Cognitive Changes Associated with Chronic Alcohol Abuse

与慢性酒精滥用相关的认知变化

基本信息

批准号：
6827070
负责人：
REGINA MCGLINCHEY
金额：
$ 28.88万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-25 至 2009-08-31
项目状态：
已结题

项目摘要

ESCRIPTION (provided by applicant): The primary aim of this proposal is to evaluate the ability of abstinent chronic alcoholics to acquire, express and retain conditioned responses during complex classical eyeblink associative learning tasks. We have conducted several investigations of associative learning using relatively simple eyeblink classical conditioning tasks with abstaining alcoholics in prior studies and propose to expand this line of investigation using more challenging and informative eyeblink associative learning tasks. In our past investigations, we have found impairments in the learning and timing of conditioned responses that we attributed to cerebellar atrophy that is typical following chronic misuse of alcohol. However, it is in fact unclear to what extent their deficits are attributable solely to cerebellar atrophy because the neural circuit that supports various forms of eyeblink classical conditioning involves additional regions of the forebrain such as the hippocampal system and frontal cortex, and these regions are also impacted by the effects of alcohol. We further propose to relate these findings to underlying neuropathology (as indexed by MRI) and neuropsychological function. Of particular interest will be to relate eyeblink conditioning performance to underlying white matter using diffusion tensor imaging to examine whether possible changes in neural connectivity are related to impaired learning. We will also investigate whether possible deficits in alcoholics' ability to become explicitly aware of stimulus contingencies contributes to their impairment. The proposed investigation, using classical eyeblink conditioning tasks that are well understood at the level of neural networks in nonhuman animals, will help us to further define the extent of associative learning impairment in alcoholics and begin to uncover the human neuropathology that is responsible for impaired and preserved learning. Gaining a comprehensive understanding of the underlying nature of the proposed learning deficit in the formation of new associative memories may be critical to understanding why the behavioral changes needed to control abusive drinking may be particularly difficult for these individuals.

描述（由申请人提供）：该提案的主要目的是评估戒酒的慢性酗酒者在复杂的经典眨眼联想学习任务中获得、表达和保留条件反应的能力。在之前的研究中，我们使用相对简单的眨眼经典条件反射任务和戒酒者对联想学习进行了几项调查，并建议使用更具挑战性和信息丰富的眨眼联想学习任务来扩展这一研究范围。在我们过去的研究中，我们发现条件反应的学习和时间安排受到损害，我们将其归因于小脑萎缩，这是长期滥用酒精后的典型症状。然而，事实上并不清楚它们的缺陷在多大程度上完全归因于小脑萎缩，因为支持各种形式的眨眼经典条件反射的神经回路涉及前脑的其他区域，例如海马系统和额叶皮层，并且这些区域也受酒精的影响。我们进一步建议将这些发现与潜在的神经病理学（如 MRI 索引）和神经心理功能联系起来。特别令人感兴趣的是使用扩散张量成像将眨眼调节性能与底层白质联系起来，以检查神经连接的可能变化是否与学习受损有关。我们还将调查酗酒者明确意识到刺激意外事件的能力的可能缺陷是否会导致他们的损害。拟议的研究使用在非人类动物的神经网络水平上很好理解的经典眨眼条件反射任务，将帮助我们进一步确定酗酒者联想学习障碍的程度，并开始揭示导致酗酒者联想学习障碍的人类神经病理学。保留学习。全面了解新联想记忆形成过程中所提出的学习缺陷的根本性质，对于理解为什么控制酗酒所需的行为改变对这些人来说可能特别困难至关重要。