MR Studies of Alcohol-Induced Brain Injury and Recovery

描述（由申请人提供）：神经放射学方法表明，慢性依赖性患者的大脑和神经心理学体积和神经行为缺陷显着减少。尽管这些改变中的某些在戒断期间会逆转，但在戒毒阶段之后持续存在的神经认知缺陷可能被视为病前危险因素和/或治疗结果的决定因素。我们之前的研究结果提出了要测试的主要假设：小脑蚓部中神经元标记物 N-乙酰天冬氨酸 (NAA) 的绝对浓度降低以及手指敲击期间大脑激活效率低下，都是结果不佳、早发性酒精依赖和神经认知/情感妥协的受试者额小脑回路破坏的特征。这项工作的总体意义在于，它将使用最先进的 MRI 和 MRS 测量大脑结构、代谢和激活来解决有关神经认知/情感异常性质的新假设，这些异常可以（或不可）通过禁欲逆转。我们建议确定在自定速和外部定速食指敲击过程中用优势手或非优势手敲击时受损的小脑和运动皮质功能磁共振成像激活以及在西蒙空间不相容性任务执行过程中前额叶功能障碍是否在3个月的禁欲监测中有所改善。其次，我们将评估任务表现和相应的功能磁共振成像激活（练习/学习效果）和功能磁共振成像课程之间（恢复）是否能够区分患者和对照组。第三，我们将研究功能磁共振成像是否可以识别酒精依赖者和正常受试者之间功能差异的小脑和额叶区域，为详细的MRS和结构MRI研究提供焦点，这些研究可能查明酗酒者皮质小脑回路中断的起源。最后，我们希望建立定量 MR 方法的预后价值，以预测戒断三个月后神经认知/情感功能的恢复程度和临床病程。这些对酒精引起的脑损伤和戒酒恢复的病理生理机制的研究具有根本重要性，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.