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研究生: 謝汶宏
Siah, Boon Hong
論文名稱: θ波段間歇性電刺激於腹側海馬連合以抑制癲癇
Acute suppression of Seizure by Theta-Burst Stimulation at Ventral Hippocampal Commissure
指導教授: 朱銘祥
Ju, Ming-Shaung
學位類別: 碩士
Master
系所名稱: 工學院 - 機械工程學系
Department of Mechanical Engineering
論文出版年: 2013
畢業學年度: 101
語文別: 英文
論文頁數: 80
中文關鍵詞: 急性癲癇θ波間歇性電刺激4-氨基吡啶海馬回
外文關鍵詞: acute seizure, theta-burst stimulation, 4-AP, hippocampus
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  • 腦深層電刺激術為一個有發展潛能的急性癲癇抑制方法。過去在很多研究當中,尤其是動物實驗,高頻連續電刺激為主要被應用於急性癲癇抑制的電刺激方式。然而,電刺激的真正機制尚未完全了解,短時間內給予大腦過量的電刺激可能會造成不可復原的傷害。因此,更有效率的電刺激方式,既使用相對少的電量但卻可以達到同樣的效果,是有需要的。θ波間歇性電刺激把傳統的高頻連續電刺激分割於每0.2秒給予一定量的電刺激,已於其他腦神經疾病被證實為相當有效率的電刺激方式,但此電刺激方式仍未被應用於癲癇急性抑制。因此,我們首先進行一系列的開迴路電刺激實驗以印證其抑制癲癇之效果並且找出θ波間歇性電刺激的最佳參數。在進行實驗的時候,我們使用4-氨基吡啶(4-aminopyridine)直接注射於大鼠右側海馬回以誘發急性癲癇。而電刺激位置則選擇在與海馬回有著大量連結的腹側海馬連合。之後,我們將最佳化參數的θ波間歇性電刺激和傳統連續高頻電刺激應用於閉迴路癲癇抑制電刺激系統,然後比較兩者結果。我們發現θ波間歇性電刺激相較於傳統高頻電刺激,可使用更少的電量去控制同樣的急性癲癇。因此,我們總結θ波間歇性電刺激為比較可行的急性癲癇抑制的電刺激方式。

    Deep brain stimulation (DBS) is a potential therapy for acute seizure control. In animal studies, DBS is generally performed using a continuous high frequency stimulation (cHFS) protocol, however, the enormous current charge delivered to the brain in cHFS may result in irreversible physical damage. While theta-burst stimulation (TBS), which separates continuous electrical stimulation into burst stimulation that repeated in every 0.2s, has been proven to be more effective than cHFS in treating neurological disorders such as Parkinson’s disease, strokes, and multiple sclerosis, its effectiveness in treating epilepsy is unclear. Accordingly, in this thesis, a series of open-loop experiments are first performed to determine the optimal TBS protocol for the treatment of epilepsy. In the animal experiments, 4-aminopyridine (4-AP) is injected into the right hippocampus of Sprague-Dawley rats in order to induce an acute seizure condition and the effectiveness of various TBS protocols in terminating the seizures is then analyzed in terms of the current delivered to the ventral hippocampal commissure. A closed-loop seizure control system based on the optimal TBS protocol is then implemented. The results show that TBS provides an effective means of suppressing seizure and requires a lower current charge than cHFS. As a result, it is concluded that TBS provides a more practical therapy than cHFS for suppression of epilepsy.

    Table of Contents 摘要 I Abstract II 致謝 III Table of Contents IV List of Figures VII List of Tables X Chapter 1 Introduction 1 1.1 Background 1 1.1.1 Status Epilepticus 2 1.1.2 Deep Brain Stimulation 3 1.1.3 Theta-Burst Stimulation 5 1.2 Literatures Review 7 1.3 Motivation and Objectives 10 1.4 Thesis Organization 12 Chapter 2 Open-loop stimulation for optimizing parameters 13 2.1 Experiment Design 13 2.2 Experiment Implementation 16 2.2.1 Animal Model 16 2.2.2 Electrodes Implantation Sites 17 2.2.3 Experiment Apparatus 20 2.2.4 Software & User Interface 22 2.2.5 Experiment Procedures 24 2.3 Artifacts Removal Algorithm 26 2.4 Performance Indices 31 2.5 Results 34 2.5.1 4-AP induced epileptic model 34 2.5.2 Seizures suppression by TBS 36 2.5.3 Suppression rates 37 2.5.4 Post-Stimulation Effective Time 41 2.5.5 Regional Suppression Rates 43 Chapter 3 Closed-loop Implementation based on TBS protocol 44 3.1 Experiment Design 44 3.2 Spikes detection algorithm 48 3.3 Closed-loop Experiment Implementation 50 3.4 Performance Indices 52 3.5 Results 54 3.5.1 Cumulative charge 56 3.5.2 Post-Stimulation Effective Time 57 Chapter 4 Discussions 58 4.1 Effects of 4-AP on the rat’s brain 58 4.2 Conversion of seizure pattern 59 4.3 Optimal parameters of TBS 62 4.4 Regional Suppression Rate 65 4.5 Spike detection algorithm 67 4.6 Comparison of TBS and cHFS 69 4.7 Normality of Distribution of Data 71 Chapter 5 Conclusion and future works 74 5.1 Conclusion 74 5.2 Future works 74 References 76 Appendix 80

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