Effect of TMS on PTSD Neuroimaging and Psychophysiological Biomarkers

项目摘要/摘要 这项K01提案的目的是使PI成为独立的研究调查员， 在局部神经调节、临床研究、神经成像和心理生理生物标志物方面的专业知识 对受创伤人群和创伤后应激障碍(PTSD)的研究。候选人的长期目标 是建立一个由美国国立卫生研究院资助的研究项目，通过了解 治疗的神经生物学机制和确定预测治疗结果的生物标志物。这个 拟议的研究利用了PI在创伤人群治疗前和治疗后研究的经验， 她从事创伤后应激障碍生物标记物研究，并在神经影像和纵向数据分析方面拥有深厚的基础。这个 培训计划包括结构化指导、经颅磁刺激(TMS)实践培训和 大脑功能连通性(FC)分析、教学课程和严格的拟议研究 提供1)局灶性神经调节(TMS)，2)临床研究，3)FC分析，以及 4)创伤后应激障碍生物标志物的额外培训，以及5)职业发展。 由于30%-50%的创伤后应激障碍患者对一线治疗没有反应，新的治疗方法是有必要的；然而， 由于缺乏对创伤后应激障碍康复的神经机制的了解，发育受到阻碍。 创伤后应激障碍的TMS研究已经在rDLPFC上应用了1赫兹的刺激，并展示了一种潜在的治疗方法 但TMS的作用机制尚不清楚。这份K01提案旨在推进创伤后应激障碍的TMS治疗 通过更好地了解TMS的作用机制和检测1 HzrDLPFC刺激的效果 关于创伤后应激障碍的神经成像和心理生理生物标记物，特别是与恐惧相关的神经回路 与创伤后应激障碍有关，并被认为可以通过刺激DLPFC得到改善。拟议中的实验利用 最大的民间创伤后应激障碍研究项目(GTP)的基础设施，为患者 招募和临床及生物学评估基金会。创伤后应激障碍患者将被招募并随机分配 TMS组(N=30)或假治疗组(N=30)。将收集神经成像和心理生理学数据 在两周治疗前后的一周(第4周)。这个K01项目将对 通过：1)确定右侧DLPFC的1赫兹TMS是否改善了创伤后应激障碍 中间表型；2)为未来的研究提供新的大脑调节靶点；3)提供初步的 为未来的研究提供数据，以检查治疗反应的个体差异；以及4)推进我们的 以TMS为探针了解创伤后应激障碍治疗反应的神经生物学。

Project Summary/Abstract The purpose of this K01 proposal is to enable the PI to become an independent research investigator with expertise in focal neuromodulation, clinical investigations, and neuroimaging and psychophysiological biomarker research in traumatized populations and post-traumatic stress disorder (PTSD). The candidate's long-term goal is to build a NIH-funded research program to advance treatment for trauma-related disorders by understanding the neurobiological mechanisms of treatment and identifying predictive biomarkers for treatment outcome. The proposed study leverages the PI's experience with pre- and post-treatment studies in traumatized populations, PTSD biomarker research, and her strong foundation in neuroimaging and longitudinal data analyses. The training plan includes structured mentoring, hands-on training in Transcranial Magnetic Stimulation (TMS) and brain functional connectivity (FC) analyses, didactic coursework and a rigorous proposed research study in order to provide new training in 1) focal neuromodulation (TMS), 2) clinical investigations, 3) FC analyses, and additional training in 4) PTSD biomarkers, and 5) career development. With 30-50% of PTSD patients not responding to first line therapies, novel treatments are warranted; however, development is hampered by a lack of understanding of neural mechanisms underlying recovery from PTSD. TMS studies in PTSD have applied 1Hz stimulation over the rDLPFC and demonstrated a potential therapeutic effect, but the mechanism of TMS remains unclear. This K01 proposal aims to advance TMS treatment for PTSD by better understanding the mechanism of action of TMS and examining the effect of 1Hz rDLPFC stimulation on PTSD neuroimaging and psychophysiological biomarkers, particularly related to the fear neurocircuitry often implicated in PTSD and hypothesized to be improved by DLPFC stimulation. The proposed experiments leverage the infrastructure of the Grady Trauma Project (GTP), the largest civilian PTSD research study, for patient recruitment and clinical and biological assessment foundation. PTSD patients will be recruited and randomized to a TMS (N=30) or sham treatment (N=30) group. Neuroimaging and psychophysiological data will be collected in the week before and after the two-week treatment period (week 4). This K01 project will significantly contribute to the advancement of treatment for PTSD by: 1) determining if 1Hz TMS to the right DLPFC improves PTSD intermediate phenotypes; 2) suggesting novel brain modulation targets for future studies; 3) providing preliminary data for future studies examining individual differences for treatment response; and 4) advancing our understanding of neurobiology of PTSD treatment response using TMS as a probe.