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

创伤后应激障碍（PTSD）是一种高度流行且使人衰弱的疾病。尽管努力 描述创伤后应激障碍的病理生理学，没有建立可测量的指标来帮助诊断， 治疗开发和治疗反应的预测。本K01提出了一个研究计划， 培训将支持申请人成为独立调查员，重点是 使用特定位置的环境中学习价歧视的潜在神经机制 通过跨学科的方法。培训计划建立在候选人之前的培训基础上， 经验，并利用导师团队和研究环境，以促进 候选人在1）与PTSD相关的神经和心理生理学特征的理解，2） 在多模态磁共振成像（MRI）数据采集和分析方面获得更深的熟练程度，3） 对精神障碍诊断学和诊断的理解以及患者相关研究的专业知识，以及 4)在科学研究中负责任的行为。该研究项目将使用一种新颖的虚拟现实任务， 由申请人在健康人中验证，以评估患有 创伤后应激障碍（n=30），创伤暴露的健康对照（TEHC，n=30），和没有创伤暴露的健康对照（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 PTSD中情境威胁辨别的神经机制。此外，功能磁共振成像将结合 焦虑的外围测量（例如，皮肤电导反应、心率、呼吸、瞳孔测量），主观 焦虑等级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， 由于焦虑症诊所的最佳位置，在PTSD研究中接触PTSD患者 程序和成像设备。拟议研究的结果将对澄清 在焦虑症和PTSD患者中区分情境威胁，并将导致未来的R01 研究焦虑和创伤相关障碍的其他与威胁相关的学习过程。在一起， 通过K01奖开发的研究和培训经验和专业知识将支持 申请人的过渡到研究的独立性，并确保申请人成为一个领先的权威， 在环境中进行威胁学习和辨别所需的大脑区域的具体作用，以及它们如何 精神失常

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.