Effect of TMS on PTSD Neuroimaging and Psychophysiological Biomarkers

项目总结/摘要 本K 01提案的目的是使PI成为独立的研究者， 在局灶性神经调节、临床研究、神经影像学和心理生理学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NIH资助的研究项目，通过了解创伤相关疾病的治疗方法， 治疗的神经生物学机制和识别治疗结果的预测生物标志物。的 拟议的研究利用了PI在创伤人群中进行治疗前和治疗后研究的经验， PTSD生物标志物研究，以及她在神经成像和纵向数据分析方面的坚实基础。的 培训计划包括结构化指导、经颅磁刺激（TMS）实践培训， 大脑功能连接（FC）分析，教学课程和严格的研究建议，以 提供以下方面的新培训：1）局灶性神经调节（TMS），2）临床研究，3）FC分析，以及 4）PTSD生物标志物和5）职业发展的额外培训。 由于30-50%的PTSD患者对一线治疗没有反应，因此需要新的治疗方法;然而， 由于缺乏对PTSD恢复的神经机制的理解，发展受到阻碍。 经颅磁刺激（TMS）在创伤后应激障碍（PTSD）中的研究已经在rDLPFC上应用了1Hz刺激，并证明了一种潜在的治疗方法 但TMS的作用机制尚不清楚。K 01提案旨在推进TMS治疗PTSD 通过更好地理解TMS的作用机制和检查1Hz rDLPFC刺激的效果， 创伤后应激障碍神经影像学和心理生理学生物标志物，特别是与恐惧神经回路有关的， 与创伤后应激障碍有关，并假设通过DLPFC刺激得到改善。拟议的实验利用 格雷迪创伤项目（GTP）的基础设施，最大的民间创伤后应激障碍研究，为病人 招募和临床和生物评估基金会。PTSD患者将被招募并随机分配 TMS组（N=30）和假手术组（N=30）。将收集神经影像学和心理生理学数据 在两周治疗期（第4周）之前和之后的一周。K 01项目将大大有助于 通过以下方式促进PTSD治疗：1）确定右侧DLPFC的1Hz TMS是否改善PTSD 中间表型; 2）为未来的研究提出新的脑调节靶点; 3）提供初步的 未来研究的数据，检查治疗反应的个体差异;以及4）推进我们的 使用TMS作为探针来理解PTSD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.