研究背景：穿顱磁刺激(Transcranial Magnetic stimulation，簡稱TMS )，可作為重鬱症治療的另一個選擇。運用陣發式穿顱磁刺激(Theta burst stimulation，簡稱TBS)，以Theta頻率刺激的方式將TMS刺激背側前額葉皮質(Dorsolateral prefrontal cortex，簡稱DLPFC)，有助於重鬱症的抗憂鬱效果，而DLPFC腦區具有整合認知與情緒調節的功能。 研究目的：TBS能有效治療重鬱症，本研究目的在於評估TBS治療後是否同時伴隨認知功能的變化，並且特別關注工作記憶。 研究方法：參與者為20位臨床重鬱症患者，採取雙盲、隨機對照分配到TBS治療組與假刺激組(Sham)。TBS治療組與假刺激組於治療前、治療後第1週、治療後第4週與後續追蹤第24週進行追蹤評估。另收27位為健康控制組，僅在治療前接受評估。TBS治療組接受10次TBS治療施打於左右半腦DLPFC；假刺激組接受與TBS治療組相同的程序，但並未實際導入磁刺激；健康控制組則不進行TBS程序。本研究採用N-Back作業作為測量工作記憶的工具，記憶負荷量操弄0、1、2等三個水準；並且施測21題式漢彌頓憂鬱量表(21-item Hamilton Rating Scale for Depression，簡稱HAMD-21)、貝克憂鬱量表第二版(Beck Depression Inventory II，簡稱BDI-II)、簡短式智能評估(Mini Mental State Examination，簡稱MMSE)與記憶廣度測驗(包含數字順序背誦測驗與數字逆序背誦測驗)。 結果：在HAMD-21的結果發現治療後第4週(p=.021)與後續追蹤第24週(p=.007)，TBS治療組的憂鬱分數顯著低於假刺激組。MMSE、記憶廣度測驗、數字順序背誦、數字逆序背誦與n-back的正確率結果發現，TBS治療組與假刺激組在四個時間點均沒有顯著差異。n-back的反應時間，0-back於治療後第1週(p=.050)與治療後第4週(p=.043)、1-back於治療後第4週(p=.048)與後續追蹤第24週(p=.002)、2-back於治療後第4週(p=.005)與後續追蹤第24週(p=.046)，均顯示TBS治療組的反應時間顯著快於假刺激組。 結論：相較於假刺激組，TBS治療組有效治療重鬱症，並且n-back工作記憶作業的反應時間顯著改善。藉由本研究我們了解運用TBS有助於重鬱症的抗憂鬱效果，同時伴隨工作記憶的改善，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。
Background: Repetitive transcranial magnetic stimulation (rTMS) on Dorsal Lateral Prefrontal Cortex (DLPFC) has been used increasingly as an alternative therapy for patients with major depressive disorder(MDD). Recently development of Theta-burst stimulation (TBS) requires less stimulation time and intensity to induce longer effects. Due to the DLPFC serve the functions to cognitive integration and emotional regulation, it is important to evaluate cognitive function while adopt TBS therapy on MDD patients. Purpose: This research aims to assess the cognitive function after TBS therapy in MDD patients with specially focus on working memory. Method: Twenty MDD patients recruited and were randomly assigned in sham-controlled trial with double-blinded control protocol. Participants in patient groups received 10-session bilateral active or sham TBS intervention on left and right DLPFC within week 1 to week 4. Twenty-Seven health adults recruited as age-matched control group. All groups of participants received a series of assessments and cognitive task at week 0, 1, 4, and 24. These assessments included the Mini Mental State Examination (MMSE), the 21-item Hamilton Rating Scale for Depression (HAMD-21), the Beck Depression Inventory II (BDI-II), and digit span test. The n-back task was adopted to evaluate participants’ working memory. Participants were asked to perform n-back with 0, 1, 2 levels of memory load manipulation.. Results & Discussions: The HAMD-21 scores of TBS-treated group were significantly decreased than TBS-sham group at week 4 (p=0.021) and week 24 (p=0.007). There were no significantly difference between TBS-treated group and TBS-sham group in MMSE, forward and backward digit memory tests. Results of n-back task shows that the reaction time of TBS-treated group were significantly shorter than TBS-sham group in 0-back at week 1 (p=0.05) and week 4 (p=0.043); in 1-back at week 4 (p=0.048) and week 24 (p=0.002); and in 2-back at week 4 (p=0.005) and week 24 (p=0.046). Conclusion: This randomized sham-controlled study demonstrated that active theta-burst stimulation produced good antidepressant efficacy. Furthermore, the reaction time of the n-back working memory task significantly improved along the TBS treatments. According to this study, TBS treatment not only improved the symptoms of MDD, but also improved the working memory reaction time.
