Alcoholism, Sleep and the Brain

描述(申请人提供)：急性和长期饮酒导致睡眠障碍，这可能永远不会解决，并可能是酒精中毒复发的关键因素。随着年龄的增长，与酒精相关的睡眠缺陷也变得更加明显。最一致报道的酗酒者睡眠改变的发现是自发发生的慢波睡眠(SWS)减少，其定义是存在增量脑电活动。此外，基线SWS降低的酗酒者复发的可能性更大。 睡眠时的外部刺激可以引起K-复合体，当平均产生一个大的N550成分时，被认为具有与SWS Delta活动相同的生成器。考虑到睡眠标志物在预测复发方面的潜在价值，使用可以由实验人员控制的睡眠神经系统探测器将是有利的，而不是依赖于传统的自发睡眠生理指标观察。 我们已经证明，与年轻对照组相比，老年人睡眠诱发的N550成分的幅度更小，K-复合体的产生次数也更少。我们的初步研究表明，酗酒者的N550甚至比他们的年龄预期的要小。K-复合体和N550的候选生成器是额叶皮质灰质，在老年酗酒者中尤其减少。酒精中毒者和增龄者的脑结构和睡眠电生理指标也存在性别差异，对其进行客观研究有助于进一步了解酒精中毒性睡眠障碍的相关机制。我们建议检验以下假设： 假设1：与性别和年龄匹配的对照组相比，最近戒毒的慢性酗酒者的N550波幅更小，诱发的K-复合体比例更低，SWS水平和增量脑电功率更低。 假设2：低诱发K-复合体产生率、小N550波幅、低SWS水平和增量脑电功率将与额叶前部灰质体积小相关。 假设3：酗酒的男人比酗酒的女人有更大的睡眠障碍。 假设4：最近戒酒的人睡眠电生理变量的小幅度、产生率和功率将预测早期复发。

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.