This renewal application extends our prior work demonstrating subtle, yet quantitatively detectible, widespread white matter degradation wit h a frontal predilection in alcoholics. We propose that uncomplicated alcoholics also have subclinical variants of the more profound alcohol-related demyelinating conditions of Marchiafava-Bignami Disease (MBD), affecting corpus callosum, and Central Pontine Myelinolysis (CPM), affecting central pons. We propose to use structural magnetic resonance (MR) imaging wit h diffusion tensor imaging (DTI) and proton MR spectroscopy (MRS) to characterize affected brain regions in recovering, uncomplicated alcoholics and to identify functional liability exerted by disruption of selective white matter systems.
Specific Aim 1 will use DTI to examine the distribution of alcoholism-related brain white matter degradation and will test the hypothesis that low fractional anisotropy (FA) and high mean bulk diffusitivity (
Specific Aim 2 will use event-related potential (ERP) and behavioral tasks to examine the functional liability exerted by observed DTI abnormalities in splenium and genu of corpus callosum, longitudinal fasciculi, and frontal and occipital forceps in alcoholics.
Specific Aim 3 will use MRS to examine biochemical properties of callosal and pontine white matter in alcoholics and will test the hypotheses that relative to controls, alcoholics will exhibit shortened T2 of tissue-water and major proton metabolites in corpus callosum; pons tissue-water will have a prolonged T2; and high pons choline and normal NAA will support hypothesized demyelination without axonal deletion. Key to understanding how neuroadaptation to alcoholism-induced brain structural and functional deficits contributes to the self-sustaining nature of alcoholism is a detailed elucidation of alcoholism-induced brain damage and investigation of its functional consequences, the objective of this proposal.
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