Current neurobiological theories of autism propose that the disorder results from developmental abnormalities in neocortex, limbic system and/or cerebellum. Neuropsychological evidence of impaired executive function, and evidence of disturbed metabolism, blood flow and functional connectivity, indicate that abnormalities in neocortical systems may be primary to this condition. In order to directly examine the functional integrity of neocortical and subcortical neural systems in autism, we will conduct funcitonal magnetic resonance imaging (fMRI) studies of the reflexive and voluntary control of eye and hand movements. The brain systems controlling both types of movement are well-delineated neuroanatomically and neurophysiologically, and we have previously established edficits in both domains of functioning in autism. These systems are therefore ideal targets for clinical functional neuroimaging studies. Using high-field echo-planar fMRI and well-validated behavioral paradigms, we will undertake studies to characterize the physiology of neocortical and subcortical systems in autism with unprecedented spatial and temporal resolution. We will examine developmental aspects of executive functions by assessing relevant behavioral and neurophysiological parameters during the ages when executive functions mature to adult levels. This will be done through annual behavioral testing of pediatric autistic patients and matched controls recruited between the ages of 8 and 13, and a follow-up fMRI study of these cases conducted 4 years after initial imaging studies. The proposed investigations are designed to directly establish clinico-pathological relationships and thereby clarify the neurophysiologic basis of disturbed executive functions in autism, and to examine underlying cortical neural circuitry abnormalities within a developmental framework.

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Mellon Pitts Corporation (Mpc Corp)
United States
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