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 δ活动是稳态调节的，在维持神经和身体健康方面具有重要作用。低水平的δ活动是酗酒者普遍存在的睡眠障碍的一部分。睡眠δ活动不足已被证明可以预测复发，这是由于恢复饮酒后睡眠的改善所产生的饮酒强化。我们以前已经确定了诱发脑电图δ频率反应在睡眠中作为一种新的和敏感的状态标记的神经生理功能的酗酒的男性和女性。这些反应在额叶脑区占主导地位，似乎独立于酗酒的家族史，并受到禁欲时期的调制。高振幅EEG响应的产生需要大量健康神经元的高度同步的放电，并且因此解决了已知的酒精中毒的负面后果的两个方面：大脑中灰质的损失和白色物质束的退化。重要的是，越来越多的证据表明，灰色和白色物质都可能在禁欲后至少部分恢复。因此，本申请提出评估受酒精滥用负面影响的神经机制，其也显示出戒断的恢复和睡眠δ活性的基础，例如K复合物（KC）。该应用程序的独特之处在于对高分辨率脑结构、白色物质束的微结构完整性和神经生理学的睡眠EEG测量进行综合评估;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模式的退化和保留的大脑系统慢性酒精暴露后，和结构和功能的恢复与戒酒的评估。该建议有两个主要的具体目标：目标1：确定相对贡献的白色物质和灰质的变化诱发KC振幅在最近清醒的酗酒者和匹配的控制。这些数据将允许评估的作用，白色物质的微结构退化的减少诱发δ脑电图振幅酗酒。 目标二：探讨酒精依赖者戒断后诱发KC波幅恢复的时间过程，以及白色物质和灰质改变在恢复后EEG反应中的作用。待检验的假设是，戒酒的酗酒者随着时间的推移，大脑结构和功能完整性的指数将显示出恢复，而继续饮酒或复发的酗酒者将显示出持续下降，对照组将显示出很少或没有变化。这项拟议中的创新研究将是第一个将联合收割机睡眠脑电图、结构磁共振成像和扩散张量成像结合起来的研究，以评估酗酒导致大脑退化的机制;并跟踪戒酒后的大脑恢复情况。这项工作将有助于建立禁欲大脑恢复能力的指标。 公共卫生关系：持续饮酒的酗酒者会持续中枢神经系统（CNS）结构和功能的恶化，包括长期持续的睡眠中断。停止饮酒可以使大脑功能部分恢复。本研究将评估一种新的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戒酒后中枢神经系统恢复的生物标志物的效用。