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: 7797119
• 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 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797119
• 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

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Relevance to VA Patient Care Mission Alcohol abuse is a costly and functionally devastating problem that is pervasive among America's veterans. Prevalence rates of alcohol-related disorders among veterans are nearly two and a half times the lifetime prevalence of alcohol-related disorders of nonveterans. Because of the direct impact alcohol may have on cognitive function and treatment, there is a fundamental need for a more complete understanding of the cognitive sequelae of alcohol use and misuse in both male and female veterans. Using classical conditioning methods, our data demonstrate that abstinent alcoholics are differentially impaired in the acquisition of these classically conditioned eyeblink responses and suggest that the pattern of deficits observed may underlie some of the intractable behavioral problems that characterize alcoholism.

描述（由申请人提供）： 摘要该建议代表了我们实验室为研究退伍军人酗酒后果的一系列工作的延续。酒精滥用是一个昂贵且功能上毁灭性的问题，在美国退伍军人中普遍存在，是非退伍军人与酒精相关疾病的终生患病率的近两倍。我们的实验室率先使用了Ekeyblink经典或Pavlovian的使用，将范式调节范式作为男性和女性酒精中毒大脑神经病理学变化的行为生物标志物。我们从前的资金期开始的工作检查了对经典条件的呼吸链接反应的获取，以研究戒除慢性酒精饮酒的大量饮酒的后果。这种范式基于帕夫洛夫条件作为基本学习单位的指数，在动物模型中已经有充分的神经相关性，并且证明自己对人类神经心理障碍的微妙变化非常敏感。我们的数据表明，在获取这些经典条件的眼睛闪烁反应时，禁忌的酗酒者会受到差异性损害。现在，使用先进的高分辨率成像和分析技术，我们已经开始使用扩散张量成像来鉴定与酒精相关的白质微观结构的变性，并发现白质完整性与Eykeblink经典条件上的性能之间的关联。初步数据还显示，与已知可以支持眼神调节的大脑区域的对照参与者相比，酒精中毒的双侧皮质厚度减少。 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.脑血管风险升高是大量酒精使用的常见合并症，它会影响许多相同的大脑区域和受虐待影响的认知功能。合并症CVD风险可能对酗酒者观察到的退化性神经环境以及相关的认知下降产生重大贡献。因此，我们将包括一个对照组的普通饮酒者，这些对照者对重量饮酒者的CVD风险分布匹配，以评估CVD风险和酒精的独立和协同作用。提出的目标的成功完成将通过阐明小脑，内侧颞叶，额叶皮层和基本的白质的相对作用，从而增加我们对酒精中毒神经心理的了解，因为它们与在一项非常了解学习任务的上下文中与新学习有关。我们认为，新学习的大脑结构和相关障碍的假设变化是酗酒的一些棘手的行为问题。 公共卫生相关性： 与VA患者护理任务相关的酒精滥用是一个昂贵且功能上毁灭性的问题，在美国的退伍军人中普遍存在。退伍军人中与酒精相关疾病的患病率是非退伍军人与酒精相关疾病的终生患病率的差不多两倍。由于酒精可能对认知功能和治疗产生直接影响，因此对男性和女性退伍军人的酒精使用和滥用的认知后遗症的基本需求。使用经典的调节方法，我们的数据表明，在获取这些经典条件的Eykeblink反应时，禁欲的酒精饮料会受到差异性，并表明所观察到的缺陷模式可能是某些特征在于酒精中毒的棘手的行为问题。