使用基于fMRI的靶向方法对抑郁症进行个体化的rTMS治疗
Summary
本方案描述了重复经颅磁刺激（rTMS）的应用，其中背外侧前额叶皮层（DLPFC）的一个子区域与亚属前扣带皮层（sgACC）具有最强的功能反相关，位于基于fMRI的神经导航系统的辅助下作为刺激靶标。
Abstract
为了获得更大的临床疗效，重度抑郁症（MDD）的治疗革命备受期待。重复性经颅磁刺激（rTMS）是一种非侵入性和安全的神经调节技术，可立即改变大脑活动。尽管在MDD的治疗中应用广泛，但治疗反应在个体之间仍然不同，这可能是由于刺激靶点的定位不准确。我们的研究旨在研究功能性磁共振成像（fMRI）辅助定位是否能提高rTMS治疗抑郁症的疗效。我们打算鉴定和刺激MDD中背外侧前额叶皮层（DLPFC）的分区域，该分区域与亚属前扣带皮层（sgACC）具有最强的抗相关性，并对这种新方法和传统的5-cm规则进行比较研究。为了实现更精确的刺激，在神经导航系统的指导下应用了这两种方法。我们预计，基于静息状态功能连接的个体化定位TMS治疗可能比5-cm方法显示出更好的临床疗效。
Introduction
重性抑郁障碍（MDD）的特征是显着和持续的抑郁症，在更严重的情况下，患者可能会遇到幻觉和/或妄想1，2。与一般人群相比，MDD患者的自杀风险高出约20倍3。虽然药物是目前最常用的MDD治疗方法，但30%-50%的患者缺乏对抗抑郁药的充分反应4。对于应答者来说，症状改善往往在相对较长的潜伏期后出现，并伴有副作用。心理治疗虽然对某些患者有效，但成本高昂且耗时。因此，迫切需要更安全、更有效的MDD治疗。
重复经颅磁刺激（rTMS）是一种非侵入性和安全的技术，已被批准用于治疗各种精神障碍5，6，7。尽管其治疗机制尚不清楚，但据推测，rTMS通过调节受刺激大脑区域的活动和神经可塑性8，9，10起作用，从而使特定的功能网络10，11，12正常化。rTMS还引起网络效应，其通过连接途径唤起远程大脑区域的变化，导致放大的治疗效果13。虽然rTMS可以立即而有力地改变大脑活动，但其在MDD治疗中的反应率仅为18%左右14。主要原因可能是刺激目标15的位置不准确。
亚属前扣带皮层（sgACC）主要负责情绪处理，并在调节对压力事件的反应，对内部和外部刺激的情绪反应以及情绪表达中发挥作用16，17，18。ACC的这个次区域与大脑皮层和边缘系统共享大量的结构和功能连接19，20。有趣的是，研究表明，该区域的刺激后活动与TMS的临床疗效密切相关。例如，在针对右背外侧前额叶皮层（DLPFC）的TMS疗程后，sgACC的血流量减少，这与缓解抑郁症状有关21。Vink等人发现靶 向DLPFC的刺激被传播到sgACC，并提出sgACC活性可以是TMS治疗反应的生物标志物。根据之前的研究，Fox及其同事22提出，靶向DLPFC的一个次区域，该次区域与sgACC（MNI坐标：6，16，-10）显示出最强的功能抗连通性，可以增强抗抑郁作用。在这里，我们展示了一个旨在检验这一假设的研究方案。
Protocol
告知所有参与者有关研究的信息，并要求他们在研究开始前签署知情同意书。本方案经广州医科大学附属脑医院研究伦理委员会批准。 注意：在这项双盲研究中，抑郁症患者被随机分为两组。在实验组中，刺激目标通过基于DLPFC-sgACC的个性化定位方法定位（详见3.3）。对照组的目标通过平均5-cm方法获得（即（-41，16，54））22。 1. 参与者?…
Representative Results
ROI方面的FC分析应该表明，sgACC与DLPFC具有显着的反相关性，其中最强的负相关是要选择的刺激目标。sgACC-DLPFC功能连接性与治疗反应之间的显著反相关性应在相关性分析33中找到。 目前的方案基于一种创新的TMS靶向方法，以前没有研究应用过。在这里，我们介绍一项应用传统5厘米方法的fMRI指导TMS试验的结果。该研究34 提出了一种新的治疗?…
Discussion
sgACC负责情绪处理，并在压力调节16，17，18中发挥重要作用。一项研究表明，靶向与sgACC（6，16，-10）表现出最强功能抗连通性的DLPFC次区域可以增强抗抑郁作用25。因此，精确定位此目标是该协议的关键步骤。在刺激之前，应在神经导航的帮助下准确标出大脑的边界，并仔细记录头部以确保头部模型的准确性?…
Divulgations
The authors have nothing to disclose.
Acknowledgements
本研究由中国博士后科学基金资助项目（2019M652854）和中国广东省自然科学基金（批准号：2020A1515010077）资助。
Materials
| 3T Philips Achieva MRI scanner | Philips | ||
| Harvard/Oxford cortical template | http://www.cma.mgh.harva rd.edu/ | ||
| MATLAB | MathWorks | ||
| SPM12 | http://www.fil.ion.ucl.ac.uk/spm | ||
| The Visor2 system | ANT Neuro | The Visor2 software, the optical tracking system, tracking tools and calibration board are part of the visor2 system. | |
| TMS device | Magstim, Carmarthenshire, UK |
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Citer Cet Article
Luo, X., Hu, Y., Wang, R., Zhang, M., Zhong, X., Zhang, B. Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method. J. Vis. Exp. (174), e62687, doi:10.3791/62687 (2021).