Multi-target repetitive Transcranial Magnetic Stimulation (rTMS) treatment for Major Depressive Disorder (MDD) and comorbid pain

项目摘要 重度抑郁症（MDD）和纤维肌痛（FM）是高度共病、致残和耐药的。 治疗超过一半的MDD患者存在疼痛症状，并且合并症与 生活质量降低、药物治疗结果差和阿片类药物使用障碍。的新办法 帮助共病患者是迫切需要的。重复经颅磁刺激（rTMS）治疗可能 改善疼痛和情绪症状，可能通过调节共同的潜在病理生理学 大脑网络 初步数据表明，应用于左背外侧前额叶皮层（IDLPFC）的rTMS显著改善了 抑郁和中度疼痛症状，但未能改善更严重的共病疼痛。在这 应用，我们建议测试多靶点rTMS方案的有效性，该方案可能更成功地治疗 MDD/FM共病患者的情绪和疼痛症状。这包括两个互补的目标：1）测试 一种新的rTMS方案对MDD和FM共病的影响，2）为患者提供关键的额外培训， 这将有助于她作为一名专门研究科摩罗问题的研究员向独立过渡。 慢性疼痛的情绪障碍及其rTMS治疗。这将通过随机、 采用两种实验条件的假对照研究：A）主动rTMS至IDLPFC（MDD的既定目标） 和对初级运动皮层（M1，确定的疼痛目标）的假rTMS;和B）对两者的主动rTMS，IDLPFC 还有M1。我们预计，多部位rTMS治疗MDD和FM症状将比 单点rTMS协议。此外，我们将确定神经签名的差异和相似之处， MDD和FM以及它们如何使用机器学习技术在共病条件下相互作用。 K 01项目将在加州大学洛杉矶分校进行，并得到神经调节主任的指导支持。 司，两个共同导师和其他四个合作者与专业知识的rTMS，抑郁症，慢性疼痛， 多模态成像和机器学习分析。这种方法将实现项目的具体目标：1。 评价多部位与单部位rTMS对临床症状的影响; 2.确定以下因素的相互作用 影响MDD和慢性疼痛的网络以及它们如何被rTMS调制;以及3.检查交互 rTMS的镇痛和抗抑郁作用之间的关系。如果这些目标得以实现， 该项目将有助于确定多部位rTMS对MDD和FM共病的疗效， MDD和FM的神经特征以及它如何被rTMS调制，并表征它们之间的关系。 rTMS诱导的抗抑郁和镇痛作用。从长远来看，目前的rTMS程序可能是 显著改善了MDD与慢性疼痛共病的治疗。

PROJECT SUMMARY Major Depressive Disorder (MDD) and fibromyalgia (FM) are highly comorbid, disabling and resistant to treatment. More than half of MDD patients present with pain symptoms, and the comorbidity is associated with reduced quality of life, poor pharmacological treatment outcomes, and opioid use disorders. New approaches to help comorbid patients are urgently needed. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment may ameliorate both pain and mood symptoms, possibly through modulation of shared underlying pathophysiological brain networks. Preliminary data indicate rTMS applied to the left dorsolateral prefrontal cortex (lDLPFC) significantly improved both depressive and moderate pain symptoms but failed to improve more severe comorbid pain. In this application, we propose to test the efficacy of a multi-target rTMS protocol that may be more successful in treating both mood and pain symptoms in comorbid MDD/FM. This includes two complementary objectives: 1) to test the effects of a novel rTMS protocol for comorbid MDD and FM, and 2) to provide critical additional training to the candidate that will facilitate her transition into independence as a researcher specializing in the comorbidity of mood disorders with chronic pain and their treatment with rTMS. This will be achieved through a randomized, sham-controlled study with two experimental conditions: A) Active rTMS to lDLPFC (established target for MDD) and sham rTMS to the primary motor cortex (M1, established pain target); and B) Active rTMS to both, lDLPFC and M1. We anticipate that multi-site rTMS will be more efficacious to treat both MDD and FM symptoms than the single site rTMS protocol. Additionally, we will determine the differences and similarities of neural signatures of MDD and FM and how these interact in the comorbid condition using machine learning techniques. The K01 project will take place at UCLA with the mentoring support from the director of the Neuromodulation Division, two co-mentors and four other collaborators with expertise in rTMS, depression, chronic pain, multimodal imaging, and machine learning analysis. This approach will achieve the project’s specific aims to: 1. Evaluate the effect of multi-site vs. single site rTMS on clinical symptoms; 2. Determine the interaction of networks affected in MDD and chronic pain and how they are modulated by rTMS; and 3. Examine the interaction between analgesic and antidepressant effects of rTMS. If these aims are achieved, the short-term outcome of this project will help determine the efficacy of multi-site rTMS for comorbid MDD and FM, identify the overlap of the neural signature of MDD and FM and how it is modulated by rTMS, and characterize the relationship between rTMS-induced antidepressant and analgesic effects. In the long-term, current rTMS procedures may be significantly improved for the treatment of MDD with comorbid chronic pain.