瞭解大腦功能性的連接以及在不同狀態下的皮質活動，在設計針對神經疾病的治療方法時扮演著關鍵的角色。而在無數的神經疾病中，中風在全球是一個導致死亡以及失能的主要原因。高精度經顱直流電刺激術已被證實為進行神經調控的潛在治療方法。因此我們將陣發脈衝刺激框架導入高精度經顱電刺激系統，並且研究其對人類大腦的神經活動影響。在無數的神經影像技術中，功能性近紅外光譜是一種非侵入式的血氧動力反應量測方法。在此研究中最主要的目的是利用功能性近紅外光譜來評估以下兩個事件的大腦半球間的同步狀態以及皮質活動在不同嚴重性以及期程的急性缺血性中風患者及高精度經顱電刺激於健康受試者。
研究一：招募23名缺血性腦中風患者參與研究。根據入院時的NIHSS中風量表將參與者分為三組，包括重度中風（7 名患者）、中度中風（9 名患者）和輕度中風（7 名患者）。所有受試者在中風後第一周和第三周參加了快速手指敲擊任務的實驗，並且使用 20 通道的fNIRS系統測量雙側前額葉皮層、輔助運動區和感覺運動皮層的血流動力學變化。測量時間同步活動的半球間相關係數(Interhemispheric Correlation Coefficient, IHCC)以及測量時頻相位活動的小波相位相干性(Wavelet Phase Coherence, WPCO)被用來反映一個區域內兩個半球之間的對稱性。而藉由運動任務下，量測血氧濃度的平均值用於反映不同皮質區域的活動狀態。在中風後第三週，嚴重中風患者的第三以及第四頻帶的大腦半球間對稱性低於輕度中風患者。此外，在第1週的中重度中風患者中，患側皮質活動顯著低於健側。然而，在第三週的中重度中風，患側半球的感覺動作皮質區反應有顯著增強。
研究二：招募15名右側慣用手的健康成人參加三個HD-tES的實驗（2 毫安培，刺激時間10分鐘），受試者分別接受單側、雙側以及安慰劑腦陣發經顱刺激。並且在刺激前、中、後分別利用手指敲擊運動以量測動作事件誘發皮質活動。在實驗的每個階段，並且利用fNIRS系統記錄雙側前額葉、感覺動作皮質以及頂葉的血流動力學響應。雙腦電刺激的方法下，感覺動作皮質區的IHCC和WPCO在第三與第四頻帶的反應顯著低於刺激前後以及其他種刺激方法。此外，在促進性刺激以及雙腦刺激的方法中，由快速手指敲擊任務誘發的感覺動作皮質活動顯著大於準備階段與安慰劑刺激組別。然而，此促進現象僅於雙腦刺激中發現。
我們的研究結果表明，fNIRS可用作早期中風評估和評估中風後恢復效果以及非侵入式皮質刺激效果的工具。我們進一步證明了雙腦經顱刺激方法在調節靜態大腦半球同步和促進運動任務誘發的皮層活動方面的有效性。研究結果表明，雙側經顱電刺激方案可能是一種新的治療方法，用於誘導神經調節對缺血性中風或創傷性腦損傷引起的各種神經系統疾病的影響。

Understanding brain functional connectivity and cortical activation in various conditions is a crucial factor for designing therapeutic treatments for neurological disorders. Among various neurological disorders, stroke is a major cause of death and impairments worldwide. High-definition transcranial direct current stimulation (HD-tDC) has been proposed to be a potential therapeutic for modulating brain function in humans. Herein, we extended the theta-burst stimulation (TBS) schemes to high-definition electrical stimulation (HD-TBS) and investigated its neural effects on the human brain. Among a number of neuroimaging techniques, near-infrared spectroscopy (NIRS) appears as a non-invasive technique for recording hemodynamic responses in humans. The main purposes of the current study were to use NIRS for evaluating resting-state interhemispheric synchronization and cortical activity induced by motor tasks in acute ischemic stroke patients with different degrees of severity and post-stroke stages. Also, the same measurement methods were applied to investigate effects of HD-TBS on healthy subjects.
For interhemispheric symmetry in stroke, twenty-three ischemic stroke patients were recruited to participate in the study. Participants were divided into three groups including severe-stroke (7 patients), moderate-stroke (9 patients) and minor-stroke (7 patients) based on their National Institutes of Health Stroke Scale (NIHSS) at admission. All patients participated in the experiments with 5-min resting-state and 5-min speed finger-tapping tasks in a sitting position at week-1 and week-3 after stroke onset. A 20-channel NIRS system was used to record cortical hemodynamic changes in the bilateral prefrontal cortex (PFC), the supplementary motor area (SMA), and the sensorimotor cortex (SMC). The cortical symmetry between the two hemispheres within a region in the resting-state was evaluated by both time-domain interhemispheric correlation coefficient (IHCC) and time-frequency domain wavelet phase coherence (WPCO). Averaged of oxyhemoglobin concentration in motor task condition was used to reflect activity in different cortical regions. Both IHCC and WPCO indicated a lower interhemispheric symmetry in activities of bands III and IV in the severe-stroke group than those in minor-stroke group in week-3 measurement. In addition, cortical activity in all measurement regions in the affected hemisphere was significantly lower than that in the unaffected hemisphere in the moderate-severe group in week-1 post-stroke. However, patients in the moderate-severe group showed significant improvement in the affected SMC activation in week-3 measurement.
For HD-TBS on the brain, fifteen right-handed healthy adults were recruited to participate in three HD-TBS protocols (2 mA, 10-min): Unilateral (Uni)-iTBS, Bilateral (Bi)-cTBS/iTBS, and sham. Experimental tasks including 5-min resting-state and 5-min speed finger-tapping tasks were performed in three phases: before HD-TBS (pre), during HD-TBS (during), and after HD-TBS (post). A 20-channel NIRS system was used to recorded hemodynamic response in the bilateral PFC, SMC, and parietal lobe (PL) at each phase of the experiment. The IHCC and WPCO in the SMC region under Bi-cTBS/iTBS protocol showed significantly lower in bands III and IV than those in the pre and post- stimulation as well as other HD-TBS protocols. In addition, the SMC activation induced by speed finger-tapping tasks at during HD-iTBS and HD-cTBS/iTBS protocols were significantly greater than those in the pre-phases and sham protocol. However, the long-lasting effects was only found in the HD-cTBS/iTBS approach.
In summary, our findings suggest that NIRS could be used as a rapid tool for early stroke assessment and evaluation of the efficacy of post-stroke rehabilitation as well as the effectiveness of non-invasive cortical stimulation. We further demonstrated the effectiveness of the bilateral HD-TBS approach in modulating resting-state interhemispheric synchronization and facilitating cortical activation induced by motor tasks. These findings suggest that the bilateral HD-TBS protocol could be a novel therapeutic for inducing the effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

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