快眼动睡眠期行为障碍（RBD）运动事件启动机制的PSG研究

Rapid-eye-movement (REM) sleep behavior disorder (RBD) is a common sleep disorder often seen in Parkinson's disease, it exhibits dream-enacted behaviors (DEB) that expose the patients and bed partners to a high risk of injury and sleep disruption. The neural mechanisms of RBD, however, are not fully understood. RBD overt phenotypes include REM sleep without atonia (RSWA), simple behaviors and complex dream associated behaviors. RBD is currently thought due to neuropathology in the upper pons. However, it is not known how the pons is involved in dreaming and DEB. As we have observed that RBD subjects have high cortical excitability, and we thus hypothesize that the cortex is involved in EBD of RBD while brainstem is involved in generation of simple behaviors of RBD. Our current grant application intends to classify REM sleep period with RSWA, simple and complex behaviors of RBD by polysomnography recording (PGS), power spectrum and Hall Van de Castle system are then be used to evaluate cortex excitatory among these different condition. In addition, we will particularly focus on RBD cases of Parkinson's disease and clonazeoam treatment that show less or no DEB. Finally, we will create RBD in animals by lesioning the sub-laterodosal tegmental nucleus (SLD) and further ask and test whether lesions of motor cortex can eliminate complex behaviors. Our data from this grant will help to elucidate the causes of RBD and provide new potential treatments for RBD.

快眼动睡眠期行为障碍（RBD）是常见的睡眠疾病，患者在REM期出现险恶梦境和异常行为，对自身及同床者造成伤害，其产生机制未明。RBD的运动表现分为肌电失弛缓（RSWA）和梦境演绎行为（DEB）。目前认为与脑干核团损害有关。但脑干结构无法解释梦境改变和复杂的行为活动。我们观察到RBD患者皮层兴奋性增高，因此提出皮层兴奋参与DEB的启动，脑干核团参与RSWA形成的假说。本申请拟采用PSG技术区分有/无DEB的REM期，以脑电波谱分析及Hall-Van-de-Castle梦境分级法评价两种情况下皮层活跃度的差异。同时，对PD起病后及Clonazepam治疗后DEB消失的患者进行评估，来验证DEB/RSWA涉及不同神经结构的观点。另外，使用脑桥背外侧下核损害的RBD大鼠模型，在抑制运动皮层后观察RSWA残留情况，从动物水平验证假说。预期结果将有助于阐明RBD的起病机制，为防治措施提供新靶点。

特发性快眼动睡眠期行为障碍（iRBD）以REM睡眠期肌肉失弛缓，患者出现不同严重程度的肌电图异常和/或异常行为为主要特征。一般认为其发生机制与脑干核团损伤有关，但脑干结构异常无法解释RBD患者梦境改变和梦中出现的复杂行为活动。本研究的目的在于证实大脑大脑皮层及皮层下结构亦参与RBD的形成。本研究对21例iRBD患者进行18氟-FDG-PET显像，发现iRBD患者存在特有的脑葡萄糖代谢模式（RBDPR）。其特征表现为丘脑、中央前回、辅助运动区、海马、缘上回，脑桥和小脑后部代谢增高,而枕叶和中脑代谢减低。21例iRBD患者在氯硝西泮治疗前后接受了两次PSG检查。分析显示：氯硝西泮干预后，iRBD患者REM睡眠期时相性肌电活动指数较基线明显降低（下颌肌电 P<0.05，下肢肌电P<0.01）。紧张性肌电活动指数虽有降低，但未达到统计学意义。反映POG波的快眼动指数无明显变化。脑电波谱分析显示，氯硝西泮治疗后双侧中央区α及θ波段脑电波谱值降低（P<0.05）。动物实验部分：在1-10%间尝试不同浓度鹅膏蕈氨酸注射大鼠SLD，以5%鹅膏蕈氨酸成模率和成活率可达平衡。成模大鼠表现出良好的肌电失弛缓现象，同时出现典型的RBD行为学表现。但安定注射后死亡率增加，未能获得治疗组和非治疗组脑电波普分析结果。总之，我们的研究提示，RBD患者的幕上结构亦出现功能改变，形成特有的代谢模式，参与疾病的形成。