This application for a U01 cooperative agreement award is in response to Program Announcement (PA) number PAR-08-004, "International Research Collaboration on Alcohol and Alcoholism." The award will enable an international collaboration between two INSERM sites in France (Orsay and Caen) and our US neuroscience laboratories to investigate the consequences of chronic alcoholism on central nervous system structure and function. Our international collaboration provides a unique opportunity to examine within and across cultural variation a broad range of alcoholism-related neuropathology, measured in vivo with structural magnetic resonance imaging (MRI);brain microstructure, circuitry, and tissue quality, measured with diffusion tensor imaging (DTI);and selective brain functions, measured with functional MRI (fMRI) and neuropsychological tests of component processes of cognition, memory, and motor abilities. Human alcoholism is marked by considerable heterogeneity in its consequences on brain structure and function. This multi-site project will be an efficient approach for testing the overarching hypothesis that the heterogeneity of alcoholic consequences on brain structure and function are due substantially to individual differences in pattern of alcohol use, nutritional status, and history of withdrawal symptoms. In both the US and France, the target subject samples will span clinical manifestations from uncomplicated alcoholics to those with the profound amnesia of Korsakoff's Syndrome (KS) and will enable testing of hypotheses about factors contributing to the heterogeneity of alcoholism neuropathology.
The Specific Aims of this proposal are to 1. Determine the influence of three classes of clinical variables-drinking pattern, nutritional history and status, and withdrawal history-on a) Alcoholism-related brain dysmorphology measured on legacy and prospective MRI data collected in the US and France from alcoholics with graded symptom severity b) Alcoholism-related white matter deficits measured on legacy and prospective DTI data collected in the US and France in alcoholics with graded symptom severity 2. Develop in the US and export to France fMRI and DTI protocols designed to examine and dissociate a) Cognitive frontocerebellar and frontal motor circuitry b) Limbic circuitry disruption to distinguish encoding from retrieval deficits in explicit memory.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAA1-CC (12))
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Matochik, John A
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Stanford University
Schools of Medicine
United States
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Jung, Young-Chul; Schulte, Tilman; Müller-Oehring, Eva M et al. (2014) Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics. Psychopharmacology (Berl) 231:4443-53
Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra et al. (2014) Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: comparison of effects in France and the United States. Hum Brain Mapp 35:4635-53
Chanraud, Sandra; Pitel, Anne-Lise; Muller-Oehring, Eva M et al. (2013) Remapping the brain to compensate for impairment in recovering alcoholics. Cereb Cortex 23:97-104
Pitel, Anne-Lise; Chanraud, Sandra; Muller-Oehring, Eva M et al. (2013) Modulation of limbic-cerebellar functional connectivity enables alcoholics to recognize who is who. Brain Struct Funct 218:683-95
Pitel, Anne-Lise; Chanraud, Sandra; Rohlfing, Torsten et al. (2012) Face-name association learning and brain structural substrates in alcoholism. Alcohol Clin Exp Res 36:1171-9
Colrain, Ian M; Sullivan, Edith V; Rohlfing, Torsten et al. (2011) Independent contributions of cortical gray matter, aging, sex and alcoholism to K-complex amplitude evoked during sleep. Sleep 34:787-95
Pfefferbaum, Adolf; Chanraud, Sandra; Pitel, Anne-Lise et al. (2011) Cerebral blood flow in posterior cortical nodes of the default mode network decreases with task engagement but remains higher than in most brain regions. Cereb Cortex 21:233-44
Pitel, Anne-Lise; Zahr, Natalie M; Jackson, Karen et al. (2011) Signs of preclinical Wernicke's encephalopathy and thiamine levels as predictors of neuropsychological deficits in alcoholism without Korsakoff's syndrome. Neuropsychopharmacology 36:580-8
Chanraud, Sandra; Pitel, Anne-Lise; Rohlfing, Torsten et al. (2010) Dual tasking and working memory in alcoholism: relation to frontocerebellar circuitry. Neuropsychopharmacology 35:1868-78
Pitel, Anne-Lise; Chanraud, Sandra; Sullivan, Edith V et al. (2010) Callosal microstructural abnormalities in Alzheimer's disease and alcoholism: same phenotype, different mechanisms. Psychiatry Res 184:49-56

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