用動態因果模型分析間斷性Theta爆發刺激對上肢運動神經網路的調變

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邱昱豪(Yu-Hao Ciou) 查詢紙本館藏

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生醫科學與工程學系

論文名稱

用動態因果模型分析間斷性Theta爆發刺激對上肢運動神經網路的調變
(Using dynamic casual model to analysis the modulation of upper motor neural network by iTBS)

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摘要(中)

磁爆發刺激(TBS)透過電磁刺激器線圈對大腦皮質進行刺激，利用不同的刺激程序，對皮質產生興奮性或抑制性的調節。先前研究指出，間斷性iTBS會產生興奮性調節，但因為受測者間的個體差異，導致iTBS影響皮質的效果沒有一致性。因此，本研究預計以大腦運動神經網路功能性連結的變化，探討經過興奮性脈衝程序刺激之神經網路被調變的機轉，以找出影響個體差異的關鍵因子。
本研究招募16名健康受測者，每次實驗會以視覺誘發來進行肩關節伸展的上肢運動，作為神經網路變化的基礎。並且在施打iTBS前後分別量測受測者的腦電波(EEG)。在磁刺激的實驗會以600脈衝量(pulse)的iTBS為一次程序，每次間隔3分鐘，給予受測者3次的刺激程序，共1800脈衝量的iTBS施打於運動手對側的初級運動皮質(M1)腦區。分析上，使用腦電波得到的前後測資料，進行動態因果模型分析，並根據iTBS可能的影響效果，將運動網路模型以LM1為影響起點，分成調變方向為buttom-up 或botton-up+top-down 調變與是否僅限同側 (LPM和SMA )、擴及對側(RM1, LPM和SMA)或整個網路都被調變，建構了8種可能的影響模型(調變方向分單向及雙向連結方式)，以分析iTBS對於上肢運動的神經網路變化。
結果顯示受到iTBS1800影響後的模型，LM1與RM1腦區的雙向調變模型為優勢。其中，LM1會促進非刺激腦區RM1的興奮，造成RM1在動作誘發後60~180毫秒間β波段的增強，至關重要的是，這種興奮性β波power調節增強的效果與受試者前測時神經網路狀態的強度呈現負相關。除此之外，在LM1的事件相關非同步的β波強度下降，是大腦皮質興奮性增強表現。先前研究顯示，LM1對RM1在β波的增強有助於中風後的功能回復，因此，我們認為iTBS1800確實能用於改善中風後的功能。另外，在RM1對LM1的腦區連結，以γ、α的連結為主，而γ→α與前測的神經網路強度呈現正相關性，推測此連結受到iTBS調節後，可能對運動時的精準控制和專注力有正向變化。但是在γ對γ波的顯著連結則沒有任何相關性，且在LM1的power spectrum中同樣沒有任何顯著的變化，顯示此連結被iTBS的調變與前測時的狀態無關，說明該連結存在運動控制不受個體差異的影響。
總結以上結果，iTBS1800對於LM1的事件相關非同步β波減少，可能是反映LM1興奮性增加，及iTBS1800透過LM1對促進RM1的β波增加，顯示了iTBS1800對非刺激區亦有興奮性調節的效果，並且，這種興奮性β波power調節增強的效果，與受試者前測時神經網路狀態的強度呈現負相關。此外iTBS1800對於γ也有興奮的效果，而且，其效果不受個體差異影響。預計未來方向可往(1)不同實驗控制的效果; (2)促進中風復原的研究，對於患側興奮性不好的病人，我們推測施打患側，以增強患側興奮性效果，改善對於運動障礙的併發症。而在α、γ波的研究結果，iTBS1800對於病人運動行為的專注力與精準度治療，可以作為運動動力學指標的參考結果。

摘要(英)

Noninvasive brain stimulation technique like theta bursts stimulation (TBS) can alter the states of brain activity. The applications of intermittent TBS (iTBS) over the motor-associated cortex have been shown to increase the excitatability as measured with MEPs. However, the high inter-indivisual variability in terms of the induced cerebral plasticity both in healthy controls and stroke patients limits its clinical applications. Therefore, this study aims to investigate the frequency-specific alternations of the motor network after iTBS and identify the factors that are responsible for the individual differences in iTBS after-effects.
The study recruited 16 healthy subjects. EEG experiments were conducted twice - before and after iTBS which was seven days apart. The subjects were instructed to perform visualy cued shoulder flextion and extension for 90 times. The inter-trial interval is 8±1 seconds. 32 channel EEG were acquired with 1000 Hz sampling rate during the movement task. In the iTBS, a 2 s train of TBS is repeated every 10 s for a total of 190 s (600 pulses) over primary motor cortex (M1) and this pecedure is repeated for 3 tims (1800 pulse). We use dynamic causal modeling (DCM) of induced response to model the iTBS elicted moudulatory effect on the motor network.
The analytical results show that the reciprocal modulations between the left and the right M1 can best explan the iTBS effects. Specifically, iTBS over LM1 exerts excitatory effects on RM1, resulting in β-band enhancement after movement onset between 60 ~ 180 milliseconds in RM1. Importantly, this moudulation effect is negatively correlated with the intrinsic coupling strength between LM1 beta activity and RM1 beta activity at baseline (i.e. before iTBS). In addition, RM1 γ activity promotes LM1 α activity and this coupling is positively correlated with the intrinsic coupling strength between them. Finally, there is a significant effect on the increase of LM1 γ activity enhanced by the RM1 γ activity, which is irrelevant to the baseline condition. Furthermore, we observed that LM1 beta event-related desynchronzations (ERD) decreases after iTBS, indicating the increased excitability of the LM1.
In conclusion, iTBS1800 can induce the enhancement of β oscillation at RM1, and γ oscillation at LM1 and RM1. Moreover, the effect of iTBS shows individual differences. The future direction can be (1) the intensity effect of iTBS and (2) the design of customed iTBS protocol to promote the recovery after stroke.

關鍵字(中)

★ Theta 磁爆發
★ 動態因果模型
★ 初級運動皮質區
★ 上肢運動網路調變
★ 個體差異性

關鍵字(英)

★ Theta magnetic burst
★ dynamic causal model
★ primary motor cortex
★ upper limb motor network modulation
★ individual difference

論文目次

致謝 I
摘要 II
Abstract IV
目錄 VI
表目錄 IX
圖目錄 X
第一章緒論 1
1.1 研究背景與動機 1
1.2 研究目的 1
1.3 論文架構 2
第二章文獻回顧 3
2.1 腦電波與臨床研究 3
2.1.1 神經電生理與腦電波 3
2.1.2 國際10-20系統 4
2.1.3 腦電波圖與頻帶 5
2.2 經顱磁刺激與大腦皮質研究 7
2.2.1 經顱磁刺激介紹 7
2.2.2 動作誘發電位 8
2.2.3 運動皮質與經顱磁刺激研究 9
2.3 間斷式Theta爆發刺激 11
2.3.1. 間斷式Theta爆發介紹 11
2.3.2. 間斷性Theta經顱磁刺激(iTBS)對運動皮質研究 12
2.3.3. 間斷性Theta經顱磁刺激(iTBS)對神經網路研究 15
2.4 動態因果模型 17
2.4.1. 動態因果模型介紹 17
2.4.2. 功能性連結與有效性連結 17
2.4.3. 誘發響應的動態因果模型 18
2.4.4. 線性/非線性效應 20
第三章實驗設計與研究方法 22
3.1 受測者條件 22
3.2 實驗設備 23
3.2.1. 硬體設備 23
3.2.2. 軟體設備 24
3.3 實驗流程 25
3.4 腦波實驗 27
3.5 研究資料 28
3.6 資料分析方式 29
3.7 動態因果模型建構 30
3.7.1. 動態因果模型設計 30
3.7.2. 動態因果模型建立 31
3.7.3. 動態因果模型選擇 32
3.8 DCM特徵分析 33
第四章研究結果 37
4.1 原始資料處理 37
4.2 腦電波調整及統計結果 38
4.3 初級運動皮質(M1)動態因果模型分析結果 43
4.3.1. 動態因果模型選擇結果 43
4.3.2. 調整後對模型選擇 47
4.3.3. iTBS對神經網路的影響 49
4.3.4. 大腦神經網路連結調節結果 52
4.3.5. 大腦神神經網路對大腦腦波變異值影響結果 55
4.3.6. 頻率連結的強度相關性 58
4.4 M1腦區的頻率強度變化 62
4.5 M1神經網路連結選擇與模型建構 64
第五章結果討論與結論 66
5.1 動態因果模型分析iTBS對神經網路調變 66
5.2 iTBS對神經網路的個體變異性 68
5.3 iTBS1800對病患的效果 69
5.4 結論 70
第六章未來展望 71
第七章參考文獻 73
附件 79

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指導教授

陳純娟(Chun-Chuan Chen)

審核日期

2017-10-16

推文