Classical Associative Learning in Male and Female Alcoholics

男性和女性酗酒者的经典联想学习

• 批准号: 8195958
• 负责人: REGINA MCGLINCHEY
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8195958
• 关键词: Affect; Alcohol abuse; Alcohol consumption; Alcohol-Related Disorders; Alcoholism; Alcohols; Americas; Animal Model; Animals; Anisotropy; Behavioral; Bilateral; Biological Markers; Blinking; Brain; Brain region; Cerebellar degeneration; Cerebellum; Chronic; Cognition; Cognitive; Complex; Control Groups; Critical Pathways; Data; Deterioration; Diabetes Mellitus; Diffusion; Diffusion Magnetic Resonance Imaging; Discrimination; Discrimination Learning; Disease; Environment; Female; Funding; Head; Health; Heavy Drinking; Human; Hypertension; Image Analysis; Impaired cognition; Impairment; Individual; Laboratories; Learning; Literature; Magnetic Resonance Imaging; Maps; Measures; Medial; Mediating; Methods; Mission; Neuropsychological Tests; Neuropsychology; Outcome; Participant; Patient Care; Pattern; Performance; Prevalence; Problem behavior; Procedures; Production; Recording of previous events; Relative (related person); Research; Resolution; Reversal Learning; Risk; Role; Short-Term Memory; Statistical Models; Structure; Surface; System; Techniques; Temporal Lobe; Testing; Thalamic structure; Thick; Time; Tissues; Variant; Veterans; Work; abstracting; alcohol misuse; alcohol risk; base; brain behavior; brain volume; cerebrovascular; classical conditioning; cognitive function; cognitive system; conditioning; executive function; frontal lobe; gray matter; indexing; interest; male; morphometry; neuropsychological; problem drinker; relating to nervous system; response; statistics; white matter

Abstract This proposal represents a continuation of a body of work that our laboratory has undertaken to examine the cognitive consequences of alcohol abuse in veterans. Alcohol misuse is a costly and functionally devastating problem that is pervasive among America's veterans, with nearly two and a half times the lifetime prevalence of alcohol-related disorders of nonveterans. Our laboratory has pioneered the use of the eyeblink classical, or Pavlovian, conditioning paradigm as a behavioral biomarker for neuropathological changes in the brain of male and female alcoholics. Our work from the prior funding period examined the acquisition of classically conditioned eyeblink responses to study the consequences of heavy drinking in abstinent chronic alcoholic individuals. This paradigm, based on Pavlovian conditioning as an index of a fundamental unit of learning, has well documented neural correlates in animal models, and has proven itself to be very sensitive to even subtle alterations in human neuropsychological disorders. Our data demonstrate that abstinent alcoholics are differentially impaired in the acquisition of these classically conditioned eyeblink responses. Now, using advanced high resolution imaging and analysis techniques, we have begun to identify alcohol-related degeneration of white matter microstructure using diffusion tensor imaging and have found associations between white matter integrity and performance on eyeblink classical conditioning. Preliminary data also reveal bilateral cortical thickness reductions in alcoholics compared to control participants in brain regions that are known to support eyeblink conditioning. The present study proposes to confirm and extend these preliminary observations in a comprehensive study examining the impact of heavy alcohol use on brain structure (using DTI maps of tissue microstructure and cortical thickness and regional brain volumes to characterize gray matter deterioration), and the associated impact of this deterioration on cognition using performance on eyeblink classical conditioning as a sensitive behavioral biomarker. Elevated cerebrovascular risk is a common comorbid condition of heavy alcohol use that impacts many of the same brain regions and cognitive functions that are impacted by abuse. It is likely that comorbid CVD risk contributes significantly to the degenerative neural environment and associated cognitive decline observed in alcoholics. Thus we will include a control group of normal drinkers with a matched distribution of CVD risk to the heavy alcohol drinkers to evaluate the independent and synergistic effects of CVD risk and alcohol. The successful completion of the aims proposed will add to our knowledge of the neuropsychology of alcoholism by clarifying the relative roles of the cerebellum, medial temporal lobe, frontal cortex and underlying white matter as they relate to the acquisition of new learning within the context of an extremely well understood learning task. We feel the hypothesized changes in brain structure and associated impairments in new learning underlie some of the intractable behavioral problems that characterize alcoholism.

抽象的 该提案代表了我们实验室为研究的一项工作的延续 酗酒对退伍军人的认知后果。滥用酒精是一种昂贵且功能上的毁灭性 在美国退伍军人中普遍存在的问题，一生患病率是近两倍半 非退伍军人的酒精相关疾病。我们的实验室率先使用了Eykeblink古典或 帕夫洛维亚人，将范式作为一种行为生物标志物，用于大脑的神经病理学变化 男性和女性酗酒者。我们从上前资金期开始的工作检查了对经典的收购 有条件的眉毛反应，以研究戒酒中大量饮酒的后果 个人。这种范式基于帕夫洛维亚条件作为基本学习单位的指数， 在动物模型中有充分记录的神经相关性，并且证明自己对 人类神经心理障碍的细微变化。我们的数据表明，戒酒是 在获取这些经典条件的透明响应时，差异障碍。现在，使用 高级高分辨率成像和分析技术，我们已经开始识别与酒精有关的 使用扩散张量成像的白质微观结构的变性，并发现了关联 在白质的完整性和8lekellink经典条件上的性能之间。也是初步数据 与大脑区域的对照参与者相比 已知可以支持眉毛调节。本研究建议确认并扩展这些 在一项综合研究中，研究大量酒精对大脑的影响 结构（使用组织微观结构和皮质厚度和区域脑体积的DTI图 表征灰质的恶化），以及这种恶化对认知的影响 在拒绝经典条件上作为敏感行为生物标志物的性能。脑血管升高 风险是大量饮酒的常见状态，会影响许多相同的大脑区域和 受虐待影响的认知功能。合并CVD风险可能会大大贡献 酗酒者观察到的退化性神经环境和相关的认知下降。这样我们就会 包括一个对照组的正常饮酒者 饮酒者评估CVD风险和酒精的独立和协同作用。成功 提出的目标的完成将增加我们对酒精中毒神经心理学的了解 阐明小脑，内侧颞叶，额叶皮层和下面白色的相对作用 当它们与在非常有理由的背景下获得新学习有关的事情 学习任务。我们认为大脑结构的假设变化以及新的损害 学习的基础是酗酒的一些棘手的行为问题。