Guan Muzhen, Wang Zhongheng, Shi Yanru, Xie Yuanjun, Ma Zhujing, Liu Zirong, Liu Junchang, Gao Xinyu, Tan Qingrong, Wang Huaning
Department of Mental Health, Xi'an Medical University, Xi'an, China.
Deptartment of Psychiatry, Xijing Hospital, Air Force Medical University, Xi'an, China.
Front Neurosci. 2022 Mar 14;16:855483. doi: 10.3389/fnins.2022.855483. eCollection 2022.
Repetitive 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.
In this study, MDD patients with first-episode, drug-naive ( = 29) and healthy controls ( = 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).
Before treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus ( < 0.01), higher ALFF in the left middle frontal gyrus and left precuneus ( < 0.01), and lower ReHo in the left middle frontal and left middle occipital gyri ( < 0.01) than the values observed in healthy controls. After the rTMS treatment, the ALFF was significantly increased in the left superior frontal gyrus ( < 0.01) and decreased in the left middle frontal gyrus and left precuneus ( < 0.01). Furthermore, ReHo was significantly increased in the left middle frontal and left middle occipital gyri ( < 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 ( = -0.443, = 0.021).
rTMS 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.
This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019761).
重复经颅磁刺激（rTMS）可有效改善重度抑郁症（MDD）患者的抑郁症状；然而，其作用机制仍不清楚。本研究探讨rTMS改善MDD患者抑郁症状的神经影像学机制。
本研究纳入了首发、未服用过药物的MDD患者（n = 29）和健康对照者（n = 33）。使用汉密尔顿抑郁量表（HAMD - 17）评估rTMS治疗前后的抑郁症状。在治疗前后均收集静息态功能磁共振成像（rs - fMRI）数据。使用以下两个对评估自发神经元活动敏感的指标比较治疗后脑功能的变化：低频波动幅度（ALFF）和局部一致性（ReHo）。选择同步变化的脑区作为种子点，通过格兰杰因果分析（GCA）研究rTMS治疗前后种子点与全脑之间因果连接性的差异。
治疗前，MDD患者左侧额上回的ALFF显著降低（P < 0.01），左侧额中回和左侧楔前叶的ALFF较高（P < 0.01），左侧额中回和左侧枕中回的ReHo较低（P < 0.01），均低于健康对照者。rTMS治疗后，左侧额上回的ALFF显著增加（P < 0.01），左侧额中回和左侧楔前叶的ALFF降低（P < 0.01）。此外，MDD患者左侧额中回和左侧枕中回的ReHo显著增加（P < 0.01）。治疗前，以左侧额中回（同步变化的脑区）为种子点的GCA显示额中回与额上回之间存在较弱的双向因果连接，以及从颞下回到额中回的较弱因果连接。治疗后，这些因果连接得到加强。此外，从颞下回到额中回的因果连接与HAMD - 17总分呈负相关（r = -0.443，P = 0.021）。
rTMS治疗不仅改善了额中回、额上回和楔前叶的局部神经活动，还加强了额中回与额上回之间的双向因果连接以及从颞下回到额中回的因果连接。这些神经影像学指标的变化可能代表了rTMS治疗MDD的神经机制。
本研究在中国临床试验注册中心注册（注册号：ChiCTR1800019761）。
