Sleep EEG and MRI Markers of Brain Recovery with Alcohol Abstinence

描述（由申请人提供）：睡眠期间记录的头皮EEG δ活动是动态调节的，在维持神经和身体健康方面具有重要作用。低水平的delta活动是酗酒者普遍存在的睡眠障碍的一部分。睡眠delta活动不足已被证明可以预测复发，因为在恢复饮酒后，由于感知到睡眠改善而产生的饮酒强化。我们之前已经发现睡眠期间诱发的脑电图δ频率反应是酗酒男性和女性神经生理功能的一种新的敏感状态标记。这种反应主要发生在额叶脑区，与酗酒家族史无关，并受戒酒期的调节。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放电，从而解决酒精中毒已知的两个负面后果：大脑灰质的丧失和白质束的退化。重要的是，越来越多的证据表明，戒断后灰质和白质至少会部分恢复。因此，该应用建议评估受酒精滥用负面影响的神经机制，这也显示出戒断和睡眠δ活动（如K-复合物（KC））的恢复。该应用的独特之处在于对高分辨率脑结构、白质束微结构完整性和睡眠脑电图神经生理学测量的综合评估；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慢性酒精暴露后大脑系统退化和保留的模式，以及对戒酒后结构和功能恢复的评估。该建议有两个主要的具体目标：目标1：确定最近清醒的酗酒者和匹配对照中白质和灰质变化对诱发KC振幅的相对贡献。这些数据将允许评估白质微结构退化在酗酒者诱发δ脑电图振幅降低中的作用。目的2：确定酗酒者戒断相关的KC振幅恢复的时间过程，以及脑白质和灰质变化在恢复的脑电反应中的作用。要验证的假设是，随着时间的推移，戒酒者的大脑结构和功能完整性指数会有所恢复，而继续饮酒或复发的酗酒者的大脑结构和功能完整性指数会持续下降，而对照组的大脑结构和功能完整性指数几乎没有变化。这项创新研究将首次结合睡眠脑电图、结构MRI和弥散张量成像来评估酒精滥用导致大脑退化的机制；并通过节制来追踪大脑的恢复。这项工作将有助于建立戒断后大脑恢复能力的指标。

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.