Infantile autism is a neurological disorder that severely disrupts social, cognitive, and language development. The neurophysiological/neuroanatomical defects responsible for autism have, until recently, resisted discovery. The advent of a powerful, yet non- invasive in vivo imaging method -- magnetic resonance (MR) - combined with disciplined quantitative data analysis has yielded important new insight into the disorder. Our prior NIH-funded MR research has disclosed that specific sites of cerebral and cerebellar anatomical abnormality are present in diagnostically confirmed autistic patients as young as 5 years of age. Quantitative analysis of our MR imaging data indicate that specific loci of abnormality undergo distinct age-related changes in these affected patients. For example, initially small posterior callosal subregions undergo age-related growth to near normal size, yet cerebellar vermian lobules VI and VII are reduced in size in autistic subjects at all ages, and show no growth over time. Results in even younger patients with a provisional diagnosis of autism indicate that a rapid decrease in size of posterior callosal subregions and cerebellar vermian lobules may occur between the ages of 2 and 6 years. These findings are intriguing, but require confirmation in the larger, carefully designed study herein proposed. To most efficiently explore the incidence and age-related size changes in specific sites of CNS abnormality in autism, we propose a cross- sequential experimental paradigm which will obtain MR imaging data in both autistic and normal control subjects longitudinally over 5 years. Analysis of the prospective longitudinal data acquired will reveal the developmental time course of anatomical deviations in autistic patients, particularly during the age range of 2 to 6 years, an important period of rapid growth in the normal brain. The completion of this study will further our long-term objective of elucidating the neuroanatomical substrate of infantile autism.
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