作为抑郁症治疗的重要补充方法，重复经颅磁刺激(rTMS)可能存在着与抗抑郁药物不同的生物学机制。我们前期的工作发现：持续存在的脑网络异常很可能是抑郁症反复发作的病理基础，而内源性大麻素（eCB）则是其背后的关键分子机制之一。rTMS可能在脑网络及eCB分子两个尺度上均有调节作用，进而产生抗抑郁作用。为验证上述假说，本课题拟从临床和基础实验两方面展开研究，首先使用神经影像学的方法观察抑郁症患者群体CB系统失衡情况与脑网络异常之间的相关性，并验证 rTMS 干预对上述病理改变的修复作用。进而以eCB基因敲除小鼠和细胞特异性 CB1R 基因敲除小鼠为研究平台，综合运用电生理、micro-MRI 技术和神经行为学等综合技术手段，验证 rTMS 对内源性大麻素的调节作用，系统阐明rTMS抗抑郁作用的生物学机制，为进一步优化rTMS治疗抑郁症提供理论基础，也可以为阐明抑郁症病因提供新的视角。

As the exploration of the current anti-depressive therapeutics, repetitive transcranial magnetic stimulation (rTMS) may elicit its antidepressive effect via the working mechanisms more than antidepressants. Our investigations have demonstrated the persistent injury of the brain network induced by the dysfunction of endogenous cannabinoids system (eCBs) maybe the pathological basis of the repeated episodes of MDD. Thus we hypothesized that rTMS induced the antidepressive effect through ameliorating the damaged brain network by the regulation of eCBs. To further verify this hypothesis, we will demonstrate the correlation between the damaged brain network and the deficit eCBs and whether rTMS attenuate this injury in MDD patients by functional MRI and PET. Moreover, we also use cell specific CB1R knockout mice, micro-MRI, electrophysiological and neurobehavioral methods to clarify the regulation of eCBs induced by rTMS. This study will explorethe anti-depressive mechanism of rTMS and supply more detail evidences to optimize the rTMS treatment.