Department of Imaging, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Hum Brain Mapp. 2018 Nov;39(11):4580-4592. doi: 10.1002/hbm.24307. Epub 2018 Aug 29.
Major depressive disorder (MDD) is a severe mental disorder associated with high morbidity and mortality rates, which remains difficult to treat, as both resistance and recurrence rates are high. Repetitive transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) provides a safe and effective treatment for selected patients with treatment-resistant MDD. Little is known about the mechanisms of action of TMS provided to the left DLPFC in MDD and we can currently not predict who will respond to this type of treatment, precluding effective patient selection. In order to shed some light on the mechanism of action, we applied single pulse TMS to the left DLPFC in 10 healthy participants using a unique TMS-fMRI set-up, in which we could record the direct effects of TMS. Stimulation of the DLPFC triggered activity in a number of connected brain regions, including the subgenual anterior cingulate cortex (sgACC) in four out of nine participants. The sgACC is of particular interest, because normalization of activity in this region has been associated with relief of depressive symptoms in MDD patients. This is the first direct evidence that TMS pulses delivered to the DLPFC can propagate to the sgACC. The propagation of TMS-induced activity from the DLPFC to sgACC may be an accurate biomarker for rTMS efficacy. Further research is required to determine whether this method can contribute to the selection of patients with treatment resistant MDD who will respond to rTMS treatment.
重度抑郁症（MDD）是一种严重的精神障碍，与高发病率和死亡率相关，其治疗仍然具有挑战性，因为耐药和复发率都很高。左背外侧前额叶皮层（DLPFC）的重复经颅磁刺激（rTMS）为治疗耐药性 MDD 的选定患者提供了一种安全有效的治疗方法。对于 rTMS 作用于 MDD 左 DLPFC 的机制知之甚少，我们目前无法预测谁会对这种治疗有反应，从而无法有效地选择患者。为了阐明作用机制，我们在 10 名健康参与者中使用独特的 TMS-fMRI 装置对左 DLPFC 进行了单次脉冲 TMS，在该装置中我们可以记录 TMS 的直接作用。刺激 DLPFC 引发了多个连接的脑区的活动，包括九名参与者中的四名的前扣带回皮质亚区（sgACC）。sgACC 特别有趣，因为该区域的活动正常与 MDD 患者抑郁症状的缓解有关。这是 TMS 脉冲传递到 DLPFC 可以传播到 sgACC 的直接证据。从 DLPFC 到 sgACC 的 TMS 诱导活动的传播可能是 rTMS 疗效的准确生物标志物。需要进一步研究以确定该方法是否可以帮助选择对 rTMS 治疗有反应的治疗耐药性 MDD 患者。
