Supplementary Material for: Clinical and Neurophysiological Effects of Robotically-Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Depression

Introduction: Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory major depressive disorder (MDD), but treatment outcomes vary substantially from person to person. Recent evidence suggests that incorporating neuroimaging-based targeting may help improve clinical outcomes. Here, we report the initial clinical outcomes of our open-label fMRI-personalized treatment protocol from the Queensland Neurostimulation Centre (QNC). Methods: This open-label, nonrandomized study was conducted between November 2021 and September 2024. Participants were a referred sample aged between 19 and 84, meeting the criteria for treatment-resistant MDD (N=61). They received 20 or 30-weekday sessions of DLPFC rTMS. The stimulation site was personalized using each individual’s fMRI brain connectivity data. Results: The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS). MADRS was lower post-treatment (d=1.78, p<.001), with 52% and 33% response and remission rates observed. Likewise, anxiety scores (Hamilton Anxiety Rating Scale) were lower post-treatment (d=1.27, p<.001), with 46% and 28% response and remission rates observed. The treatment was most effective in patients who qualified for randomized controlled trials (RCTs; N=19, MADRS response=74%, remission=53%) and least effective in patients with bipolar or neurological disorders (N=8, MADRS response=37%, remission=25%). Neurophysiologically, functional brain connectivity in the personalized DLPFC-SGC pathway was less anti-correlated post-treatment (d=0.63, p<.001). Conclusion: Our findings provide new clinical and neurophysiological evidence supporting the high effectiveness of fMRI-connectivity-guided personalized rTMS for MDD, especially in individuals without complex comorbidities. The results encourage future RCTs to assess the superiority of personalized targeting over standard TMS.引言：左侧背外侧前额叶皮层（dorsolateral prefrontal cortex, DLPFC）的重复性经颅磁刺激（repetitive transcranial magnetic stimulation, rTMS）是治疗难治性重度抑郁症（major depressive disorder, MDD）的成熟疗法，但不同患者的治疗效果存在显著个体差异。近期研究表明，结合基于神经影像的靶向定位策略或可改善临床疗效。本研究报告了昆士兰州神经刺激中心（Queensland Neurostimulation Centre, QNC）开展的开放标签功能磁共振成像（functional magnetic resonance imaging, fMRI）个性化治疗方案的初步临床结果。 方法：本项开放标签、非随机对照研究于2021年11月至2024年9月间开展。研究纳入61名年龄在19至84岁之间、符合难治性MDD诊断标准的转诊受试者。受试者接受为期20或30个工作日的DLPFC rTMS治疗，刺激位点基于个体的fMRI脑连接数据进行个性化定制。 结果：主要结局指标为蒙哥马利-阿斯伯格抑郁评定量表（Montgomery-Åsberg Depression Rating Scale, MADRS）评分变化。治疗后受试者MADRS评分显著降低（d=1.78, p<.001），应答率与缓解率分别为52%与33%。同样，汉密尔顿焦虑评定量表（Hamilton Anxiety Rating Scale）评分在治疗后也显著降低（d=1.27, p<.001），其应答率与缓解率分别为46%与28%。该疗法在符合随机对照试验（randomized controlled trial, RCT）纳入标准的受试者中疗效最佳（n=19，MADRS应答率74%，缓解率53%），而在合并双相情感障碍或神经系统疾病的受试者中疗效最差（n=8，MADRS应答率37%，缓解率25%）。神经生理学层面，个性化DLPFC-膝下扣带回皮层（subgenual cingulate cortex, SGC）通路的脑功能连接在治疗后负相关性显著减弱（d=0.63, p<.001）。 结论：本研究结果为基于fMRI连接引导的个性化rTMS治疗MDD的高有效性提供了新的临床与神经生理学证据，尤其适用于无复杂共病的患者。研究结果支持未来开展随机对照试验，以评估个性化靶向治疗相较于标准经颅磁刺激的优越性。