Examining the Impact of Transcranial Magnetic Stimulation Intensity on Instantaneous Brain Communication with Dynamical EEG Analysis

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题名:	Examining the Impact of Transcranial Magnetic Stimulation Intensity on Instantaneous Brain Communication with Dynamical EEG Analysis
作者:	周立安;Chou, Li-An
贡献者:	認知與神經科學研究所
关键词:	經顱磁刺激-腦電圖;肌電圖;經顱磁刺激誘發電位;腦波相位振幅耦合;TMS-EEG;Electromyogram;TMS-Evoked Potentials;Holo-Hilbert cross-frequency phase clustering
日期:	2025-07-08
上传时间:	2025-10-17 12:46:29 (UTC+8)
出版者:	國立中央大學
摘要:	經顱磁刺激（Transcranial Magnetic Stimulation, TMS）技術已廣泛應用於神經科學領域，藉由非侵入性操作探討大腦皮質興奮性及神經網絡動態。本研究採用TMS與腦電圖（Electroencephalography, EEG）同步記錄技術，系統性探討不同刺激強度以及眼睛狀態（睜眼與閉眼）對大腦皮質興奮性及對功能性連結的影響。實驗中，針對左側初級運動皮質（Primary Motor Cortex, M1），根據各受試者靜息動作閾值（Resting Motor Threshold, RMT），以80%、100%及120%三種不同強度隨機施予單脈衝TMS刺激，並分別於睜眼與閉眼兩種狀態下進行測試。皮質興奮性評估指標包括運動誘發電位（Motor-Evoked Potentials, MEPs）與TMS誘發電位（TMS-Evoked Potentials, TEPs）；而測量動態的神經振盪則採用試次間相位相干性（Inter-Trial Phase Coherence, ITPC）及腦區間相位叢集性（Inter-Site Phase Clustering, ISPC）進行分析。同時，本研究運用以經驗模態分解（Empirical Mode Decomposition, EMD）為基礎之希爾伯特-黃轉換（Hilbert-Huang Transform）分析及全息希爾伯特跨頻跨腦區相位耦合（Holo-Hilbert Cross-Frequency Phase Clustering, HHCFPC）等進階訊號處理技術，以期提高數據解析精度。本研究結果指出，提升TMS刺激強度可使運動誘發電位（MEP）振幅一致性地增加，顯示皮質脊髓興奮性隨刺激強度之提升而同步增強，且此效應不受眼睛狀態（睜眼或閉眼）的影響。針對TMS誘發電位（TEP）成分（P30、N45、N100）之分析進一步揭示出顯著的刺激強度依賴性調控效應：於睜眼狀態下，高強度（120% RMT）刺激能促使早期皮質興奮成分（P30）與MEP振幅之間呈現更為顯著的正相關；相對地，於閉眼狀態下則較易誘發皮質抑制機制，表現為在高強度刺激條件下，alpha波段試次間相位同步性（ITPC）與N100振幅間呈現負相關性。從網路層面的腦區間相位叢集性（ISPC）分析結果顯示，在閉眼狀態下，以120% RMT強度刺激時，運動皮質區與額葉及中央-頂葉區域間呈現顯著的狀態與刺激強度依賴性theta-gamma相位耦合現象，進一步突顯內在振盪溝通與功能整合之機制。相對地，於睜眼狀態下並未觀察到相同現象，暗示感官驅動的皮質處理可能會干擾內在網絡的同步性。。本研究結果顯示，TMS 調控大腦皮質興奮性與神經網絡動態呈現明顯的層次性及狀態依賴性。具體而言，較高刺激強度主要能增強局部皮質的興奮性與相位同步性；而在不同皮質狀態下，興奮與抑制機制以及局部與全局網絡運作均呈現顯著且差異性的調控效應。此一發現不僅豐富了我們對大腦基礎狀態與神經調控技術交互作用的瞭解，更為臨床應用及實驗性 TMS 方案之優化提供了關鍵參考依據。 ;Transcranial Magnetic Stimulation (TMS) has been extensively utilized in neuroscience to investigate cortical excitability and neural network dynamics non-invasively. This study systematically explores how TMS intensity and brain state (eyes open, EO, and eyes closed, EC) conditions influence cortical excitability and functional connectivity using concurrent TMS and electroencephalography (EEG) recordings. Single-pulse TMS was administered over the left primary motor cortex (M1) at varying intensities (80%, 100%, and 120% of the resting motor threshold, RMT) in randomized order under both EO and EC conditions. Cortical excitability was measured via motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs), while neural oscillatory dynamics were assessed through inter-trial phase coherence (ITPC) and inter-site phase clustering (ISPC), employing advanced signal processing techniques including Empirical Mode Decomposition (EMD)-based Hilbert-Huang Transform, Event-Related Mode (ERM) analysis, and Holo-Hilbert Cross-Frequency Phase Clustering (HHCFPC). Results show that increasing TMS intensity consistently augmented MEP amplitudes, reflecting heightened corticospinal excitability independent of brain state. Analysis of TEP components (P30, N45, N100) revealed significant intensity-dependent modulation, with the EO condition at high stimulation intensity (120% RMT) facilitating stronger correlations between early cortical excitation (P30) and MEP amplitude. Conversely, the EC state preferentially promoted inhibitory cortical mechanisms, as evidenced by a negative correlation between alpha-band ITPC and N100 amplitude at higher stimulation intensities. Network-level analyses via ISPC indicated robust state- and intensity-dependent theta-gamma phase coupling between M1 and frontal/centro-parietal regions exclusively under EC conditions at 120% RMT, emphasizing intrinsic oscillatory communication and functional integration. Such coupling was absent in EO conditions, suggesting sensory-driven cortical processing disrupts intrinsic network synchronization. These findings underscore a hierarchical, state-dependent modulation of cortical excitability and network dynamics by TMS. Higher stimulation intensities primarily enhance local excitability and phase coherence, with distinct cortical states differentially influencing excitatory versus inhibitory and local versus global network processes. This study may advance our understanding of how brain states and TMS intensity influence motor cortex excitability and global functional connectivity, thereby providing critical insights for optimizing both clinical and experimental TMS protocols.
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