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：
7283250
负责人：
REGINA MCGLINCHEY
金额：
$ 27.52万
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

来源：
https://reporter.nih.gov/project-details/7283250
关键词：
Affect Alcohol abuse Alcoholism Alcohols Animals Anterior Atrophic Awareness Behavioral Biological Neural Networks Blinking Brain Brain Stem Brain region Cell Nucleus Cerebellar Nuclei Cerebellar cortex structure Cerebellar degeneration Cerebellum Cerebral cortex Characteristics Chronic Cognitive Complex Condition Conditioned Stimulus Cues Demyelinations Depth Development Diffusion Magnetic Resonance Imaging Discrimination Learning Equilibrium Gait Hippocampus (Brain)Human Image Impairment Individual Investigation Learning Magnetic Resonance Imaging Measures Medial Memory Modeling Motor Skills Nature Neurons Numbers Participant Pathology Performance Play Pontine structure Positron-Emission Tomography Prosencephalon Reaction Time Recording of previous events Relative (related person)Research Personnel Role Sampling Septal Nuclei Specific qualifier value Stimulus Structure System Techniques Thalamic structure Time Uncertainty Vestibular nucleus structure Visuospatial Wernicke Encephalopathy Wernicke-Korsakoff Syndrome alcohol effect alcohol misuse classical conditioning cognitive change conditioning drinking executive function frontal lobe frontal lobe function in vivo indexing interest midbrain central gray substance neural circuit neuroimaging neuropathology neuropsychological oculomotor problem drinker programs relating to nervous system research study response white matter

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.

陈述（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Eyceblink关联学习任务中获取，表达和保留条件反应的能力。我们已经对相对简单的Eykeblink经典调节任务进行了几项研究，并在先前的研究中戒酒，并建议使用更具挑战性和信息丰富的Eyceblink关联学习任务来扩展这一研究。在过去的调查中，我们发现了我们归因于小脑萎缩的条件反应的学习和时机的损害，这是长期滥用酒精后通常是典型的。但是，实际上尚不清楚它们的缺陷在多大程度上仅归因于小脑萎缩，因为支持各种形式的EykeBlink经典条件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，以及这些区域也受到酒精的影响。我们进一步建议将这些发现与潜在的神经病理学（由MRI索引）和神经心理学功能联系起来。特别有趣的是，使用扩散量张量成像将眼神调节性能与潜在的白质相关联，以检查神经连通性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有助于其损害。拟议的调查使用了在非人类动物的神经网络水平上充分理解的经典8link链接调节任务，这将有助于我们进一步定义酒精中毒中关联学习障碍的程度，并开始揭示造成受损和保留学习的人类神经病理学。在形成新的联想记忆中提出的学习不足的根本性质可能对理解为什么控制滥用滥用所需的行为变化可能对这些人特别困难，这可能是至关重要的。