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研究生:段旭玶
研究生(外文):Hsu-Ping Tuan
論文名稱:以重複性穿顱磁刺激治療憂鬱症病患之3個月腦磁波追蹤研究
論文名稱(外文):A 3-Month Follow-Up Magnetoencephalographic Study of Repetitive Transcranial Magnetic Stimulation in Major Depression
指導教授:蘇東平蘇東平引用關係陳麗芬陳麗芬引用關係
指導教授(外文):Tung-Ping SuLi-Fen Chen
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:腦科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:99
語文別:英文
論文頁數:84
中文關鍵詞:重度憂鬱症重複性穿顱磁刺激腦磁波
外文關鍵詞:major depressive disorderrepetitive transcranial magnetic stimulationmagnetoencephalography
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背景:重複性穿顱磁刺激(rTMS)為非侵入式醫療儀器,具有短期抗憂鬱效果,可用於治療藥物難治型憂鬱症病患。然而只有少數研究探討rTMS對腦波的長期影響。本研究欲檢驗rTMS對重度憂鬱症病患憂鬱症狀與休息狀態腦波的長期影響,我們假設rTMS具有長期抗憂鬱效果和使腦波持續改變。
資料與方法:三十位藥物難治型重度憂鬱症病患在兩週內接受10次施打於左背側前額葉皮質的高頻(10Hz)rTMS療程。三十位中有二十三位病患在治療前後和三個月後成功收錄三分鐘眼睛睜開時休息狀態腦磁波,另外亦收錄五十位年齡相符的健康受試者腦磁波為對照組。我們將去雜訊的腦磁波進行頻譜分析,區分成五個頻帶:delta (2-4Hz), theta (4-8Hz), alpha (8-13Hz), beta (13-30Hz) , 與gamma (30-50Hz)。利用組內無母數統計分析法Friedman analysis of variance檢測病患治療前後頻帶振幅變化,無母數分析檢測法Mann-Whitney U tests用以比較組間腦波振幅差異,二元邏輯迴歸分析以頻帶振幅預測治療反應。
結果:在兩週rTMS療程結束後,三十位中有十七位病患為治療有效者,其中十四位在三個月後依然為治療有效者。在治療前憂鬱量表分數與低頻腦波振幅大小呈現負相關。根據組內分析結果,只有治療有效者在三個月後其delta腦波振幅顯著上升。同時,治療有效者在治療前的delta腦波振幅顯著低於對照組,然而rTMS治療消除了該組間在全腦的delta腦波振幅差異。在施打rTMS前後與正常對照組相較底下delta腦波振幅差異皆為顯著較小。另外,位於中腦與枕葉的theta腦波振幅具有預測治療效果最高的指標。
結論:施打左背側前額葉rTMS,對憂鬱症病患的腦波有持續性變化的影響。

Background: Repetitive transcranial magnetic stimulation (rTMS) has been suggested as a potential non-invasive tool for exerting short-term antidepressant effects in medication-resistant depressed patients. However, few studies investigate long-term effects of rTMS on oscillatory neuromagnetic activity. The present study aims at examining the lasting influence of rTMS on spontaneous brain rhythms in patients with major depressive disorder (MDD). We hypothesize that rTMS treatment could exert not only long-term clinical improvement but also lasting oscillatory changes in depressed patients.
Materials and Methods: Thirty medication-resistant MDD patients were applied 10-session high-frequency rTMS (10Hz) over the left dorsolateral prefrontal cortex within two weeks. Twenty-three of 30 patients underwent three-minute resting magnetoencephalography (MEG) recordings with eyes open at pretreatment, the end each rTMS therapy week and after 3 months. Resting MEG data of 50 age-matched healthy controls were also recorded. The noise-free MEG signals were processed by amplitude spectrum density analysis and decomposed into five different frequencies: delta (2-4Hz), theta (4-8Hz), alpha (8-13Hz), beta (13-30Hz) and gamma (30-50Hz). Friedman analysis of variance was used for within-group analysis to examine relative band amplitude changes between each data point. Mann-Whitney U tests were conducted to investigate oscillatory amplitude differences between groups. A logistic regression was employed to evaluate the prognostic value of amplitude of each band for the treatment response.
Results: Among the 30 patients, 17 were treatment responders after 2-week rTMS therapy, and 14 patients remained responders after 3 months. There were negative correlations between depression ratings and slow-wave oscillations as well as neuropsychological outcomes and slow-wave oscillations. As for within-group analysis, increased relative delta amplitude was found only in the responders at 3 months. Before treatment, delta amplitude in the responder was significantly lower than that in controls. rTMS altered the abnormalities in delta oscillations, and thus the group differences of delta amplitude between controls and the responders were diminished in all the brain regions. Relative theta amplitude in the central and occipital regions had greatest prognostic value for treatment response.
Conclusions: Our findings indicated that high-frequency rTMS over the left dorsolateral prefrontal cortex had lasting influence on MDD patients in terms of changes of neural synchronization especially delta oscillations.


Signature Page...i
Thesis Approval Form....ii
Acknowledgments...iii
Chinese Abstract...iv
English Abstract...v
Table of Contents...x
List of Figures...xiii
List of Tables...xiv
Chapter 1 Introduction...1
1.1 Major Depressive Disorder...2
1.1.1 A Clinical Introduction to Major Depressive Disorder...2
1.1.2 Deficits of Cognitive Function and Neural Substrates in MDD...3
1.2 Repetitive Transcranial Magnetic Stimulation...4
1.2.1 An Introduction to TMS and rTMS...4
1.2.2 Comparison of rTMS and ECT Therapy...5
1.2.3 rTMS in the Treatment of Depression ...6
1.2.4 Comparison of Active rTMS versus Sham rTMS...7
1.2.5 Therapeutic Efficacy of rTMS at Different Frequencies...7
1.2.6 Therapeutic Efficacy of rTMS at Different Intensities...9
1.2.7 Follow-up rTMS Studies...10
1.3 An Introduction to Magnetoencephalography...11
1.4 Brain rhythms...14
1.4.1 Slow-wave Oscillations...15
1.4.2 Fast-wave Oscillations...16
1.5 Thesis Scope and Organization...16
Chapter 2 Methods and Materials...18
2.1 Subjects...19
2.2 Study Design...20
2.3 rTMS Treatment...21
2.4 Clinical Assessment...22
2.5 Neuropsychological Tests...23
2.6 MEG Data Acquisition....23
2.7 MEG Data Analysis...24
2.8 Statistics...26
Chapter 3 Results...29
3.1 Clinical Outcomes...30
3.1.1 Primary Outcomes...30
3.1.2 Secondary Outcomes...30
3.2 Neuropsychological Outcomes...34
3.3 Neuroimaging Results...36
3.3.1 Correlation between Oscillation and Depression Rating ...36
3.3.2 Correlation between Frequency Bands...39
3.3.3 Correlation between Oscillation and Neuropsychological Outcomes...41
3.3.4 Short-term rTMS Effects on Brain Oscillations...43
3.3.5 Long-term rTMS (3-month) Effects on Brain Oscillations...46
3.3.6 Comparison of MDD Patients and Healthy Controls...47
3.3.7 Short-term rTMS Effects on Functional Connectivity...59
3.3.8 Dynamical Prognostic Model for Treatment Outcome...60
3.3.9 Relative versus Absolute Amplitude Spectrum Density...65
3.3.10 Converted Cases...68
Chapter 4 Discussion ...70
Chapter 5 Conclusions...76
References...79


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