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ISBRA 2004 AbstractsStanford University School of Medicine, Stanford, CA
IN VIVO DETECTION OF MACROSTRUCTURAL AND MICROSTRUCTURAL MARKERS OF BRAIN INTEGRITY IN HUMAL ALCOHOLISM AND A RODENT MODEL OF ALCOHOLISM
Adolf Pfefferbaum, M.D., Director, Neuroscience Program, SRI International, Menlo Park, CA 94025, U.S.A. and Professor, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, U.S.A.
Severe focal brain white matter pathology is a hallmark of several alcoholism-related clinical syndromes, such as Marchiafava-Bignami disease and central pontine myelinolysis. In vivo and postmortem studies have also noted widespread white matter pathology as a typical feature in uncomplicated alcoholism. Controlled longitudinal MR strucutral imaging studies have revealed increase or decrease in gross white matter brain volume depending on alcohol abstinence or consumption by alcoholics. Because tissue volume recovery appears incomplete with abstinence, alcoholic brain pathology may have two components, one reflecting permanent change and one transient change. In addition to bulk changes in white matter volume, the microstructural integrity of white matter can be examined in vivo with MR diffusion tensor imaging (DTI). With DTI, disruption of regional white matter has been noted in alcoholic men, and the extent of the abnormality correlates with performance on tests of working memory and attention. DTI has also detected abnormalities in brain white matter in alcoholic women not detectable with gross measures of structural size. Factors in addition to alcohol itself contribute to observed changes in brain tissue. Thiamine deficiency, for example, has been shown with animal models and by inference from patients with Wernicke-Korsakoff syndrome to account for myelin loss. Translational neuroimaging studies focused on animal models of alcoholism can complement human research and permit control of factors not possible in naturalistic human study. Our initial MRI and MRS investigations have yielded novel data on both chronic and acute alcohol exposure of alcohol-preferring rats and indicate substantial brain structural and metabolic variability that may underlie individual differences in alcoholism's untoward effects on brain structure and function.
