Modulation of cortico-muscular coupling following electrical stimulation in chronic stroke subjects

Ph.D.Stroke is one of the leading causes of death and disability worldwide. Its survivors experience peripheral impairment contralateral to their stroke onset hemisphere, and more than half of them never achieved full motor recovery. Electrical stimulation might promote motor recovery by stimulating the brain or peripheral nerves. Transcranial direct current stimulation (tDCS) on the scalp could increase motor cortex excitability, while neuromuscular electrical stimulation (NMES) applied on the peripheral muscles could elicit sensory input and modulate the contralateral sensorimotor cortex. However, the modulatory mechanisms of electrical stimulation on stroke subjects are still not well understood. Cortico-muscular coupling is a neurophysiological indicator of functional coupling between brain and muscles, and might serve as a measure of cortical functional related contribution to motor recovery. This study explored cortico-muscular coupling following electrical stimulation using tDCS and NMES.Firstly, this work investigated whether high-definition (HD) tDCS could induce modulatory effects on the ipsilesional primary motor cortex in chronic stroke subjects. HD-tDCS has better stimulation focality and targeting ability, and can change motor excitability that significantly exceeds both the magnitude and duration of conventional tDCS. Each subject received three types of HD-tDCS (anode, cathode and sham) with at least one-week washout period. Wrist isometric contraction tasks were conducted for the affected upper limbs before and 10, 30, and 50 minutes after 10-minute 1mA HD-tDCS. The cortico-muscular coherence (CMC) was compared across task sessions and stimulation conditions. The largest neuromodulation effect was observed at around 10 min immediately after anode HD-tDCS, the effective modulation effects of HD-tDCS might not last more than 30 min for chronic stroke patients. Moreover, this work explored the bidirectional closed-loop motor control process and the direction of information flow following HD-tDCS, renormalized partial directed coherence (RPDC) based on multivariate autoregressive (MVAR) modeling was acquired. Anode HD-tDCS might only promote the descending pathways of cortico-muscular coupling, which demonstrates the functional role of the primary motor cortex to control the external muscles. The top-down neuromodulator might only influence the brain to muscle pathways in chronic stroke subjects.Moreover, the functional role of sensory-level NMES in neuro-motor control process during rhythmic pedaling was scrutinized. Both healthy and chronic stroke subjects participated in this study and underwent a ten-minute passive, active or NMES pedaling experiments. The neuromuscular contribution during different pedaling protocols was explored. The cortico-muscular coupling between identified cortical source clusters and lower limb muscles was calculated with generalized partial directed coherence (GPDC), GPDC of NMES pedaling was relatively similar to that of active pedaling, suggesting the facilitation effects of NMES in chronic stroke subjects. Sensory-level NMES could modulate the GPDC of both ascending and descending pathways for healthy subjects, but it could only induce significant modulation effects in ascending pathways for stroke subjects. Future studies could consider integrating NMES with other intervention techniques.In summary, this thesis expanded our understanding of human motor control following electrical stimulation. It also proved that electrical stimulation in the motor cortex and peripheral muscles could both modulate cortico-muscular coupling in stroke subjects. These findings implied that more effective stroke rehabilitation protocols based on electrical stimulation could be applied in clinical interventions.腦卒中又稱中風，是全球範圍內致死致殘的首要原因之一。腦卒中可導致腦損傷, 引起對側肢體運動障礙，半數以上患者無法完全恢復。電刺激可用於刺激大腦皮層或外周神經，進而促進患者運動功能康復。其中，經顱電刺激（tDCS）用於頭皮，可提高運動皮層的神經興奮性；神經肌肉電刺激（NMES）用於外周肌肉，誘發感覺輸入，並進一步調控對側感覺運動皮層。然而，電刺激對中風患者的調控機制尚不明確。神經肌肉耦合是一種用來描述大腦與肌肉間功能連接的方法，可用來表征運動康復過程中大腦機能。本文將重點研究中風患者電刺激條件下神經肌肉耦合機制的變化，研究範圍包括經顱電刺激和神經肌肉電刺激。首先，本文將高精度經顱直流電刺激（HD-tDCS）應用於慢性期中風病人患側初級運動皮層。HD-tDCS 有更好的刺激更集中更精確，相比傳統tDCS 可引起更明顯，持續時間更長的運動神經興奮。每位被試接受三種不同種類電刺激（陽極，陰極和偽刺激），刺激幅值1毫安，持續10 分鐘，刺激前、刺激后10，30，50 分鐘時間點進行患側腕關節等長收縮運動。通過分析運動過程中神經肌肉相干性（CMC）的改變，進而探索電刺激前後的神經調控機制。本文發現HD-tDCS可顯著改變病人神經肌肉耦合效應，最大調控效應發生在陽極電刺激結束后10 分鐘左右，且有效持續時間不超過30 分鐘。此外，基於多元自回歸模型(MVAR)，採用重整化偏定向相干性(PRDC) 方法，研究電刺激下神經肌肉耦合調控的方向性問題。研究表明陽極經顱電刺激只調控神經肌肉耦合的下行通路，這也說明了大腦運動皮層對外周肌肉的控制及自頂而下的神經調質只能影響中風病人的下行運動控制通路。此外，本文探索了感覺程度的神經肌肉電刺激（NMES）對恆速踩單車神經運動過程的影響。健康被試和腦卒中被試均參與了本實驗，實驗包括主動式、被動式以及NMES 單車運動。重點研究單車運動過程中神經肌肉的響應機制。採用廣義偏定向相干性（GPDC）方法研究運動過程中大腦源群與下肢肌肉間神經肌肉耦合效應。研究發現健康被試和腦卒中患者的神經肌肉耦合機制在神經肌肉電刺激場景下更接近於主動式踩單車而非被動式踩單車場景，這證明了神經肌肉電刺激對中風病人康復的促進作用。對健康被試，神經肌肉電刺激可同時調控上行及下行GPDC，而對中風被試，只能調控神經肌肉耦合的上行通路，可考慮將神經肌肉電刺激與其他干預措施結合使用。簡而言之，本研究拓展了對電刺激條件下人體運動控制策略的理解，證明了電刺激在大腦皮層或者外周肌肉都可以有效調控中風患者神經肌肉耦合效應，這有助於更好的基於電刺激進行中風康復治療。Bao, Shichun.Thesis Ph.D. Chinese University of Hong Kong 2019.Includes bibliographical references (leaves 159-180).Abstracts also in Chinese.Title from PDF title page (viewed on 16, December, 2020)