Alcoholism, Sleep and the Brain

酗酒、睡眠和大脑

• 批准号: 7067533
• 负责人: Ian Michael Colrain
• 金额: $ 48.49万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067533
• 关键词: alcoholism /alcohol abuse; biomarker; brain electrical activity; clinical research; detoxification; drug /alcohol abstinence; electrophysiology; gender difference; human subject; magnetic resonance imaging; polysomnography; relapse /recurrence; sleep

DESCRIPTION (provided by applicant): Acute and chronic alcohol consumption causes sleep disturbances, which may never resolve and may be a key factor in alcoholism relapse. Alcohol-related sleep deficits also become more pronounced with advancing age. The most consistently reported finding of altered sleep in alcoholics is a reduction in spontaneously occurring slow wave sleep (SWS), defined by the presence of delta EEG activity. Further, alcoholics with reduced baseline SWS have an increased likelihood of relapse. External stimulation during sleep can elicit K-complexes, which when averaged produce a large N550 component thought to have the same generator as SWS delta activity. Given the potential value of sleep markers in predicting relapse, it would be advantageous to employ a probe of the sleeping nervous system that can be under experimenter control rather than one that relies on the traditional observation of spontaneous sleep physiological indices. We have demonstrated that sleep-evoked N550 component amplitudes are smaller and K-complexes are produced on a smaller number of trials in elderly than young controls. Our preliminary study indicates that alcoholics have even smaller N550 than would be expected for their age. A candidate generator of the K-complex and N550 is frontal cortical gray matter, which is especially reduced in older alcoholics. Sex differences in brain structure and electrophysiological indices of sleep also occur in alcoholism and aging, and objective study of them may further contribute to our understanding of relevant mechanisms of alcoholism-related sleep disturbance. We propose to test the following hypotheses: Hypothesis 1: Recently detoxified, chronic alcoholics will have smaller N550 amplitudes, lower evoked K-complex proportions, lower SWS levels and delta EEG power compared to sex- and age-matched controls. Hypothesis 2: Low evoked K-complex production rates, small N550 amplitude, low SWS levels and delta EEG power will be associated with small prefrontal gray matter volume. Hypothesis 3: Alcoholic men will have greater sleep abnormalities than alcoholic women. Hypothesis 4: Small amplitude, production rate and power of sleep electrophysiological variables in recently detoxified alcoholics will predict early relapse.

描述（由申请人提供）：急性和慢性酒精消耗会引起睡眠障碍，这可能永远无法解决，可能是酒精中毒复发的关键因素。随着年龄的增长，与酒精有关的睡眠不足也变得更加明显。据报道，酗酒者睡眠改变的发现最为始终如一的发现是自发发生的慢波睡眠（SWS）的减少，这是由三角洲EEG活性的存在所定义的。此外，基线SW的酗酒者的复发可能性增加。 睡眠期间的外部刺激会引起k复合物，当平均产生大型N550组件时，被认为具有与SWS Delta活动相同的发电机。鉴于睡眠标志物在预测复发中的潜在价值，使用可以在实验者控制下进行睡眠神经系统的探测，而不是依赖于自发睡眠生理指数的传统观察，这将是有利的。 我们已经证明，睡眠诱发的N550组件振幅较小，并且在老年人的试验中比Young对照组生产K复合物。我们的初步研究表明，酗酒者的N550甚至比其年龄所预期的要小。 K-Complex和N550的候选发电机是额叶皮质灰质，在老年酗酒者中尤其降低。酒精中毒和衰老的睡眠中，大脑结构和电生理学指标的性别差异也可能进一步有助于我们对酒精中毒相关睡眠障碍的相关机制的理解。我们建议检验以下假设： 假设1：与性别和年龄匹配的对照相比，最近排毒的慢性酗酒者将具有较小的N550幅度，较低的K-复合物比例，较低的SWS水平和Delta EEG功率。 假设2：低诱发的K复合物的生产率，小N550振幅，低的SWS水平和Delta EEG功率将与较小的前额叶灰质体积相关。 假设3：酗酒男性的睡眠异常比酒精妇女更大。 假设4：在最近排毒的酒精中毒中，睡眠电生理变量的小幅度，生产率和功率将预测早期复发。