Effect of TMS on PTSD Neuroimaging and Psychophysiological Biomarkers

TMS 对 PTSD 神经影像和心理生理生物标志物的影响

• 批准号: 10054587
• 负责人: Sanne JH van Rooij
• 金额: $ 17.88万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10054587
• 关键词: African American; Aftercare; Amygdaloid structure; Biological; Biological Markers; Brain; Clinic; Clinical; Cognitive; Cues; Data; Data Analyses; Development; Disease; Distal; Dose; Down-Regulation; Dropout; Emotional; FDA approved; Financial Hardship; Foundations; Fright; Funding; Future; Galvanic Skin Response; Goals; Hippocampus (Brain); Hospitals; Impairment; Individual Differences; Infrastructure; Intervention; Low income; MRI Scans; Major Depressive Disorder; Measurable; Measures; Mental disorders; Mentors; Neurobiology; Neuronavigation; Neurosciences; Outcome; Outcome Measure; Patient Recruitments; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Phenotype; Physiologic pulse; Physiology; Placebos; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Primary Health Care; Protocols documentation; Psychiatric therapeutic procedure; Psychophysiology; Randomized; Recovery; Regulation; Research; Research Personnel; Resistance; Safety; Site; Startle Reaction; Stimulus; Structure; Symptoms; Testing; Therapeutic Effect; Time; Training; Transcranial magnetic stimulation; Trauma; Treatment Efficacy; Treatment outcome; United States; United States National Institutes of Health; Universities; Work; base; career; career development; clinical investigation; comorbidity; conditioned fear; experience; experimental study; functional disability; healthy volunteer; high risk; improved; interest; neural circuit; neurobiological mechanism; neuroimaging; neuroimaging marker; neuromechanism; neuroregulation; novel; personalized medicine; predicting response; predictive marker; programs; recruit; research study; response; study population; suicidal risk; trauma exposure; treatment duration; treatment response

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.

项目概要/摘要 K01提案的目的是使PI能够成为一名独立的研究调查员 局灶神经调节、临床研究、神经影像学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 NIH 资助的研究计划，通过了解来推进创伤相关疾病的治疗 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。这 拟议的研究利用了 PI 在受创伤人群的治疗前和治疗后研究中的经验， 创伤后应激障碍（PTSD）生物标志物研究，以及她在神经影像学和纵向数据分析方面的坚实基础。这 培训计划包括结构化指导、经颅磁刺激 (TMS) 实践培训和 大脑功能连接（FC）分析、教学课程和严格的拟议研究 提供以下方面的新培训：1) 局灶神经调节 (TMS)，2) 临床研究，3) FC 分析，以及 4) PTSD 生物标志物和 5) 职业发展方面的额外培训。 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， 由于缺乏对创伤后应激障碍 (PTSD) 恢复的神经机制的了解，阻碍了其发展。 TMS 对 PTSD 的研究已对 rDLPFC 施加 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。该 K01 提案旨在推进 TMS 对 PTSD 的治疗 通过更好地了解 TMS 的作用机制并检查 1Hz rDLPFC 刺激的效果 创伤后应激障碍 (PTSD) 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相关的生物标志物 与 PTSD 有关，并推测可通过 DLPFC 刺激得到改善。拟议的实验利用 格雷迪创伤项目 (GTP) 的基础设施是最大的民用 PTSD 研究，旨在为患者提供帮助 招募以及临床和生物学评估基金会。 PTSD 患者将被招募并随机分组 TMS（N = 30）或假治疗（N = 30）组。将收集神经影像和心理生理学数据 在两周治疗期（第 4 周）的前后一周。这个K01项目将做出重大贡献 通过以下方式促进 PTSD 治疗： 1) 确定对右侧 DLPFC 进行 1Hz TMS 是否可以改善 PTSD 中间表型； 2）为未来的研究提出新的大脑调节目标； 3）提供初步的 未来研究检查治疗反应个体差异的数据； 4）推进我们的 使用 TMS 作为探针了解 PTSD 治疗反应的神经生物学。