Investigating deep brain stimulation-induced plasticity in Parkinson’s disease by concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG)

植入基底节（BG）的脑深部电刺激（DBS）可改善帕金森病（PD）患者的运动症状。然而，DBS的神经生理机制尚未完全了解。鉴于BG中的活动影响其他脑区（如运动皮层）的活动以影响运动，研究DBS对BG-皮层关系影响的因果机制非常重要。经颅磁刺激（TMS）与脑电图（EEG）相结合，允许直接调查大脑皮层的兴奋性，功能连接和动态振荡功能的可塑性为基础的干预前后。虽然经典的TMS-EMG研究仅限于初级运动皮层的研究，并且唯一的读出是从手部肌肉记录的运动诱发电位（MEP），但TMS-EEG由于其高时间分辨率而允许跨多个时空和频谱尺度调查运动和非运动区域。这些优点导致建立特定的TMS-脑电图标记在健康和疾病，用于研究大脑疾病的病理生理学。TMS-EEG标记还可用于指导治疗或预测治疗结果。经颅磁刺激诱发一系列的正、负偏转，这些偏转是兴奋性和抑制性突触后电位的时间和空间叠加;这些经颅磁刺激诱发的脑电电位（TEPs）根据其极性和潜伏期进行标记，具有高度的可重复性。以往的研究表明运动区TEPs的早成分（<30 ms）是皮质脊髓和皮质皮层系统兴奋的标志，而运动区TEPs的负成分（N45和N100）与抑制机制有关。本项目将利用这些TEP标记来研究单脉冲TMS-EEG对年龄匹配的健康受试者和PD患者在DBS关闭与打开状态下的辅助运动区（SMA），初级运动皮层（M1）和后顶叶皮层（PPC）的影响，以提供对PD中改变的皮层状态的新见解。我还将使用TMS-EEG方法来研究最近开发的协议的电生理机制和疗效，该协议在特定时间将DBS与重复运动皮层TMS配对，以调节PD患者的皮层可塑性。通过定义三个目标皮层区域的病理性振荡特征，本研究将提供对PD以及DBS如何改变PD病理生理学的更好理解。

Deep brain stimulation (DBS) implanted in the basal ganglia (BG) can improve motor symptoms in patients with Parkinson’s disease (PD). However, the neurophysiological mechanisms underlying DBS is not fully understood. Given that the activities in the BG influence activities in other brain areas such as the motor cortex to affect movement, studying the causal mechanisms governing the effects of DBS on the BG-Cortical relationship is of great importance. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows direct investigation of cortical excitability, functional connectivity and dynamic oscillatory features of human brains before and after plasticity-based interventions. While classical TMS-EMG studies are limited to the studies of the primary motor cortex and the only readout is motor evoked potentials (MEPs) recorded from a hand muscle, TMS-EEG allows investigating of both motor and non-motor regions across multiple spatiotemporal and spectral scales due to its high temporal resolution. These advantages lead to the establishment of specific TMS-EEG markers in health and disease which are used to study the pathophysiology of brain disorders. TMS-EEG markers can also be utilized to guide treatments or to predict therapeutic outcomes. TMS evokes a sequence of positive and negative deflections which are the temporal and spatial summation of excitatory and inhibitory postsynaptic potentials; these TMS-evoked EEG potentials (TEPs) which are labeled according to their polarity and latency are highly reproducible. Previous studies showed that early component (<30ms) of TEPs of the motor area is a marker of excitation of the corticospinal and corticocortical system, while negative TEP components of motor areas (N45 and N100) have been associated with inhibitory mechanisms. The present project will take advantage of these TEP markers to investigate the effects of a single-pulse TMS-EEG to the supplementary motor area (SMA), the primary motor cortex (M1) and the posterior parietal cortex (PPC) in age-matched healthy subjects and in PD patients in DBS switch off vs. on state to provide new insights on the altered cortical state in PD. I will also use TMS-EEG methodology to study the electrophysiological mechanisms and efficacy of a recently developed protocol, which pairs DBS with repetitive motor cortical TMS at specific times, in modulating cortical plasticity in PD patients. By defining the pathological oscillatory signatures of the three targeted cortical areas, this study will provide a greater understanding of PD and how DBS changes PD pathophysiology.