US-France Research Collaboration on Neuroimaging Studies of Alcoholism

描述(由申请人提供)：本U01合作协议奖的申请是对项目公告(PA)编号PAR-08-004“国际酒精和酒精中毒研究合作”的回应。该奖项将使INSERM在法国的两个地点(奥赛和卡昂)与我们的美国神经科学实验室开展国际合作，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，可以在文化差异内和跨文化差异中检查一系列与酒精依赖相关的神经病理，通过结构磁共振成像(MRI)在体内测量；通过扩散张量成像(DTI)测量大脑微观结构、电路和组织质量；以及通过功能磁共振(FMRI)和认知、记忆和运动能力的组成部分过程的神经心理测试测量选择性脑功能。人类酗酒的特点是其对大脑结构和功能的影响具有相当大的异质性。这一多地点项目将是检验最重要的假设的有效方法，该假设认为酒精对大脑结构和功能的异质性实质上是由于酒精使用模式、营养状况和戒断症状史的个体差异。在美国和法国，目标受试者样本将涵盖临床表现，从简单的酗酒者到患有严重健忘症的Korsakoff综合征(KS)，并将能够测试有关导致酒精中毒神经病理异质性的因素的假说。这项建议的具体目标是：1.确定三类临床变量--饮酒模式、营养史和状况以及戒断史--对酒精中毒相关脑畸形的影响。a)根据在美国和法国从症状严重程度分级的酒鬼那里收集的遗留和预期的MRI数据测量与酒精中毒相关的脑畸形；b)根据在美国和法国收集的症状严重程度分级的酒精患者的遗留和预期DTI数据测量与酒精中毒相关的脑白质缺陷。在美国开发并向法国出口旨在检查和分离a)认知性额小脑和前额运动神经回路的fMRI和DTI方案。b)边缘回路中断，以区分显性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.