US-France Research Collaboration on Neuroimaging Studies of Alcoholism

描述（由申请人提供）：U 01合作协议奖的申请是为了响应计划公告（PA）编号PAR-08-004，“酒精和酒精中毒国际研究合作”。“该奖项将使法国的两个CNOM站点（奥赛和卡昂）与我们的美国神经科学实验室之间的国际合作能够调查慢性酒精中毒对中枢神经系统结构和功能的影响。我们的国际合作提供了一个独特的机会，检查内和跨文化的变化，广泛的酒精中毒相关的神经病理学，在体内测量与结构磁共振成像（MRI）;大脑微观结构，电路和组织质量，测量与扩散张量成像（DTI）;和选择性脑功能，通过功能性磁共振成像（fMRI）和认知、记忆和运动能力组成过程的神经心理学测试来测量。人类酒精中毒对大脑结构和功能的影响具有相当大的异质性。这个多站点项目将是一个有效的方法来测试的总体假设，即酒精对大脑结构和功能的异质性的后果是由于酒精使用模式，营养状况和戒断症状的历史的个体差异。在美国和法国，目标受试者样本将涵盖从单纯性酗酒者到患有严重遗忘症的Korsakoff综合征（KS）的临床表现，并将能够测试有关导致酗酒神经病理学异质性的因素的假设。该提案的具体目标是1.确定三类临床变量的影响-饮酒模式，营养史和状态，和戒断史-a）根据在美国和法国收集的具有分级症状严重程度的酗酒者的遗留和前瞻性MRI数据测量的酗酒相关脑畸形B）酗酒-相关白色物质赤字测量遗留和前瞻性DTI数据收集在美国和法国的酗酒者与分级症状严重程度2。在美国开发并出口到法国的fMRI和DTI方案，旨在检查和分离a）认知额小脑和额叶运动回路B）边缘回路中断，以区分外显记忆中的编码和提取缺陷。

DESCRIPTION (provided by applicant): 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.