He Hengda, Sun Xiaoxiao, Doose Jayce, Faller Josef, McIntosh James R, Saber Golbarg T, Huffman Sarah, Hong Linbi, Pantazatos Spiro P, Yuan Han, McTeague Lisa M, Goldman Robin I, Brown Truman R, George Mark S, Sajda Paul
Department of Biomedical Engineering, Columbia University, New York, 10027, NY, USA.
Center for Biomedical Imaging, Medical University of South Carolina, Charleston, 29425, SC, USA.
medRxiv. 2024 Dec 27:2024.12.24.24319609. doi: 10.1101/2024.12.24.24319609.
Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is an established intervention for treatment-resistant depression (TRD), yet the underlying therapeutic mechanisms remain not fully understood. This study employs an integrative approach that combines TMS with concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), aimed at assessing the acute/immediate effects of TMS on brain network dynamics and their correlation with clinical outcomes. Our study demonstrates that TMS acutely modulates connectivity within vital brain circuits, particularly the cognitive control and default mode networks. We found that the baseline TMS-evoked responses in the cognitive control and limbic networks significantly predicted clinical improvement in patients receiving a novel EEG-synchronized repetitive TMS treatment. Furthermore, this study explored the brain-state dependent effects of TMS, as the brain-state indexed by the phase of EEG prefrontal alpha oscillation. We found that clinical outcomes in this novel treatment are linked to state-specific TMS-modulated functional connectivity within a pivotal brain circuit of the L-DLPFC and the posterior subgenual anterior cingulate cortex within the limbic system. These findings contribute to our understanding of the therapeutic effects underlying TMS treatment in depression and support the potential of assessing state-dependent TMS effects in TMS timing target selection. This study emphasizes the importance of personalized timing of TMS for optimizing target engagement of specific clinically relevant brain circuits. Our results are crucial for future research into the development of personalized neuromodulation therapies for TRD patients.
经颅磁刺激（TMS）作用于左侧背外侧前额叶皮质（L-DLPFC）是一种针对难治性抑郁症（TRD）的既定干预措施，但其潜在的治疗机制仍未完全明确。本研究采用了一种综合方法，将TMS与同步功能磁共振成像（fMRI）和脑电图（EEG）相结合，旨在评估TMS对脑网络动力学的急性/即时影响及其与临床结果的相关性。我们的研究表明，TMS能急性调节重要脑回路内的连通性，尤其是认知控制和默认模式网络。我们发现，在接受新型脑电图同步重复TMS治疗的患者中，认知控制和边缘系统网络中TMS诱发的基线反应显著预测了临床改善情况。此外，本研究还探讨了TMS的脑状态依赖性效应，即由脑电图前额叶α振荡相位所索引的脑状态。我们发现，这种新型治疗中的临床结果与L-DLPFC关键脑回路以及边缘系统内膝下前扣带回后部皮质内特定状态下TMS调节的功能连通性有关。这些发现有助于我们理解TMS治疗抑郁症的潜在治疗效果，并支持在TMS时机靶点选择中评估状态依赖性TMS效应的潜力。本研究强调了TMS个性化时机对于优化特定临床相关脑回路的靶点参与的重要性。我们的结果对于未来针对TRD患者开发个性化神经调节疗法的研究至关重要。
