US-France Research Collaboration on Neuroimaging Studies of Alcoholism

描述（由申请人提供）：本U01合作协议奖申请是为了响应项目公告（PA）编号PAR-08-004，“酒精和酒精中毒国际研究合作”。该奖项将使INSERM在法国的两个站点（Orsay和Caen）与我们在美国的神经科学实验室之间进行国际合作，研究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来检查内部和跨文化差异的广泛的酒精相关的神经病理学，在体内测量的结构磁共振成像（MRI）；用弥散张量成像（DTI）测量大脑微结构、电路和组织质量；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。这个多地点项目将是检验酒精对大脑结构和功能影响的异质性主要是由于酒精使用模式、营养状况和戒断症状史的个体差异这一首要假设的有效方法。在美国和法国，目标受试者样本将跨越临床表现，从简单的酗酒者到那些患有科尔萨科夫综合征（KS）的深度健忘症的人，并将能够测试导致酒精中毒神经病理学异质性的因素的假设。本建议的具体目标是：1。确定三类临床变量（饮酒模式、营养史和状态以及戒断史）对以下因素的影响：a)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数据中测量的酒精相关脑畸形；b)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DTI数据中测量的酒精相关白质缺陷2。在美国开发并向法国出口fMRI和DTI方案，旨在检查和分离a)认知额小脑和额运动回路b)边缘回路中断，以区分编码和外显记忆中的检索缺陷。

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.