臺灣博碩士論文加值系統

高頻θ脈衝式經顱磁刺激 (TBS) 可以有效地調節皮質的興奮性和引起類似長期增益或抑制的神經可塑性。然而能否改變中風後的恢復仍屬未知。我們的目標是研究施予延長型的TBS (每次1200 脈衝) 在健康者的主要運動皮質區 (M1) 所引發的皮質調節，以及評估在亞急性中風患者的梗塞側M1 施予間歇性TBS (iTBS)的效果，利用多重方法包括上肢功能、電生理運動誘發電位 (MEPs)、以及提舉手指的相關腦磁圖等。十位健康受試者施予單次iTBS 後，源自刺激側 M1 的MEPs 以及動作後beta 同步律動腦波的能量顯著增加，而源自非刺激側 M1 的兩者則是減少，暗示不止刺激側被興奮還有跨腦側的抑制效應。進一步，九位首次、單側、中大腦動脈區的缺血性中風患者 (中風後二至四週內)、合併嚴重手部癱瘓，依隨機分派為兩組分別在損傷側 M1 施予十次 iTBS 或偽刺激 (每日一次)，並同時接受標準的藥物與復健治療。在中風後六十日，實驗組的癱瘓上肢相較於對照組有明顯的功能進步 (Action Research Arm test and Fugl-Meyer test)。所有的受試者沒有發生嚴重的副作用。我們的結果首次驗證 iTBS 是安全、且可能引發長期的神經重塑來促進中風病人的恢復，其機制可能是透過活化皮質內的代償徑路以及抑制對側同源神經網絡的活動。

Theta burst stimulation (TBS) can efficiently modulate ortical excitability and elicit long-term potentiation/depression-like plasticity. However, it remains unexplored how TBS may affect post-stroke plasticity and recovery. We aim to investigate the cortical modulation by a prolonged protocol of TBS (1200 pulses per session) over the primary motor cortex (M1) in healthy subjects, and evaluate therapeutic application of intermittent TBS (iTBS) over the ipsilesional M1 in subacute stroke patients by multi-modality assessments, including functional tasks, motor evoked potentials (MEPs), and magnetoencephalography (MEG) during self-paced finger lifting. The amplitude of MEPs and post-movement beta synchronization were significantly enhanced by iTBS at the stimulated M1, but suppressed at the non-stimulated M1 in ten healthy subjects, suggesting intrahemispheric facilitation as well as interhemispheric inhibition. Moreover, nine patients with first-ever, monohemispheric ischemic stroke for 2-4 weeks, and severe paretic hand were randomized to receive ten daily sessions of either iTBS or sham stimulation in addition to standardized medical and rehabilitation treatments. The patients receiving iTBS, as compared to the controls, had markedly improved Action Research Arm test and Fugl-Meyer test scores on the 60th day post-stroke from baseline. No serious adverse effects were observed. The results provide the first evidence that iTBS may induce safe and long-term plasticity for post- troke recovery, probably through intracortical activation of compensatory sprouting and interhemispheric inhibition of the contralateral homologous circuits.

CHINESE ABSTRACT......................................... I
ENGLISH ABSTRACT ....................................... II
LIST OF ABBREVIATIONS ................................. III
TABLE OF CONTENTS ...................................... IV
LIST OF TABLES AND FIGURES...............................VI
INTRODUCTION ............................................ 1
Post-stroke plasticity .................................1
Brain stimulation strategy in stroke patients ......... 1
Theta burst stimulation and underlying mechanisms ..... 2
Magnetoencephalography for movement-related cortical
oscillations .......................................... 3
Application of TBS in stroke patients ................. 3
AIMS .................................................... 4
MATERIAL AND METHODS .................................... 5
Subjects .............................................. 5
Study design .......................................... 6
Theta burst stimulation paradigms ..................... 7
Motor functional tests ................................ 8
Measurement of corticospinal excitability ............. 8
MEG ................................................... 8
Extraction of sensorimotor oscillations............... 10
Quantification of movement-related desynchronization/
synchronization ...................................... 11
Statistical analysis......................... .........12
RESULTS ................................................ 13
Effects of TBS1200 in healthy volunteers ............. 13
Spatial sensorimotor oscillations from MEG in healthy
subjects ..............................................14
Sources of sensorimotor oscillations in healthy
subjects...............................................14
Intermittent TBS enhanced beta synchronization in healthy
subjects.............................................. 15
Enrollment of subacute stroke patients ................15
Intermittent TBS improved motor recovery in stroke
patients ............................................. 16
Functional recovery in stroke patients ............... 16
Electrophysiological evaluation in stroke patients ... 16
Sensorimotor oscillations after iTBS and during stroke
recovery.............................................. 17
DISCUSSION ............................................. 18
Physiological basis of intermittent TBS .............. 18
Intermittent TBS modulated beta synchronization and
intracortical circuits ............................... 21
Therapeutic effects of intermittent TBS in subacute
stroke patients ...................................... 22
CONCLUSIONS ............................................ 23
ACKNOWLEDGEMENT ........................................ 25
REFERENCES.............................................. 26
APPENDIX................................................ 45

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