MR Studies of Alcohol-Induced Brain Injury and Recovery

描述（由申请人提供）：神经放射学方法显示慢性依赖有显著的脑和神经心理患者体积减少和神经行为缺陷。尽管在戒断期间某些改变会逆转，但持续超过解毒阶段的神经认知缺陷可能被视为发病前的危险因素和/或治疗结果的决定因素。我们之前的研究结果表明，需要验证的主要假设是：神经标记物n -乙酰天冬氨酸（NAA）在小脑蚓中的绝对浓度降低，以及手指敲击时大脑激活效率低下，都是结果不佳、早发病酒精依赖和神经认知/情感妥协的受试者额小脑回路中断的特征。这项工作的总体意义在于，它将利用最先进的MRI和MRS对大脑结构、代谢和激活的测量来解决关于神经认知/情感异常本质的新假设，这些异常可以（或不可以）通过戒断来逆转。我们建议确定在监测禁欲3个月后，自主节奏和外部节奏的食指敲击时小脑和运动皮质fMRI激活受损以及在执行Simon空间不相容任务时前额叶功能障碍是否有差异改善。其次，我们将评估任务表现和相应的fMRI激活在（练习/学习效果）和（恢复）fMRI会话之间是否区分患者和对照组。第三，我们将研究fMRI是否可以识别酒精依赖者和正常人之间小脑和额叶中功能差异的区域，为详细的MRS和结构MRI研究提供重点，这些研究可能会查明酗酒者大脑皮质-小脑回路中断的起源。最后，我们希望建立定量磁共振方法的预后价值，以预测神经认知/情感功能的恢复程度和三个月的禁欲的临床过程。这些对酒精引起的脑损伤的病理生理机制和戒酒恢复的研究具有重要的基础意义，对预防、诊断和治疗具有重要意义。

DESCRIPTION (provided by applicant): Neuroradiologic methods have shown that chronic dependent have significant reductions of brain and neuropsychological patients volume and neurobehavioral deficits. Whereas certain of these alterations reverse during abstinence, the neurocognitive deficts that persist beyond the phase of detoxification may be viewed as pre-morbid risk factors and/or determinants of treatment outcome. Our previous findings suggest the major hypothesis to be tested: Reduced absolute concentrations of the neuronal marker, N-acetylaspartate (NAA) in the cerebrellar vermis and inefficient brain activation during finger tapping both characterize disruption of fronto-cerbellar circuits in subject with poor outcome, early onset alcohol dependence and neurocognitive/affective compromise. The overall significance of the work proposed is that it will use complementary state of the art MRI and MRS measurements of brain structure, metabolism, and activation to address novel hypotheses regarding the nature of neurocognitive/affective abnormalities that either are (or are not) reversible with abstinence. We propose to determine whether impaired cerebellar and motor cortical fMRI activation during self-paced and externally paced index finger tapping with the dominant or nondominant hand and prefrontal dysfunction during performance of Simon spatial incompatibility task improve differentially over 3 months of monitored abstinence. Second, we will assess whether task performance and corresponding fMRI activation within (practice/learning effects) and between (recovery) fMRI sessions distinguish patients and controls. Third, we will study whether fMRI can identify regions in cerebellum and frontal lobes that are functionally discrepant between alcohol dependent and normal subjects to provide the focus for detailed MRS and structural MRI studies that may pinpoint the origin(s) of disruptions or corticocerebeUar circuits in alcoholics. Finally, we wish to establish the prognostic value of quantitative MR methods to predict the degree of recovery of neurocognitive/affective functions and clinical course over three months of abstinence. These investigations of pathophysiologic mechanisms underlying a alcohol-induced brain damage and recovery with abstinence are of fundamental importance, with implications for prevention, diagnosis and treatment.