Alcoholism, Sleep and the Brain

描述（由申请人提供）：急性和慢性饮酒导致睡眠障碍，这可能永远不会解决，可能是酗酒复发的关键因素。与酒精相关的睡眠不足也随着年龄的增长而变得更加明显。酗酒者睡眠改变的最一致报道是自发发生的慢波睡眠（SWS）减少，定义为δ EEG活动的存在。此外，基线SWS降低的酗酒者复发的可能性增加。 睡眠期间的外部刺激可以引起K复合物，当平均时产生大的N550组分，其被认为具有与SWS δ活动相同的发生器。考虑到睡眠标记物在预测复发中的潜在价值，采用可以在实验者控制下的睡眠神经系统的探针而不是依赖于自发睡眠生理指标的传统观察的探针将是有利的。 我们已经证明，睡眠诱发的N550成分的振幅较小，K-复合物产生的试验在老年人比年轻的控制数量较少。我们的初步研究表明，酗酒者的N550甚至比他们这个年龄的预期还要小。K复合体和N550的候选生成器是额叶皮质灰质，这在老年酗酒者中尤其减少。酒精中毒和衰老也存在脑结构和睡眠电生理指标的性别差异，对其进行客观研究有助于我们进一步了解酒精中毒相关睡眠障碍的相关机制。我们建议检验以下假设： 假设1：最近脱毒，慢性酗酒者将有较小的N550振幅，较低的诱发K复合体的比例，较低的SWS水平和δ EEG功率相比，性别和年龄匹配的控制。 假设二：低诱发K复合波产生率、小N550振幅、低SWS水平和δ EEG功率将与小的前额叶灰质体积相关。 假设3：酗酒的男性比酗酒的女性有更大的睡眠异常。 假设4：小振幅，生产率和功率的睡眠电生理变量在最近脱毒酗酒者将预测早期复发。

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.