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: 8308351
• 负责人: Ian Michael Colrain
• 金额: $ 22.03万
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308351
• 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.

描述（由申请人提供）：睡眠期间头皮记录的脑电图 delta 活动受到稳态调节，在维持神经和身体健康方面具有重要作用。低水平的δ活性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，因为恢复饮酒后感知到的睡眠改善会导致饮酒强化。我们之前已经将睡眠期间诱发的脑电图δ频率响应确定为酗酒男性和女性神经生理功能的一种新颖且敏感的状态标记。这些反应主要集中在额叶大脑区域，似乎与酗酒家族史无关，并且受到禁欲期的调节。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，从而解决已知的酗酒负面后果的两个方面：大脑中灰质的损失和白质束的退化。重要的是，越来越多的证据表明，灰质和白质在禁欲后可能至少会部分恢复。因此，本申请建议评估受酒精滥用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，例如 K-复合物 (KC)。该应用的独特之处在于对高分辨率大脑结构、白质束微观结构完整性以及神经生理学睡眠脑电图测量的综合评估；全部使用安全和非侵入性技术。这些数据将允许评估长期饮酒后大脑系统的退化和保留模式，以及评估戒酒后的结构和功能恢复。该提案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的δ脑电图振幅降低中的作用。 目标 2：确定戒酒相关的酗酒者诱发 KC 振幅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。待测试的假设是，随着时间的推移，戒酒者的大脑结构和功能完整性指数将出现恢复，而继续饮酒或复发的酗酒者将表现出持续下降，而对照组则几乎没有变化。拟议的创新研究将是第一个结合睡眠脑​​电图、结构磁共振成像和扩散张量成像来评估酗酒引起的大脑退化机制的研究；并通过禁欲来追踪大脑的恢复情况。这项工作将有助于建立禁欲后大脑恢复能力的指标。

项目成果

Evoked K-complexes and altered interaction between the central and autonomic nervous systems during sleep in alcohol use disorder.

• DOI: 10.1016/j.alcohol.2019.09.005
• 发表时间: 2020-05
• 期刊: ALCOHOL
• 影响因子: 2.3
• 作者: Willoughby, Adrian R.;de Zambotti, Massimiliano;Baker, Fiona C.;Colrain, Ian M.
• 通讯作者: Colrain, Ian M.

Partial K-Complex Recovery Following Short-Term Abstinence in Individuals with Alcohol Use Disorder.

• DOI: 10.1111/acer.12769
• 发表时间: 2015-08
• 期刊: Alcoholism, clinical and experimental research
• 作者: Willoughby AR;de Zambotti M;Baker FC;Colrain IM
• 通讯作者: Colrain IM

Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence.

• DOI: 10.1016/j.alcohol.2014.07.023
• 发表时间: 2015-06
• 期刊: ALCOHOL
• 影响因子: 2.3
• 作者: de Zambotti, Massimiliano;Willoughby, Adrian R.;Baker, Fiona C.;Sugarbaker, David S.;Colrain, Ian M.
• 通讯作者: Colrain, Ian M.

Poor autonomic nervous system functioning during sleep in recently detoxified alcohol-dependent men and women.

• DOI: 10.1111/acer.12384
• 发表时间: 2014-05
• 期刊: Alcoholism, clinical and experimental research
• 作者: de Zambotti M;Baker FC;Sugarbaker DS;Nicholas CL;Trinder J;Colrain IM
• 通讯作者: Colrain IM