深部脑刺激改善帕金森病运动障碍的脑网络机制研究

Parkinson’s disease (PD) is a common neurodegenerative disorder with motor dysfunction. Deep brain stimulation (DBS) is an effective treatment in alleviating the PD motor dysfunction. The research makes a hypothesis that there is a dysfunctional network connectivity between subthalamic nucleus (STN) and primary motor cortex (M1), resulting in the occurrence of motor symptoms in PD. Research purpose: This project is to address the question that how the therapeutic effect of STN-DBS contributes to the abnormal M1 functional connectivity which, in turn, improves the motor dysfunction. Research contents: (1) Preparation and identification of PD rats. (2) Rats are divided into four groups: Control group, Control + STN-DBS group, PD group and PD + STN-DBS group. (3) While rats are performing in the open field test, behavioral data are measured before, during and after STN-DBS. At the same time, LFPs in M1 and STN are recorded using a multi-channel electrophysiological data acquisition system. The characteristic frequency band of LFPs is extracted using spectral analysis. (4) The global properties in LFP network are computed via spectral Granger causality analysis. (5) The abnormal M1 network in PD is studied by using a combination o f the behavioral results and LFP network characteristics. (6) The hypothesis of PD pathogenic STN-M1 network is verified: there are significant differences on STN-M1 network connectivity between PD and control group. Further, the therapeutic effect of STN-DBS treats PD motor symptoms through regulating abnormal M1 network is researched. Research significance: The project is expected to provide insight for the underlying mechanism research behind motor dysfunction in PD and the clinical application of STN-DBS in PD.

帕金森病（PD）是一种神经退行性疾病，深部脑刺激（DBS）是改善PD运动障碍的神经调控技术。本项目提出PD致病网络假设：底丘脑核（STN）和初级运动皮层（M1）存在异常网络连接。研究目的：研究STN-DBS通过调控M1改善PD运动障碍的脑网络机制。研究内容：（1）制备和认定PD大鼠；（2）分组：正常、正常+DBS、PD、PD+DBS；（3）记录大鼠在DBS前、中和后的旷场行为学，应用双脑区植入微电极阵列技术记录M1和STN多通道局部场电位（LFPs），提取特征频段；（4）应用频域因果分析描述网络连接特性；（5）结合行为学和M1网络特征，研究PD运动障碍M1网络异常特性；（6）验证PD运动障碍STN-M1致病网络假说：PD组和正常组STN-M1网络连接存在显著性差别，进一步研究STN-DBS通过调控M1网络改善PD运动障碍的机制。研究意义：为DBS改善PD运动障碍机制研究和临床应用提供支持。

帕金森病（Parkinson’s disease, PD）是仅次于阿尔茨海默病的第二位最常见中枢神经系统变性疾病。由于PD运动障碍的确切病因十分复杂，因此对其发病机制及有效治疗方案的研究是全球学者致力探究的重大医学命题。深部脑刺激（deep brain stimulation, DBS）作为一项神经外科手段已被应用于PD运动障碍治疗，而底丘脑核（subthalamic nucleus, STN）是被认可的DBS治疗靶点。本项目旨在研究PD运动障碍的异常脑网络机制，以及STN-DBS改善运动障碍的作用机制。.基于本项目的科学问题：STN-DBS对PD运动症状的改善作用并非单纯作用于STN本身，而是通过调控运动皮层的电活动产生治疗效应，项目团队应用在体多通道微电极植入技术采集初级运动皮层（primary motor cortex, M1）的局部场电位（local field potentials, LFPs），同时记录大鼠的行为学，通过分析LFP信号的电生理特性，结果发现，与正常大鼠相比，PD大鼠出现自发性探索行为障碍，同步记录到的M1区LFP信号的beta振荡能量显著增高，16通道LFPs之间网络全局效率异常增强，表明PD大鼠模型在运动状态下M1区存在异常的网络连接特性。进一步地，对PD大鼠模型进行STN-DBS治疗，结果发现，PD大鼠的运动障碍得到了改善，相应地，异常增强的M1区网络全局效率也得到了抑制，证实STN-DBS是通过影响M1网络特性进而改善运动障碍。此外，本研究团队还对实验所用DBS刺激电极作了改进，使得对不规则脑区STN的定位更加准确，为未来继续开展PD治疗机制的研究打下坚实基础。.本项目表明PD运动障碍的发生与特定脑区神经信息网络的异常连接紧密相关，可为临床检测和评估PD的发生和评价PD的治疗效果提供有效的技术支持，具有重要的学术意义和临床应用价值。