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作者:黃冠樺
作者(外文):Guan-Hua Huang
論文名稱:重複性穿顱磁刺激對於憂鬱症患者的腦區結構改變
論文名稱(外文):Structural brain changes with repetitive transcranial magnetic stimulation in major depressive disorder
指導教授:陳麗芬
指導教授(外文):Li-Fen Chen
學位類別:碩士
系所名稱:腦科學研究所
學號:39830015
出版年:102
畢業學年度:101
語文別:英文
論文頁數:37
中文關鍵詞:背外側前額葉憂鬱症眼框額葉皮質重複性穿顱磁刺激基於體素型態分析方法
外文關鍵詞:DLPFCMDDOFCrTMSVBM
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背景:重度憂鬱症(MDD)治療主要是以藥物為主,但是對於某些患者是無效的。重複透顱磁刺激(rTMS)療法提供給藥物難治型病人,另一個治療方法。基於rTMS影響MDD患者的大腦結構改變的研究較少,本研究將針對rTMS治療在MDD患者的臨床憂鬱資料與大腦結構之間的關係做一探討。我們假設rTMS對患者的病況改善,與其大腦結構改變有一相關性。
資料與方法:30位患者在進行高頻(10Hz)施打於左背側前額葉皮質的rTMS療程前、兩周療程後,利用憂鬱分數(HDRS)下降達50%來區辨治療效果。 病患的施打rTMS前後的T1加權影像,利用基於體素的形態學分析(VBM)比對rTMS施打前後腦結構上灰質體積的差異,另外也與40位正常人的腦結構影像進行比較。接著計算患者在rTMS療程前後,腦區灰質改變量與患者臨床資料兩者間的相關性。最後針對rTMS治療前後病患,在統計結果上腦區結構有差異的區域,取出病患治療前的體積,作為建構預測療效的模型-羅吉斯回歸分析上的參數。
結果:經由兩週的rTMS治療後,十七位患者為治療有效者,十三位患者為治療無效者。在治療有效者的腦區改變結果上,腦區體積增加的區域有兩側的眼眶皮質,右側中額葉,右側下聶葉,及右側楔前葉。其中兩側的眼眶皮質的體積增加量,與患者的憂鬱分數下降量呈現證相關。腦區減少的區域有右側小腦,右側上聶葉,左側下額葉,及兩側的腦島。而在這些區域治療後的體積,與正常人同區域的體積沒有顯著差異。另外在rTMS療效的預測模型上,最後預測療效的正確率達到百分之九十三點三。
結論:兩週的rTMS治療對於治療有效者,其兩側的眼眶皮質增加量與療效有關。在治療前的病患部份大腦灰質體積,可作為rTMS療效的預測參數。
Background: For major depressive disorder (MDD), drugs are the major treatment approach, but there are ineffective for drug-resistant patients. Repetitive transcranial magnetic stimulation (rTMS) provides another alternative therapy to these drug-resistant patients.
Materials and Methods: Thirty MDD patients were accepted high frequency (10Hz) rTMS over the left dorsolateral prefrontal cortex during two weeks, and to determined as responder by 50% decreased Hamilton Depression Rating Scale (HDRS). T1-weighted magnetic resonance images (two time points per patient, pre-treatment,week-0, and after treatment, week-2) will be compared to detect brain grey matter differences by voxel-based morphometric analysis. And there are forty subjects for normal control. Secondly, to calculate the correlation between that the grey matter difference between week-0, and week-2 and patients’clinical data before and after rTMS treatment difference. Finally, to find the significant different regions between week-0 and week-2 as cluster of interest (COI), the predicted model would be constructed by Binary Logistic Regression whose variables were computed from patient's week-0 COI volumes.
Results: During two weeks rTMS therapy, seventeen patients were as responder, thirteen patients were as non-responder. In responder, the significant volume increased regions were bilateral orbitofrontal cortex, right middle frontal gyrus, right inferior temporal gyrus, and right precuneus. The positive correlation was observed between increased bilateral orbitofrontal cortex volumes and decreased HDRS.  The significant volume decreased regions were right cerebelum, right superior temporal pole, left inferior frontal gyrus, and bilateral insula. Finally, in predicted model of rTMS therapy, the percentage of correction was 93.3%.
Conclusions: Two weeks rTMS therapy for responder, the increased bilateral orbitofrontal cortex volumes are high relationship with rTMS treatment effect. The parts of gray matter volume could be variables in predicted model.
論文電子檔著作權授權書...i
論文審定同意書...ii
致謝...iii
中文摘要...iv
英文摘要...v
目錄...vi
圖目錄...x
表目錄...xi
第一章 背景...1
1.1 Major Depressive Disorder...2
1.1.1 A Clinical Introduction to Major Depressive Disorder...2
1.1.2 Deficits of Brain Structure of Major Depressive Disorder...3
1.2 Repetitive Transcranial Magnetic Stimulation (rTMS)...3
1.2.1 A Introduction of Repetitive Transcranial Magnetic Stimulation...3
1.2.2 Comparison of Active rTMS versus Sham rTMS...5
1.3 Voxel-based morphometry(VBM)...5
1.4 Thesis Scope...6
第二章 資料與方法...7
2.1 Participants...8
2.2 Repetitive Transcranial Magnetic Stimulation rTMS protocol...9
2.3 Magnetic resonance image acquisition...11
2.4 VBM processing...12
2.5 Statistical analysis...14

第三章 結果...16
3.1 Participants data...17
3.2 VBM results...17
3.3 Prediction and Correlation results...21

第四章 討論...27
第五章 結論...32
參考文獻.......34


List of Figures

Figure 1 rTMS device and MDD patient receiving rTMS treatment............................................9
Figure 2 Two time points of MRI scan and rTMS treatment in MDD patients..........................10
Figure 3 rTMS stimulation site..................................10
Figure 4 VBM procedure in SPM8........................13
Figure 5 VBM result in all patient..................22
Figure 6 VBM result in responder...................22
Figure 7 VBM result in non-responder...................23
Figure 8 All subjects gray matter volume in responders' increased regions........24
Figure 9 All subjects gray matter volume in responders' decreased regions........24
Figure 10 All subjects gray matter volume in non-responders' increased regions.........25
Figure 11 All subjects gray matter volume in non-responders' decreased regions................25
Figure 12 Correlation between significant increased GM difference and HDRS difference......26


List of Tables

Table 1 Demographic data in patients with responders, non-responders and normal control......18
Table 2 Regions of GM volume comparison before and after rTMS therapy in all patients.......19
Table 3 Regions of GM volume comparison before and after rTMS therapy in reponders.........20
Table 4 Regions of GM volume comparison before and after rTMS therapy in non-reponders..21
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