陣發式穿顱磁刺激於重度憂鬱症之治療：功能性磁振造影研究

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题名:	陣發式穿顱磁刺激於重度憂鬱症之治療：功能性磁振造影研究 Theta Burst Stimulation Treatment for Major Depressive Disorder: An fMRI Study.
作者:	謝宛庭;Wan-Ting Hsieh
贡献者:	神經科學與認知科學研究所碩士班
关键词:	重度憂鬱症;穿顱磁刺激;磁振造影;治療;MDD;TBS;fMRI;treatment
日期:	2015-07-01
上传时间:	2016-01-08 15:23:23 (UTC+8)
出版者:	中國醫藥大學
摘要:	重度憂鬱症（Major depressive disorder ，簡稱MDD，重鬱症）影響全世界達10% 的人口，是全球生產力下滑的原因之一。然而市售超過40種的抗憂鬱劑，只有少於50%的患者能夠藉由藥物治療達到完全緩解，因此積極尋找替代療法極為重要。過去在功能性磁振造影（functional magnetic resonance imaging，簡稱 fMRI）的研究觀察到MDD病人在接受以情緒作為刺激的fMRI時，相對於控制組在左側背外側前額葉（dorsolateral prefrontal cortex，簡稱DLPFC）的活化較低且右側活化較高，推論DLPFC的活化不平衡與重鬱症的成因有關。根據過去研究，重覆性穿顱磁刺激（Repetitive transcranial magnetic stimulation，簡稱rTMS）近年來常用於治療重鬱症的前額葉活化不平衡，而陣發式穿顱磁刺激（Theta burst stimulation，簡稱TBS）較rTMS 有更長的後續作用時間，也開始廣泛被利用於許多不同疾病的治療上，然而在重鬱症上的治療效果仍待更多研究結果的證明。本研究我們利用TBS進行MDD的治療，觀察治療前後大腦的活化變化。研究中收集二十位MDD患者，以雙盲隨機試驗分配至TBS治療組和控制組，TBS治療組進行十次雙側TBS刺激，於左側DLPFC進行有促進神經活性效果之間斷性TBS （intermittent，iTBS），於右側DLPFC進行抑制效果之連續性TBS （continuous，cTBS），控制組則進行安慰性TBS刺激。兩組受試者皆在治療前後進行利用國際情緒圖片系統（International Affective Picture System，簡稱IAPS）引發不同情緒狀態之功能性磁振造影（functional magnetic resonance imaging scan，簡稱fMRI）掃描。研究結果顯示TBS治療能夠降低憂鬱症狀，而在fMRI的結果顯示兩組在左側額葉額上中迴（superior medial frontal gyrus，p=.005）與兩側視丘（thalamus，p=.005; p=.007）的血氧濃度相依訊號（Blood-oxygen-level dependent，BOLD）在治療後比起安慰性TBS治療組有顯著之活化上升；而在右側額葉中迴（middle frontal gyrus，p=.001）、前扣帶迴（anterior cingulate gyrus，p=.002）、楔前葉（precuneus，p=.004）與左側楔葉（cuneus，p=.004）的BOLD訊號在治療前後之在治療後差異比起安慰性TBS治療組有顯著降低，而在左側額葉額上中迴（superior medial frontal gyrus，p=.005）與兩側視丘（thalamus，p=.005; p=.007）則有顯著活化上升。藉由本研究我們了解TBS治療後能調節額葉的活化並顯著的改變與認知控制和情緒處理相關腦區的活化，並且是一種能夠替代抗憂鬱劑的有效療法，希望未來能普及化造福對於藥物治療效果不佳的重鬱症患者。 Major depressive disorder (MDD) affects 10% of the world population and is a leading cause of worldwide disability. Despite more than 40 antidepressants that are available, less than 50% of patients achieve full remission with medical treatment. Previous functional studies revealed that the imbalanced brain activities of bilateral dorsolateral prefrontal cortex (DLPFC) might play an important role in MDD. Their results showed the significant hypo- and hyper- activity at the left and the right DLPFC compared with healthy control. Based on these findings, transcranial magnetic stimulation (TMS) which could temporary change brain activity was then increasingly used in treating the MDD patients. Theta burst stimulation (TBS) is a new form of TMS which tended to produce a longer lasting effect on the brain. Although this method was now broadly used in all different kinds of applications, but in using of treating imbalanced brain of MDD was remain rare. In this study we focused on the brain activation changes and the treatment effect after TBS. Twenty patients were randomly assigned to the active TBS or the sham TBS group. Ten patients in active TBS group were treated with 10 sessions of bilateral TBS with facilitating intermittent TBS to the left DLPFC and inhibiting continuous TBS to the right DLPFC while the other ten patients underwent sham TBS treatment. Functional magnetic resonance imaging (fMRI) scan was performed both before and after TBS treatment. International Affective Picture System (IAPS) were used as stimulated materials to induce emotional changes during the scan. Results revealed that TBS treatment successfully reduced the severity of depression symptoms. Functional results of negative emotional test showed significant increased blood oxygen level dependent(BOLD) signal at the region of left superior medial frontal gyrus (p=.005) and bilateral thalamus(p=.005; p=.007) in active TBS group compared with the sham. Oppositely, regions at right middle frontal gyrus (p=.001), anterior cingulate gyrus (p=.002), precuneus (p=.004) and left cuneus (p=.004) showed significant decreased signal. In conclusion, we found TBS significantly reduce the severity of depression symptoms. The bilateral TBS simulation successfully modulated the frontal activity with regions related to cognitive control and emotional processing. These findings suggest that TBS is effective as a substituted strategy to antidepressant.
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