Cerebellar abnormality may underlie many of the cognitive and clinical symptoms in autism. While brain abnormalities in autism are diverse and involve cortical and subcortical regions, the cerebellum is the most consistently reported site of damage. Developmental abnormality of the cerebellum has been found in 95% of postmortem autism cases and in several hundred individuals with autism on quantitative MRI studies performed by six independent research groups. More than 60 studies have found molecular, metabolic, functional or structural abnormalities of the cerebellum in autism. A rapidly growing body of literature suggests that the cerebellum controls or modifies diverse cognitive processes, thus altering the traditional neurologic view of the cerebellum as a brain structure that supports only motor function. Work in our laboratory has linked the cerebellum to both cognitive function and neural response not only in autism, but also in normal function. We have proposed that some deficits in autism may reflect fundamental cerebellar dysfunction--failure to track sensory information, predict future events and prepare a response. We now propose to test this emerging model of cerebellar dysfunction in autism using functional and structural imaging. We will assess the specificity of cerebellar involvement in these cognitive operations (track, predict, prepare) by comparison of subjects with autism: 1) to patients with cerebellar damage acquired in early childhood; and 2) to those with Asperger syndrome in which the cerebellum may be less affected. We will ground our results from these comparisons by performing fMRI (functional magnetic resonance imaging) studies in normal control subjects to establish that the cerebellum is normally active during these same operations. The fMRI studies of clinical groups will allow us to investigate whether patterns of activation suggest abnormal interaction of the cerebellum and cerebral cortical systems during these important processing operations. Our studies will link both behavioral and neural response (ERP, fMRI) to the underlying neuroanatomy (MRI). These results will help us understand the specific functional deficits associated with developmental or acquired damage to the cerebellum and thereby will contribute to understanding the brain substrates of behavioral dysfunction in autism. Such knowledge may enable more effective treatment and aid the search for the origins of this debilitating disorder.
