This application for a competing renewal of a U01 cooperative agreement award is written in response to Program Announcement (PA) number PAR-11-282, International Research Collaboration on Alcohol and Alcoholism. Receipt of this award would enable us to continue a program of international collaborations among the well-established nationally funded research groups at INSERM/University of Caen site in France directed by Francis Eustache, Ph.D., the recently-established addictions research program at the Yonsei University affiliated Severance Hospital in Seoul, South Korea directed by Young-Chul Jung, M.D., Ph.D., and our longstanding neuroimaging and neuroscience laboratories funded principally by NIAAA, in the United States at Stanford University with Edith Sullivan, Ph.D., Principal Investigator (MPI) and at SRI International with Adolf Pfefferbaum, M.D. (MPI). The overarching aim of this collaboration is 1) to use neuroimaging, neuropsychology, and biomarkers of nutrition in alcoholics, with and without KS, and controls to compare and contrast the effects of alcohol on brain structure and function across nations and 2) to identify markers of nutritional status, genetic variants, and alcohol consumption patterns that modulate the principal dependent measures and explain heterogeneity in presentation and recovery of alcoholism.
Three specific aims with testable hypotheses are proposed: 1. Prospectively screen with common diagnostic DSM-V criteria 100 alcoholics, 100 controls, and 10 KS in each country-U.S., France, and South Korea-and acquire the following data: 1a. Neuroimaging (MRI, FLAIR, DTI, and rs-fMRI) data using common protocols developed over the current funding period. 1b. Neuropsychological data using the common long and newly developed short test batteries. 1c. Blood for analysis of biomarkers of nutritional status (hemogram for red blood cell count, hematocrit, hemoglobin, mean corpuscular volume; vitamin B1 (whole blood thiamine diphosphate), folate, B12 and cerebrovascular risk factor (homocysteine). 1.d. Blood for analysis of thiamine transporter genotyping 2. Implement a secure pipeline for data reception, storage, analysis, and dissemination to and from project sites. 3. Conduct data analysis and hypothesis testing in collaboration with the project scientists (French and Korean visiting the U.S. and U.S. visiting France and Korea) and export results and analysis procedures to France and Korea.

Public Health Relevance

of the proposed work is to identify biomarkers that indicate mechanisms of alcoholism's untoward effects on neural systems and their functions that account for the vast differences in the expression of these effects within and across ethnicities, cultures, and nations. The potential translational value of the research outcomes may be recognized in terms of behavioral, nutritional, and pharmacological therapeutic possibilities.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
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Neuroscience Review Subcommittee (AA)
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Matochik, John A
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Stanford University
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Fama, Rosemary; Le Berre, Anne-Pascale; Hardcastle, Cheshire et al. (2017) Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism. Addict Biol :
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
Le Berre, Anne-Pascale; Müller-Oehring, Eva M; Schulte, Tilman et al. (2017) Deviant functional activation and connectivity of the right insula are associated with lack of awareness of episodic memory impairment in nonamnesic alcoholism. Cortex 95:15-28
Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V (2017) Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research. Alcohol Clin Exp Res 41:1432-1443
Le Berre, Anne-Pascale; Sullivan, Edith V (2016) Anosognosia for Memory Impairment in Addiction: Insights from Neuroimaging and Neuropsychological Assessment of Metamemory. Neuropsychol Rev 26:420-431
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
Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra et al. (2015) Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States. Front Hum Neurosci 9:354
Nichols, B Nolan; Pohl, Kilian M (2015) Neuroinformatics Software Applications Supporting Electronic Data Capture, Management, and Sharing for the Neuroimaging Community. Neuropsychol Rev 25:356-68
Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf et al. (2015) Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease. Brain Imaging Behav 9:619-38

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