Department of Psychiatry and Brain and Mind Research Institute, Weill Cornell Medicine, New York (Elbau, Lynch, Power, Solomonov, Liston); Department of Psychiatry and Institute of Medical Science, Faculty of Medicine, University of Toronto, and Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto (Downar, Blumberger); Non-Invasive Neurostimulation Therapies Lab and Department of Psychiatry, University of British Columbia, Vancouver (Vila-Rodriguez); Department of Psychiatry, University of California, San Diego (Daskalakis).
Am J Psychiatry. 2023 Mar 1;180(3):230-240. doi: 10.1176/appi.ajp.20220306.
Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the effect of the stimulation site's functional connectivity with the sgACC (sgACC-StimFC) on treatment outcome to rTMS in 295 patients with major depression.
The reliability and accuracy of estimating sgACC functional connectivity were validated with data from individuals who underwent extensive functional MRI testing. Electric field modeling was used to analyze associations between sgACC-StimFC and clinical improvement using standardized assessments and to evaluate sources of heterogeneity.
An imputation-based method provided reliable and accurate sgACC functional connectivity estimates. Treatment responses weakly but robustly correlated with sgACC-StimFC (r=-0.16), but only when the stimulated cortex was identified using electric field modeling. Surprisingly, this association was driven by patients with strong global signal fluctuations stemming from a specific periodic respiratory pattern (r=-0.49).
Functional connectivity between the sgACC and the stimulated cortex was correlated with individual differences in treatment outcomes, but the association was weaker than those observed in previous studies and was accentuated in a subgroup of patients with distinct, respiration-related signal patterns in their scans. These findings indicate that in a large representative sample of patients with major depressive disorder, individual differences in sgACC-StimFC explained only ∼3% of the variance in outcomes, which may limit the utility of existing sgACC-based targeting protocols. However, these data also provide strong evidence for a true-albeit small-effect and highlight opportunities for incorporating additional functional connectivity measures to generate models of rTMS response with enhanced predictive power.
重复经颅磁刺激（rTMS）方案越来越多地使用扣带回前下皮质（sgACC）的功能连接来个体化治疗靶点。然而，这种方法的疗效尚不清楚，不同研究之间存在相互矛盾的结果和不同的效应大小。在这里，作者研究了刺激部位与 sgACC 的功能连接（sgACC-StimFC）对 295 例重度抑郁症患者接受 rTMS 治疗的疗效的影响。
通过对接受广泛功能磁共振成像测试的个体的数据进行验证，确定了估计 sgACC 功能连接的可靠性和准确性。使用电场建模分析了 sgACC-StimFC 与临床改善之间的关联，使用标准化评估进行分析，并评估了异质性的来源。
基于插补的方法提供了可靠和准确的 sgACC 功能连接估计。治疗反应与 sgACC-StimFC 呈弱但稳健的相关性（r=-0.16），但仅当使用电场建模识别刺激皮层时才会出现这种相关性。令人惊讶的是，这种相关性是由源自特定周期性呼吸模式的强烈全局信号波动的患者驱动的（r=-0.49）。
sgACC 与刺激皮层之间的功能连接与治疗结果的个体差异相关，但这种相关性比以前的研究观察到的要弱，并且在扫描中存在特定呼吸相关信号模式的患者亚组中更为明显。这些发现表明，在一个大型的、有代表性的重度抑郁症患者样本中，sgACC-StimFC 的个体差异仅解释了结果中约 3%的差异，这可能限制了现有基于 sgACC 的靶向方案的实用性。然而，这些数据也为真实存在的、尽管效果较小的效应提供了强有力的证据，并突出了结合其他功能连接测量的机会，以生成具有增强预测能力的 rTMS 反应模型。
