Infantile autism is a neurobiological disorder in which the development of many higher cognitive, affective, and communicative functions are severely disrupted, resulting in language, social, and integrative deficits. Until recently, the concept that neuroanatomical abnormalities may underlie the neurofunctional deficits in autism has not been systematically investigated. The advent of a powerful, yet non-invasive in vivo imaging method -- magnetic resonance (MR) imaging -- combined with disciplined quantitative measurement algorithms, has made it possible to obtain accurate and meaningful neuroanatomic data from living patients. Comparison of neuroanatomical data obtained in this manner with data from neurofunctional studies in the same patients with autism has yielded important new insights into the disorder. The investigator has disclosed through MR imaging research that specific sites of anatomical abnormalities are present in the parietal lobe and in the cerebellum in diagnostically confirmed autistic patients as young as 5 years of age. Quantitative analysis of MR imaging and neurofunctional data indicate that the size of these specific sites of abnormality is related to the degree of deficit in specific attention operations. For example, the amount of volume loss in superior parietal cortex is highly correlated with the degree of behavioral impairment in detecting stimuli located outside a principal focus of visual attention; such stimuli also elicit abnormally reduced visual neurophysiological responses in autistic patients with the greatest amount of parietal volume loss. Their other studies have found that autistic patients with the most vermian abnormality orient attention more slowly than those who have less vermian abnormality. Parallel studies of patients with autism and patients with acquired focal cerebellar lesions have shown that both patient groups are abnormally slow to shift attention between visual and auditory information, and have abnormally reduced brain responses to cues signalling attention shifts. These findings show great promise in elucidating the relationship between brain site and function in autism and in the normal brain, but require confirmation in the carefully designed brain-behavior studies outlined in this proposal. To explore the relationship between sites of anatomical abnormality and deficits in specific attention operations in autism, the investigator proposes to acquire in autistic and normal subjects behavioral and neurophysiological measures of three specific operations -- orienting, shifting, and distributing attention -- a statistically correlate these measures with the size of various cerebral, cerebellar, and subcortical structures. They also propose to acquire functional MR imaging measures in order to more directly identify anatomical structures whose deficits underlie impairment in shifting attention in autism. The completion of this study will further their long-term objective of elucidating the anatomical substrate of neurofunctional deficits in autism.
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