Sleep EEG and MRI Markers of Brain Recovery with Alcohol Abstinence

描述(申请人提供)：头皮记录睡眠中的脑电增量活动是稳态调节的，在维持神经和身体健康方面具有重要作用。低水平的Delta值活动是酗酒者普遍存在的睡眠障碍的一部分。睡眠增量活动不足已被证明可以预测复发，这是因为在恢复饮酒后感觉到睡眠改善而导致饮酒增加。我们先前发现睡眠中诱发的脑电频率反应是反映酗酒男女神经生理功能的一种新的、敏感的状态标记物。这些反应主要集中在前额脑区域，看起来与酗酒家族史无关，并受到戒酒时期的调节。高幅度脑电反应的产生需要大量健康神经元的高度同步放电，从而解决了酒精中毒已知负面后果的两个方面：大脑灰质丢失和白质束退化。重要的是，越来越多的证据表明，在戒酒的情况下，灰质和白质都可能至少部分恢复。因此，这一应用程序建议评估酒精滥用带来的负面影响的神经机制，这些机制也显示出戒酒后的恢复和睡眠三角洲活动的基础，如K-复合体(KC)。这一应用的独特之处在于对高分辨率大脑结构、白质束微结构完整性以及睡眠脑电测量神经生理学的综合评估；所有这些都使用了安全和非侵入性技术。这些数据将使我们能够评估长期饮酒后大脑系统的退化和节制模式，以及在戒酒后结构和功能恢复的评估。该提案有两个主要的具体目标：目标1：确定白质和灰质变化对最近戒酒的酒精者和匹配的对照组诱发的KC波幅的相对贡献。这些数据将有助于评估白质微结构退化在酗酒者诱发的增量脑电幅度降低中的作用。目的：探讨酒精依赖诱发的KC波幅在戒断后恢复的时程以及脑白质和灰质改变在恢复的脑电反应中的作用。需要检验的假设是，戒酒者的大脑结构和功能完整性指数将随着时间的推移而恢复，而继续饮酒或复发的酗酒者将表现出持续的下降，而对照组将几乎没有变化。这项拟议的创新研究将首次将睡眠脑电、结构磁共振和扩散张量成像结合起来，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。这项工作将有助于建立禁欲情况下大脑恢复能力的衡量标准。

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.