Personalized connectivity- and electric field-guided transcranial modulation of the subgenual anterior cingulate cortex in major depression

该项目的目的是进一步发展和个性化优化左背外侧前额叶皮质（DLPFC）重复经颅磁刺激（rTMS）治疗重度抑郁症。为此，我们首先开发了一种新的TMS线圈定位/定向优化方法，该方法基于DLPFC与亚属前扣带皮层（sgACC）之间连接的个体映射以及dpfc中TMS诱导电场的个体建模；建立并优化了一种个性化刺激强度的创新方法，该方法将tms诱发的运动皮层和DLPFC的电场与个体运动阈值进行比较。一项针对重度抑郁症患者的随机临床试验将研究我们的个体化连接和电场引导的左DLPFC rTMS的可行性、耐受性和有效性，并将其与最先进的rTMS治疗重度抑郁症进行比较。此外，使用TMS-fMRI同时测量，我们还将研究sgACC的激活和调节作为rTMS治疗的作用机制。在健康志愿者的进一步实验中，我们将使用连通性和电场引导(r)TMS和TMS- fmri同时测量，系统地研究TMS诱导的sgACC神经元激活和调节作为DLPFC-sgACC连通性和刺激强度的函数，以确定最有效激活和调节sgACC的最佳刺激参数。

The aim of the project is the further development and personalized optimization of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) for the treatment of major depression. To this end, we have firstly developed a new optimization method for the positioning/orientation of the TMS coil based on individual mapping of the connectivity between the DLPFC and the subgenual anterior cingulate cortex (sgACC) as well as individual modelling of the TMS-induced electric field in the DLPFC, and secondly, established and optimized an innovative method for individualization of the stimulation intensity which compares the TMS-induced electric fields in motor cortex and DLPFC with reference to the individual motor threshold. A pilot randomized clinical trial in patients with major depression will investigate the feasibility, tolerability and efficacy of our individualized connectivity- and electric field-guided rTMS of the left DLPFC and compare it with state-of-the-art rTMS treatments for major depression. In addition, using simultaneous TMS-fMRI measurements we will also investigate the role of activation and modulation of the sgACC as a mechanism of action of rTMS therapy. In further experiments in healthy volunteers, we will systematically investigate TMS-induced neuronal activation and modulation of the sgACC as a function of DLPFC-sgACC connectivity and stimulation intensity using connectivity- and electric field-guided (r)TMS and simultaneous TMS-fMRI measurements to determine optimal stimulation parameters for the most effective activation and modulation of the sgACC.