Sleep EEG and MRI Markers of Brain Recovery with Alcohol Abstinence

戒酒后大脑恢复的睡眠脑电图和 MRI 标记

• 批准号: 8177112
• 负责人: Ian Michael Colrain
• 金额: $ 25.55万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8177112
• 关键词: Abstinence; Accounting; Address; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Anisotropy; Biological Markers; Brain; Brain region; Characteristics; Chronic; Complex; Data; Deterioration; Diffusion Magnetic Resonance Imaging; EP300 gene; Electroencephalography; Evaluation; Family history of; Frequencies; Laboratories; Magnetic Resonance Imaging; Measures; Mediating; Metric; Nervous System Physiology; Nervous system structure; Neuraxis; Neurologic; Neurons; Pathway interactions; Pattern; Physiological; Production; Psychological reinforcement; REM Sleep; Recovery; Recovery of Function; Relapse; Relative (related person); Reporting; Resolution; Role; Scalp structure; Site; Sleep; Sleep Architecture; Sleep disturbances; Slow-Wave Sleep; Source; Staging; Structure; System; Techniques; Testing; Time; Ventricular; Woman; Work; alcohol abstinence; alcohol exposure; drinking; frontal lobe; gray matter; improved functioning; in vivo; indexing; innovation; men; neuromechanism; neurophysiology; non rapid eye movement; novel; partial recovery; physical conditioning; problem drinker; response; sex; sobriety; trait; white matter

DESCRIPTION (provided by applicant): Scalp recorded EEG delta activity during sleep is homeostatically regulated and has important roles in maintaining neurological and physical health. Low levels of delta activity are part of the ubiquitous sleep disturbance in alcoholics. Deficient sleep delta activity has been shown to predict relapse due to the reinforcement of drinking produced by the perceived improvement of sleep following resumption of alcohol consumption. We have previously identified evoked EEG delta frequency responses during sleep as a novel and sensitive state marker of neurophysiologic function in alcoholic men and women. The responses are predominant over frontal brain regions, appear independent of family history of alcohol abuse and are modulated by periods of abstinence. The production of high amplitude EEG responses require the highly synchronized firing of large numbers of healthy neurons, and thus address two aspects of known negative consequences of alcoholism: loss of gray matter and degradation of white matter tracts in the brain. Importantly, there is growing evidence that both gray and white matter may show at least partial recovery with abstinence. This application thus proposes to evaluate the neural mechanisms that are negatively impacted by alcohol abuse, which also show recovery with abstinence and underlie sleep delta activity such as the K- complex (KC). Unique to this application is the combined assessment of high resolution brain structure, microstructural integrity of white matter tracts, and sleep EEG measures of neurophysiology; all using safe and non-invasive techniques. These data will permit an assessment of patterns of degradation and sparing of brain systems following chronic alcohol exposure, and an assessment of structural and functional recovery with abstinence from drinking. The proposal has two major specific aims: Aim 1: Determine relative contributions of white matter and gray matter changes to evoked KC amplitude in recently sober alcoholics and matched controls. These data will permit evaluation of the role of white matter microstructural degradation in the reduction in evoked delta EEG amplitude in alcoholics. Aim 2: To determine the time course of the abstinence-related recovery in evoked KC amplitude in alcoholics and the role of white matter and gray matter changes in the recovered EEG responses. The hypothesis to be tested is that abstinent alcoholics will show recovery in indices of brain structural and functional integrity over time, while alcoholics who continue to drink or who relapse will show continued decline, and controls will show little or no change. The proposed innovative study will be the first to combine sleep EEG, structural MRI and Diffusion Tensor Imaging to evaluate mechanisms of brain degradation with alcohol abuse; and to track brain recovery with abstinence. The work will help establish metrics of the capacity of brain recovery with abstinence. PUBLIC HEALTH RELEVANCE: Alcoholics who continue to drink sustain ongoing deterioration in central nervous system (CNS) structure and function, including long lasting disruption of sleep. With cessation of drinking, partial recovery of brain function can be attained. This study will assess the brain macrostructural and microstructural underpinnings of a novel index of sleep EEG and its utility as a biological marker of CNS recovery with abstinence from drinking.

描述（由申请人提供）：睡眠期间头皮记录的EEG Delta活动受体内稳态调节，并且在维持神经和身体健康方面具有重要作用。三角洲活性水平低是酗酒者无处不在的睡眠障碍的一部分。不足的睡眠三角洲活性已被证明可以预测，由于恢复饮酒后，由于感知到的睡眠改善所产生的饮酒而导致的复发。我们先前曾确定睡眠期间诱发的脑电图频率反应是酗酒的男性和女性神经生理功能的新颖和敏感的状态标记。这些反应主要是额叶大脑区域，似乎独立于酒精滥用的家族史，并且受禁欲时期的调节。高振幅脑电图反应的产生需要大量健康神经元的高度同步发射，因此解决了酒精中毒的已知负面后果的两个方面：灰质的丧失和大脑中白质区的降解。重要的是，越来越多的证据表明，灰质和白质都可能表现出至少避免的部分恢复。因此，该应用建议评估酗酒对酗酒产生负面影响的神经机制，这些神经机制也表现出戒酒的恢复和睡眠三角洲活性（例如K-Complex（KC））的基础。该应用独有的是对高分辨率大脑结构，白质区的微结构完整性的综合评估以及神经生理学的睡眠脑电图测量。所有这些都使用安全和非侵入性技术。这些数据将允许评估慢性酒精暴露后脑系统降解和保留的模式，并评估结构和功能恢复，并禁止饮酒。该提案具有两个主要的特定目的：目标1：确定白质和灰质变化对最近清醒的酒精和匹配控制中诱发的KC振幅的相对贡献。这些数据将允许评估白质微观结构降解在戒酒中诱发的三角洲eeg振幅减少中的作用。 目标2：确定戒酒幅度在酗酒中的戒酒相关恢复的时间过程以及白质和灰质变化在恢复的脑电图反应中的作用。要检验的假设是，随着时间的流逝，戒酒的酗酒者将显示出大脑结构和功能完整性指数的恢复，而酗酒者继续喝酒或复发会持续下降，并且控制措施几乎没有变化或没有变化。拟议的创新研究将是第一个结合睡眠脑​​电图，结构性MRI和扩散张量成像，以评估用酗酒的脑降解机制。并以禁欲跟踪大脑恢复。这项工作将有助于建立戒酒能力的指标。 公共卫生相关性：继续饮酒的酗酒者中枢神经系统（CNS）结构和功能的持续恶化，包括持久的睡眠中断。随着饮酒的停止，可以部分恢复大脑功能。这项研究将评估新型睡眠脑电图指数的大脑宏观结构和微观结构基础及其作为CNS恢复的生物学标志物，并禁止饮酒。