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 (), measures of white matter integrity, are widespread in alcoholics but have a frontal predilection.
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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neurotoxicology and Alcohol Study Section (NAL)
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Witt, Ellen
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Sri International
Menlo Park
United States
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Park, Sang Hyun; Zhang, Yong; Kwon, Dongjin et al. (2018) Alcohol use effects on adolescent brain development revealed by simultaneously removing confounding factors, identifying morphometric patterns, and classifying individuals. Sci Rep 8:8297
Chen, Geng; Dong, Bin; Zhang, Yong et al. (2018) Angular Upsampling in Infant Diffusion MRI Using Neighborhood Matching in x-q Space. Front Neuroinform 12:57
Zahr, Natalie M; Pfefferbaum, Adolf; Sullivan, Edith V (2017) Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders. Neuropharmacology 122:189-200
Schulte, T; Jung, Y-C; Sullivan, E V et al. (2017) The neural correlates of priming emotion and reward systems for conflict processing in alcoholics. Brain Imaging Behav 11:1751-1768
Yang, Zhanlong; Chen, Geng; Shen, Dinggang et al. (2017) Robust Fusion of Diffusion MRI Data for Template Construction. Sci Rep 7:12950
Chen, Geng; Dong, Bin; Zhang, Yong et al. (2017) q-Space Upsampling Using x-q Space Regularization. Med Image Comput Comput Assist Interv 10433:620-628
Chen, Geng; Dong, Bin; Zhang, Yong et al. (2017) Neighborhood Matching for Curved Domains with Application to Denoising in Diffusion MRI. Med Image Comput Comput Assist Interv 10433:629-637
Maumet, Camille; Auer, Tibor; Bowring, Alexander et al. (2016) Sharing brain mapping statistical results with the neuroimaging data model. Sci Data 3:160102
Le Berre, Anne-Pascale; Müller-Oehring, Eva M; Kwon, Dongjin et al. (2016) Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates. Cortex 81:192-202
Alba-Ferrara, L; Müller-Oehring, E M; Sullivan, E V et al. (2016) Brain responses to emotional salience and reward in alcohol use disorder. Brain Imaging Behav 10:136-46

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