Neural Correlates of Location-Specific Contextual Threat Discrimination in Post-Traumatic Stress Disorders

创伤后应激障碍(PTSD)是一种非常普遍的、使人衰弱的疾病。尽管做出了努力 关于创伤后应激障碍的病理生理特征，目前还没有建立可测量的指标来帮助诊断， 治疗进展，以及治疗反应的预测。这个K01介绍了一个研究和 支持申请人成为独立调查员的培训，重点是 使用位置特异性的环境中学习价差的潜在神经机制 通过跨学科的方法提供信息。培训计划建立在候选人之前的培训基础上，并且 经验和利用导师团队和研究环境，以促进 应聘者在1)了解与创伤后应激障碍相关的神经和心理生理学特征方面的专业知识，2) 更深入地精通多模式磁共振成像(MRI)数据采集和分析，3) 对精神障碍症状学、诊断和患者相关研究方面的专业知识的理解，以及 (4)负责任的科研行为。这项研究项目将使用一种新颖的虚拟现实任务，创建 由申请人在健康人身上验证，以评估患有脑部疾病的患者之间的脑活动差异 创伤后应激障碍(PTSD)组(n=30)，创伤暴露健康对照组(TEHC，n=30)，无创伤暴露健康对照组(HC， N=30)。将使用多模式MRI方法(功能、静息状态和结构MRI)，旨在阐明 创伤后应激障碍背景威胁辨别的神经机制。此外，功能磁共振成像将与 焦虑的外周测量(例如，皮肤电导反应、心率、呼吸、斜视测量)，主观 焦虑程度和创伤后应激障碍的症状群。这项研究将在哥伦比亚医学中心进行， 由于焦虑障碍诊所的最佳位置，可以在创伤后应激障碍研究范围内接触到创伤后应激障碍患者 计划和成像设施。拟议的研究结果将对澄清 对患有焦虑症和创伤后应激障碍患者的背景威胁的辨别，并将导致未来的R01 审查焦虑和创伤相关障碍的其他威胁相关学习过程的拨款。一起， 通过K01奖项开发的研究和培训经验和专业知识将支持 申请人向研究独立的过渡，并确保申请人成为研究领域的领先权威 环境中威胁学习和辨别所需的大脑区域的具体作用以及它们是如何 精神错乱。

Posttraumatic stress disorder (PTSD) is a highly prevalent and debilitating disorder. Despite efforts to characterize the pathophysiology of PTSD, no measurable indicators have been established to aid in diagnosis, treatment development, and prediction of treatment response. This K01 presents a program for research and training that will support the applicant on a path towards becoming an independent investigator, focused on the underlying neural mechanisms of learning valence discrimination within an environment using location-specific information through an interdisciplinary approach. The training plan builds on the candidate’s prior training and experience and capitalizes on a mentorship team and a research environment to foster development of the candidate’s expertise in 1) the understanding of neural and psychophysiological profiles related to PTSD, 2) gaining deeper proficiency in multimodal magnetic resonance imaging (MRI) data acquisition and analysis, 3) the understanding of mental disorder symptomatology and diagnosis & expertise in patient-related research, and 4) responsible conduct in scientific research. This research project will use a novel virtual reality task, created by the applicant and validated in healthy humans, to assess brain activity differences between patients with PTSD (n=30), trauma-exposed healthy controls (TEHC, n=30), and no trauma-exposed health controls (HC, n=30). A multimodal MRI approach (functional, resting-state, and structural MRI), will be used aiming to clarify the neural mechanisms underlying contextual threat discrimination in PTSD. Also, the fMRI will be coupled with peripheral measures of anxiety (e.g., skin conductance response, heart rate, breathing, pupillometry), subjective ratings of anxiety, and symptom clusters of PTSD. This research will be conducted at Columbia Medical Center, an optimal location due to the Anxiety Disorders Clinic, access to patients with PTSD within the PTSD research program, and imaging facilities. The results of the proposed research will be vital to clarify the process of discrimination of contextual threat in patients afflicted by anxiety disorders and PTSD and will lead to future R01 grants examining other threat-related learning processes across anxiety and trauma-related disorders. Together, the research and training experiences and expertise developed through this K01 award will support the applicant’s transition to research independence and ensure the applicant becomes a leading authority in the specific role of brain areas needed for threat learning and discrimination within an environment and how they break down in mental disorders.