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: 8392945
• 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/8392945
• 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; 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检查 退伍军人酗酒的认知后果。滥用酒精是一种代价高昂且具有破坏性的行为 这个问题在美国退伍军人中普遍存在，其患病率几乎是一生中退伍军人的两倍半 非退伍军人的酒精相关疾病。我们的实验室率先使用了经典的眨眼法，或者 巴甫洛夫条件范式作为大脑神经病理变化的行为生物标志物 男性和女性酗酒者。我们在上一个资助期间的工作审查了经典的收购 条件性眨眼反应研究戒酒慢性酗酒者大量饮酒的后果 个人。这种范式基于巴甫洛夫条件反射作为基本学习单位的指标， 在动物模型中已充分记录了神经相关性，并且已证明自己对甚至对 人类神经心理疾病的微妙改变。我们的数据表明，戒酒者 这些经典条件性眨眼反应的获得受到不同程度的损害。现在，使用 先进的高分辨率成像和分析技术，我们已经开始识别与酒精相关的 使用扩散张量成像白质微观结构的退化并发现了关联 白质完整性与眨眼经典条件反射的表现之间的关系。初步数据还 揭示了与对照组参与者相比，酗酒者的双侧皮质厚度减少了 已知支持眨眼调节。本研究旨在确认并扩展这些 一项综合研究的初步观察结果，该研究检查了酗酒对大脑的影响 结构（使用组织微观结构和皮质厚度以及区域脑体积的 DTI 图来 表征灰质退化），以及这种退化对认知的相关影响 作为敏感行为生物标志物的眨眼经典条件反射的表现。脑血管升高 风险是重度饮酒的一种常见共病，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 风险可能会显着影响 在酗酒者中观察到的退化神经环境和相关的认知能力下降。这样我们就会 包括正常饮酒者的对照组，其 CVD 风险与重度酒精的分布相匹配 饮酒者评估 CVD 风险和酒精的独立和协同效应。成功者 完成所提出的目标将增加我们对酗酒神经心理学的了解 阐明小脑、内侧颞叶、额叶皮层和底层白细胞的相对作用 很重要，因为它们与在非常容易理解的背景下获得新的学习有关 学习任务。我们感受到了大脑结构的假设变化以及新的相关损伤 学习是酗酒所特有的一些棘手行为问题的根源。