This application sets forth work to extend our program of research into cerebellar substrates of cognitive and motor deficits associated with chronic alcoholism. Our recent quantitative MRI studies have confirmed our speculations that significant cerebellar tissue volume deficits are present in nonamnesic alcoholics and that these deficits extend to the superior vermian lobules and lateral cerebellar hemispheres. Further, these volume deficits have functional consequences because the severity of ataxia correlates with the extent of vermian shrinkage. These observations may have clinical significance and serve to identify risk factors for falling in alcoholics, even in those who remain abstinent. Given the complexity of standing balance, we now propose to decompose the component processes of postural stability to identify loci of impairment and to determine if the ability to make use of haptic sensory cues used to maintain balance is impaired in chronic alcoholics. In addition, we have observed significant alcohol-related deficits in nonverbal working and contextual memory. These memory tasks are also known to activate prefrontal cortex and selective regions of the lateral cerebellar hemispheres in functional imaging paradigms in healthy nonalcoholic controls. These brain regions and cognitive functions are disrupted in chronic alcoholics but a causal relationship has yet to be demonstrated. The contribution of a compromised fronto-cerebellar circuit to the cognitive deficits of chronic alcoholism will be directly assessed with functional Magnetic Resonance Imaging (fMRI). The work to date suggests separate but complementary paths to explore the importance of cerebellar dysmorphology and its contribution to functional impairment in alcoholism. The proposed work draws upon neuropsychological testing, physiological analysis of postural stability, and brain imaging with structural and functional MRI. Accordingly, we propose to 1) identify the component processes of the balance disturbances manifested by alcoholics with force platform analyses under challenge conditions, 2) explore brain functions subserved by neuroanatomical loci deficient in volume in alcoholics with fMRI paradigms that specifically activate these regions in normals, and 3) quantify the effects of chronic alcoholism on the volumes of the principal fronto-cerebellar circuitry nodes with quantitative MRI.
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