Disorders of balance and visuospatial ability are observed in alcoholics, even when abstinent. Such deficits put alcoholics, especially older ones, at excessively great risk for falling and for other accidents arising from incoordination between the visual and motor systems and from poor adaptation to change in sensory and motor input. Studies of non-alcoholic patients with cerebellar disease have shown circumscribed regions of the cerebellum to participate in selective functions of visually-guided coordinated movement, balance and motor skill learning, and of cognitive functions of timing, work production, and problem solving. Although postmortem studies consistently report tissue loss in both cerebral and cerebellar regions, in vivo neuroimaging studies have focused primarily on structural and functional abnormalities of the brain exclusive of the cerebellum. Pilot data, which suggest significant dysmorphology of cerebellar lateral hemispheres and vermis in older nonamnesic alcoholics to be related to extent of ataxia when balance is visually-guided, motivate this revised application. The purpose of the studies described in this revision remains the same as in the original application. Specifically, we propose a systematic investigation of the effects of chronic alcoholism on cerebellar morphology and function. Detoxified patients with chronic nonamnesic alcoholism, alcoholic Korsakoffs Syndrome (KS), and normal controls will be examined.
The aims of the study are 1) to quantify cerebellar integrity using quantitative magnetic resonance imaging (MRI); 2) to apply a component process approach to assess integrity of motor functions likely to be dependent upon cerebellar vs. motor cortical integrity; 3) to test selective brain structure-function relationships. The outcome of the three components of this revised proposal will provide 1) data on in vivo regional dysmorphology of the cerebellum and motor cortex associated with alcoholism, 2) a systematic description of motor deficits in equilibratory and non-equilibratory functions involving components of movement production, time perception, and motor skill learning, and 3) a rigorous attempt to understand functional ramifications of regional cerebellar and motor cortical dysmorphology in alcoholics. Knowledge of the extent and functional significance of alcoholic cerebellar pathology will lead to investigations of reversibility, and may ultimately guide rehabilitation efforts.
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