BACKGROUND Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. METHODS Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. RESULTS More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. CONCLUSIONS These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders.

中文翻译：

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创伤后应激障碍和重性抑郁障碍对经颅磁刺激临床反应的网络机制

背景重复经颅磁刺激（TMS）疗法可以调节重度抑郁症（MDD）的病理性神经网络功能连接。创伤后应激障碍通常与 MDD 并存，TMS 治疗可以缓解这两种疾病的症状。这是第一项评估创伤后应激障碍和 MDD 合并症患者 TMS 相关连接变化的研究。方法 在一项前瞻性开放试验中，对 33 名成人门诊患者在 TMS 治疗前后获得静息状态功能连接磁共振成像。每天最多 40 次，将 5 Hz 的 TMS 传送到左侧背外侧前额叶皮层。分析使用了与 TMS、创伤后应激障碍或 MDD（膝下前扣带皮层 [sgACC]、左背外侧前额叶皮层、海马体和基底外侧杏仁核）以确定反应的成像预测因子并评估 TMS 后连接的临床相关变化，然后进行留一法交叉验证。使用数据驱动的多体素模式激活探索成像结果。结果 sgACC 和默认模式网络之间更负的预处理连接预测了临床改善，杏仁核到腹内侧前额叶皮层的连接更积极。TMS 后，症状减轻与 sgACC 与默认模式网络、左背外侧前额叶皮层和脑岛之间的连接性降低以及海马体与显着性网络之间的连接性降低有关。多体素模式激活证实了基于种子的预测因子和治疗结果的相关性。结论 这些结果突出了 sgACC、默认模式网络和显着性网络作为 TMS 反应预测因子的核心作用，并表明它们参与了作用机制。此外，这项工作表明，可能存在与这些常见共病疾病相关的基于网络的临床反应生物标志物。