皮层－海马依赖的特异性脑电振荡在OSAHS学习记忆损伤中的机制探讨

Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a relatively common disorder frequently associated with neurocognitive impairment, which results in a significant impact on the patient’s quality of life. The underlying mechanisms of OSAHS-related learning and memory impairment remains largely unknown, however, the breath event-related arousal and sleep fragmentation is one of the mechanisms hypothesized to underlie the development of OSAHS-related neurocognitive impairment..There is emerging evidence suggesting that sleep can promote the memory consolidation, i.e., sleep and its disturbance alter the molecular signaling pathways within the hippocampal cortex networks and thalamocortical circuits that regulate synaptic plasticity, long-term potentiation and memory. The exemplary features of such neuronal dialogs are the sleep event-related brain oscillations, and these include slow, theta and spindle oscillations manifested as either the sleep-specific slow and/or spindle waves in the EEG. Recently, abnormal sleep event-related brain oscillations have been reported in OSAHS patients. Therefore, we hypothesize that the changes in hippocampal cortex-dependent brain oscillations play an important role in the development of OSAHS-related learning and memory impairment. .In this research proposal in the cohorts of consecutive OSAHS patients and matching control subjects using an integrated and interdiscipline approach with polysomnography and fMRI assessments, we aim to 1) characterize the profiles/changes of sleep-specific slow and spindle waves in EEG (Frontal, Central, Parietal & Occipital) in OSAHS patients; 2) observe the effect of REM sleep disturbance of cognition after reduce CPAP therapeutic only in REM sleep; and 3) determine the mechanism of hippocampal cortex-dependent brain oscillation in association with the various degrees of OSAHS-related learning and memory impairment.

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）导致患者学习记忆等认知领域的功能损伤，其危害重大而发生机制尚不明确，呼吸事件相关微觉醒、睡眠片断化已被证明是OSAHS认知损伤的重要原因。新近的系统巩固理论表明，睡眠调节皮层－丘脑、皮层－海马网络神经元之间的同步化活动，产生睡眠特异性脑电震荡（慢振荡、δ振荡和纺锤振荡），表现为脑电图上的慢波和睡眠纺锤波，进一步调节突触可塑性、促发长时程增强（LTP），影响记忆的形成与巩固。OSAHS睡眠特异性脑电震荡的异常，推测与学习记忆的损伤相关，且皮层下脑结构功能的异常可能是认知损害的内在因素。本课题采用睡眠微结构分析、循环交替模式分析以及磁共振特殊序列成像技术，观察OSAHS患者睡眠状态下大脑额区、中央区和枕区慢波、纺锤波的参数特征，同时观察REM期撤除CPAP作用后的变化，与其学习记忆能力间的相关性，探讨睡眠微结构改变在OSAHS学习记忆损害中的机制。

目的：阻塞性睡眠呼吸暂停低通气综合征（OSAHS）导致以学习记忆为中心的认知功能损伤，其发病机制不明，治疗手段缺乏，本项目旨在探寻OSAHS学习记忆损伤的可能机制。.方法：纳入符合入排条件的OSAHS患者约200余例，行学习记忆、注意、执行等认知评估、多导睡眠监测、经皮二氧化碳水平监测，以及颅脑磁共振扫描、颅脑彩超检查；进行脑电功率谱、循环交替模式分析（CAP）、纺锤震荡等脑电微结构分析，以及基于SBM、VBM的脑结构MR序列分析等，评估不同脑区脑电微结构改变、脑电功率谱变化、以及颅脑结构、脑血流变异度、及二氧化碳水平与学习记忆等认知功能的相关性；通过对CPAP治疗后的患者在REM期急性撤机，观察撤机前后REM睡眠的变化及其与认知功能改变的相关性。.结果：1）建立了量表联合CANTAB软件的认知功能评估体系，结果发现OSAHS患者在数字、图形、语言、空间工作记忆上的损伤，以及注意和视觉空间执行功能的损害；2）脑电循环交替模式（CAP）分析表明，OSAHS睡眠微结构的不稳定性增加，CAP循环数、A3指数增加，增加的A3指数与认知功能呈反比；3）脑电功率谱分析显示，OSAHS患者额叶、中央和枕部代表脑电慢化，表现为delta功率谱密度增高、delta/alpha升高，增高的delta功率谱与PSG参数相关，经CPAP治疗后，脑电慢波化呈部分逆转现象；纺锤波密度分析显示，重度OSAHS患者纺锤波密度下降；4）头颅MRI和脑超影像学结果显示，间歇性缺氧和睡眠碎片化导致OSAHS大脑皮质复杂度下降和脑血流变异度下降；6）REM期急性降压后，患者在REM睡眠期的呼吸事件及睡眠紊乱程度增加，降压前后认知功能存在差异，REM期相关OSAHS存在学习记忆能力下降；7）OSAHS患者存在日间高碳酸血症及，且高碳酸血症组患者认知功能较非高碳酸血症组显著下降。.结论： OSAHS患者存在学习记忆等广泛的认知领域损伤，其睡眠微结构改变、高碳酸血症，导致特异性脑电震荡异常、脑电频谱慢化，以及颅脑结构和功能改变是OSAHS学习记忆损伤的可能机制。