Childhood autism is a clinical syndrome characterized by a triad of abnormalities in social interaction, verbal and nonverbal communication, and imaginative activity. The pathophysiological hypotheses that best fit the clinical and epidemiological findings are that: (a) the triad occurs when specific functional systems in the brain are damaged or develop abnormally; (b) qualitative variation in the triad results from differential involvement of the components of these systems; (c) the presence of additional deficits, not included in the triad, indicates the involvement of additional brain systems. The anatomical hypotheses that best fit the clinical findings are that the triad results from dysfunction in frontotemporal """"""""mesolimbic"""""""" cortex, orbitofrontal cortex, amygdala, hippocampus, neostriatum, or anterior and dorsomedial thalamic nuclei, all of which are part of or are connected with the limbic system. Researchers have tested primates with lesions in three of these regions - orbito-frontal cortex, amygdala, and hippocampus - and have obtained results on object and spatial discrimination reversal learning tasks, and on galvanic skin response to repeated and novel tones, which differentially reflected the site of lesion. We will use paradigms adapted from these studies, and from related studies, to test the hypotheses that: (a) autistic Ss will show deficits on these measures compared to appropriate controls; (b) subgroups of autistic Ss will have response patterns corresponding tothe orbitofrontal, amygdaloid, and hippocampal patterns. We also will examine the correlations between results on these measures and clinical abnormalities not part of the triad. Autistic and control Ss will be evaluated experimentally using (a) discrimination reversal learning tasks, (b) the Wisconsin Card Sorting Test, (c) a spatial maze task, and (d) psychiophysiological responses to repeated and novel tones. Those autistic Ss who fall within the age and intelligence norms of standard neuropsychological tests will be given a comprehensive battery of these tests. Language functioning, general intelligence, neurological status, and background developmental, behavioral, and medical information will be obtained using standard instruments and structured interviews and examinations. Ss will be designated as autistic or non-autistic on the basis of presence or absence of the triad, as determined by structured clinical evaluation and observation.
