Face recognition skills are an important substrate of effective social skills. Persons with an autism spectrum disorder (ASD: autism, asperger syndrome and pervasive developmental disorder not otherwise specified) have a variety of deficits in the manner in which they recognize faces, including a reliance on individual facial features (particularly the mouth and not eyes) rather than the typical pattern of processing faces holistically. Functional magnetic resonance imaging studies (fMRI) of face perception in ASD have shown that two brain structures - the left amygdala and the lateral aspect of the right fusiform gyrus are functionally abnormal. These findings are especially significant because they are the first brain areas to be independently confirmed by multiple labs as involved in the pathobiology of ASDs. The role of these two structures in pathobiology of ASDs is further substantiated by postmortem brain studies and gross neuroanatomical studies using conventional structural MRI. However, there remain many important questions to be answered about the parameters that modulate activity in these brain regions, both in typically developing persons and in persons with an ASD. The experiments in this R01 application are designed to extend our current knowledge in this area through a systematic series of fMRI studies. These studies make use of infra red eye tracking technology to study the relationship between scan paths and regional brain activity. These studies involve systematic manipulation of parameters that are believed to modulate level of activity in these 2 brain areas and the functional connectivity between them. In total, we propose a link series of 4 fMRI studies, each involving a comparison between 18 persons with an ASD and 18 typically developing controls (TDCs). We hypothesis that the hypoactivation of the fusiform and amygdala in ASD is mediated by (1) variation in attention and focus of perception; (2) aspects of the stimulus parameters (e.g., degree of facial emotion); and (3) interactions between the fusiform and amygdala as information comes through cortical and subcortical visual pathways.
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