脑深部电刺激对帕金森病运动环路振荡干预机制的研究

Parkinson’s disease（PD）is one of the most prevalent neurodegenarative disease, which causes a serious health burden in the middle and old age population. Deep brain stimulation (DBS) alleviates the motor sympotoms of PD patients s such as rigidity，akinesia and tremor efficiently, but the mechanism is not clear. It is well recognized that DBS suppresses or over-rides pathologically synchronised oscillatory activity including α wave (8-12 Hz) and β wave (13-35 Hz) in motor curcuit. In our previous study, the correlations between the suppression of α and β wave over temporal, pariental regions and improvement of motor functions were discovered with detection of magnetoencephalography(MEG), and the gamma wave (30-90 Hz) increased with the treatment of DBS to STN. Recently, it's reported that gap junction protein expression increases in the basal ganglia of Parkinson's disease patients, and the overexpression is involved in the oversynchronizaiton in basal ganglia. In this project, we are going to record the local field potential (LFP) of STN with the implanted stimulating electrodes and cortical magnetic field simultaneously with MEG in PD patients to discover the coherence of the oscillation inside the basal ganglia-motor cortex circuit in PD patients. Additionally, the 6-OHDA leisioned PD rat models will be generated, and be implanted stimulating electrodes and recording electrodes latelly, to explore the association of gap junction to the oversynchronization in basal ganlia of PD, and the influence of the treatment of DBS to STN on gap junction. The results of this project will discover the mechanism of DBS to PD, and provide new ideas and evidences to the neuromodulation to PD.

脑深部电刺激有效改善帕金森病患者的僵直、运动不能和震颤等症状，但治疗机制并不清楚。目前研究显示，高频电刺激抑制运动环路alpha和beta波（8-35 Hz）过度同步化；本课题组研究发现，脑深部电刺激对帕金森病患者运动功能改善与抑制大脑皮层alpha和beta波相关，并且增加体感运动区的gamma波(30-90 Hz)的活动。另外，有研究者发现，帕金森病基底节缝隙连接过度表达，可能与过度同步化有关。因此，本项目中，为探索脑深部电刺激对皮层基底节运动环路振荡的干预及机制，在帕金森病患者安静和做握拳运动时，同时记录脑磁图、丘脑底核的局部场电位和肌电图，分析脑网络功能变化；另外，构建帕金森病大鼠模型，研究缝隙连接与运动环路过度同步化的关系，以及脑深部电刺激对运动环路同步化的影响与缝隙连接的关系。本课题的顺利进行，将揭示脑深部电刺激治疗帕金森病的机制，并且为神经调控治疗提供新思路和新方法。

帕金森病患者以肌张力增高和运动不能为主要症状，有的患者还伴有有震颤。美多巴和脑深部电刺激有效改善帕金森病患者的症状，但是对大脑运动环路振荡的影响并不清楚。目前已有研究通过植入到刺激靶点的刺激电极，记录靶点的局部场电位（Local field potential, LFP)，发现丘脑底核alpha和beta波（8-35 Hz）过度同步化，高频电刺激抑制核团过度同步化。.高频电刺激和服用美多巴对基底节核团过度同步化的抑制与症状的改善相关。但是帕金森病的治疗对运动环路的整体影响并不清楚。本研究通过脑磁图记录研究脑深部电刺激和美多巴药物治疗对皮层的影响。并且通过同步记录脑磁图和LFP，研究皮层和皮层下基底节核团在进行go no go任务时的反应。从而探索运动过程中皮层和皮层下结构间的协同过程。本研究发现，脑深部电刺激抑制皮层alpha波的活动，美多巴药物治疗增加运动皮层beta波的活动，从而推断脑深部电刺激和美多巴治疗对皮层震荡的影响不同。美多巴减少顶叶beta波位相延迟指数，这可能与增加运动区的beta活动有关。另外，我们还研究脑深部电刺激对帕金森病患者大脑葡萄糖代谢率的影响，发现脑深部电刺激明显增加运动区葡萄糖代谢率。为深入了解基底节起源的运动障碍病的运动环路特点，以及在决策执行时的反应，我们同时入主帕金森病和肌张力障碍患者，在记录脑磁图和基底节场电位的同时，患者进行go no go任务测试，目前数据正在分析总结中。