for the role of the cerebral cortex in the pathophysiology of autism. This goal will be accomplished through the study of 100 carefully diagnosed and screened high functioning autistic individuals aged 8-30 years and 100 normal controls individually matched on age, IQ, gender, and race and group matched on SES of the family of origin. These subjects will have: 1) a battery of neuropsychologic and language tests designed to demonstrate the distinctive pattern of cognitive deficits and abilities in autism; 2) studies of cortically controlled eye movements to investigate the physiology and circuitry of the cerebral cortex; 3) quantitative morphometries of the brain with volumetric MR imaging to provide measurements of unimodal and heteromodal association cortex, white matter, and corpus callosum, as well as limbic and posterior fossa structures relevant to pertinent negative hypotheses; and 4) 31P and `H MRS to investigate the molecular metabolic neuropathology autism by assessing the phospholipid metabolism of brain membranes and neuronal cell number respectively, and thus providing a potential independent measure of the underlying pathophysiology in autism. The data from these studies will be used in various binations in correlational analyses to test the hypotheses of this study. These analyses will include pertinent positive tests of our hypotheses as well as tests of pertinent negative tests.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS033355-04S1
Application #
6071575
Study Section
Neurology A Study Section (NEUA)
Program Officer
Hirtz, Deborah G
Project Start
1995-05-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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