ObjectiveRepetitive transcranial magnetic stimulation (rTMS) can effectively improve depression symptoms in patients with major depressive disorder (MDD); however, its mechanism of action remains obscure. This study explored the neuralimaging mechanisms of rTMS in improving depression symptoms in patients with MDD.MethodsIn this study, MDD patients with first-episode, drug-naive (n = 29) and healthy controls (n = 33) were enrolled. Depression symptoms before and after rTMS treatment were assessed using the Hamilton Depression Rating Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected both before and after the treatment. Changes in the brain function after the treatment were compared using the following two indices: the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), which are sensitive for evaluating spontaneous neuronal activity. The brain region with synchronous changes was selected as the seed point, and the differences in the causal connectivity between the seed point and whole brain before and after rTMS treatment were investigated via Granger causality analysis (GCA).ResultsBefore treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus (p < 0.01), higher ALFF in the left middle frontal gyrus and left precuneus (p < 0.01), and lower ReHo in the left middle frontal and left middle occipital gyri (p < 0.01) than the values observed in healthy controls. After the rTMS treatment, the ALFF was significantly increased in the left superior frontal gyrus (p < 0.01) and decreased in the left middle frontal gyrus and left precuneus (p < 0.01). Furthermore, ReHo was significantly increased in the left middle frontal and left middle occipital gyri (p < 0.01) in patients with MDD. Before treatment, GCA using the left middle frontal gyrus (the brain region with synchronous changes) as the seed point revealed a weak bidirectional causal connectivity between the middle and superior frontal gyri as well as a weak causal connectivity from the inferior temporal to the middle frontal gyri. After treatment, these causal connectivities were strengthened. Moreover, the causal connectivity from the inferior temporal gyrus to the middle frontal gyri negatively correlated with the total HAMD-17 score (r = −0.443, p = 0.021).ConclusionrTMS treatment not only improves the local neural activity in the middle frontal gyrus, superior frontal gyrus, and precuneus but also strengthens the bidirectional causal connectivity between the middle and superior frontal gyri and the causal connectivity from the inferior temporal to the middle frontal gyri. Changes in these neuroimaging indices may represent the neural mechanisms underlying rTMS treatment in MDD.Clinical Trial RegistrationThis study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019761).

Objective:This study explored the impacts of repetitive transcranial magnetic stimulation (rTMS) on spontaneous brain activity in patients with major depressive disorder (MDD).Methods:This study was a randomized controlled study. First-episode, drug-na?ve patients with MDD ( n=27) and healthy controls ( n=30) were enrolled. The left dorsolateral prefrontal region was the stimulation target, and all participants received rTMS treatment for fifteen successive days. Hamilton Depression Rating Scale (HAMD 17) and resting-state functional magnetic resonance imaging (rs-fMRI) data were collected at baseline and the 15th day of the treatment. Changes in the spontaneous brain activity before and after the treatment were compared using the paired samples t-test or the independent sample t-test. The two indices of the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity(ReHo) were applied to reflect the spontaneous brain activity. Results:After treatment, the score of HAMD 17 (9.4±4.3) in MDD patients was significantly lower than that before the treatment (21.1±6.0), the average score decreased by (11.7±3.6), the remission rate was 40.74%, and the response rate was 74.07%. fMRI results: Before treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus ( t=-8.14, P<0.001), higher ALFF in the left middle frontal gyrus and left precuneus ( t=5.79, 6.24, P<0.001), and lower ReHo in the left middle frontal and left middle occipital gyri ( t=-5.17, -6.11, P<0.001) than the corresponding values observed in healthy controls; After the rTMS treatment, the ALFF significantly increased in the left superior frontal gyrus ( t=7.32, P<0.001) and decreased in the left middle frontal gyrus and left precuneus ( t=-4.96,-5.14, P<0.001). Furthermore, ReHo significantly increased in the left middle frontal and left middle occipital gyri ( t=4.25,4.19, P<0.001) in patients with MDD. The score of HAMD 17 after treatment was significantly and negatively correlated with ALFF value of left superior frontal gyrus after treatment ( r=-0.390, P=0.044). Conclusion:Successive 15-day rTMS treatment could efficiently and effectively alleviate individual′s depressive symptoms. The left middle frontal gyrus may play an important role in abnormal spontaneous brain activity in MDD patients; and left superior frontal gyrus function may be essential in improving depressive symptoms.

目的 采集静息态功能磁共振(fMRI)数据,通过分析低频振幅(ALFF)指标考察首发抑郁症患者在重复经颅磁刺激(rTMS)治疗前后的脑功能活动变化,初步探讨rTMS治疗对抑郁症患者潜在的神经作用机制.方法 选取2019年5月至2020年12月在空军军医大学第一附属医院心身科就诊的35例首发抑郁症患者作为治疗组,通过广告招募纳入与治疗组性别、年龄、教育年限相匹配的37名健康人作为对照组.两组均行静息态fMRI扫描.治疗组在完成15 d的rTMS治疗后再次行fMRI扫描,同时对两组进行临床量表评估.通过DPABI软件对fMRI数据进行处理,计算两组被试全脑的ALFF值并进行比较分析.结果 治疗组患者在rTMS治疗后的汉密尔顿抑郁量表[22.00(20.25,24.00)分比10.00(8.00,11.75)分,U=40.50]、广泛性焦虑量表[8.50(6.00,11.00)分比6.00(4.25,7.00)分,U=234.00]和患者健康问卷抑郁症状群量表[14.50(12.00,19.00)分比9.00(6.00,11.75)分,U=138.50]得分均显著降低,差异有统计学意义(P<0.001).与治疗前相比,抑郁症患者在rTMS治疗后右侧额上回[-1.02(-1.08,-0.67)比-0.68(-0.99,-0.29),U=217.00,P=0.007]和右侧颞下回[-0.50(-0.67,-0.33)比-0.29(-0.41,-0.08),U=173.00,P<0.01]的ALFF升高,右侧缘上回[0.89(0.46,1.13)比0.36(0.06,0.81),U=228.00,P=0.012]和左侧后扣带回[1.09(0.81,1.39)比0.69(0.05,1.00),U=198.00,P=0.002]的ALFF降低.事后比较结果显示,经过rTMS治疗后,抑郁症这些脑区的ALFF值与健康对照组比较差异无统计学意义(P>0.05),表明在rTMS治疗后,这些功能异常的脑区趋于正常或逆转.结论 rTMS治疗可以增强额上回和颞下回的神经活动水平,而降低缘上回和后扣带回等脑区的神经活动强度,对抑郁症患者的脑功能活动具有动态调节作用.

目的 探讨枕叶重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)联合草酸艾司西酞普兰片对首发且未用药抑郁症患者认知功能的改善.方法 选取2019年1-12月首发未用药住院抑郁症患者,随机分为枕叶rTMS真刺激组22例,伪刺激组18例,两组均服用草酸艾司西酞普兰片,每日药物剂量差异无统计学意义(P>0.05).采用汉密尔顿抑郁量表(Hamilton depression rating scale,HAMD)评估治疗前后抑郁症状;采用N2、P3a和P3b评估治疗前后认知功能的改善.结果 两组治疗20 d后HAMD总分均显著低于治疗前(14.851±3.694 vs20.062±4.143,F1,38=346.279,P<0.001);治疗后,真刺激组的P3a的潜伏期显著低于伪刺激组[(304.571±56.330)ms vs(321.396±45.569)ms,P<0.05];治疗后,真刺激组P3b的潜伏期显著低于伪刺激组[(359.818±47.544)ms vs(393.333±48.340)ms,P<0.001].结论 枕叶rTMS治疗,能增强抑郁症患者早期疗效,有效改善认知加工的速度,为临床抑郁症患者rTMS治疗新靶点提供科学依据.