We propose to continue using magnetic resonance imaging (MRI), neuropsychological (NP), and event-related potential (ERP) testing to extend and refine our findings of CNS deficits associated with chronic alcoholism and aging. Our MRI studies of alcoholic man reveal volume loss in cortical gray and white matter, corpus callosum, hippocampus, and mammillary bodies and enlargement of cortical sulci and lateral and third ventricles. Older alcoholic men have gray matter volume deficits particularly striking in the prefrontal cortex. Electrophysiologically, the latency of P300, a physiological index of cognitive speed, is prolonged in alcoholic men with an exaggerated prolongation in older alcoholics; further, P300 latency and indices of tissue loss are significantly associated in alcoholics. Neuropsychologically, alcoholic men show deficits in executive abilities, short-term memory, fluency, and visuospatial abilities and especially severe deficits in balance. Our longitudinal studies demonstrate recovery of gray matter volume with abstinence and further reduction of white matter volume with continued drinking. For this competitive renewal, we propose the following studies: Study 1: fMRI experiments of localized brain activation during performance of auditory and visual working memory tasks. This study is designed to determine whether alcoholics show a pattern of cortical activation during working memory that is different from that observed in controls, and whether underlying structural deficits influence the pattern of fMRI activation. Study 2: Visual ERP and NP experiments of interhemispheric transfer time designed to assess the functional significance of corpus callosal thinning. Study 3: Continuation of our ongoing longitudinal study of alcoholic and control women. This study is designed to identify cross-sectional patterns of sparing and loss, their interaction with age and their comparability to findings in alcoholic men. Cross-sectional findings will be examined longitudinally to determine their interaction with alcohol consumption and the normal course of aging and to assess the extent to which deficits normalize with sobriety or are exacerbated with continued drinking. Study 4: A new longitudinal study in a new sample of older alcoholic men and women and their controls in order to extend, with refined anatomical and new functional measures, earlier findings.
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