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

创伤后应激障碍中特定地点情境威胁歧视的神经相关性

• 批准号: 9789975
• 负责人: Benjamin Suarez-Jimenez
• 金额: $ 18.33万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789975
• 关键词: Advanced Development; Anterior; Anxiety; Anxiety Disorders; Area; Biological Markers; Brain; Breathing; Characteristics; Clinic; Communication; Coupled; Cues; Dangerousness; Data; Data Analyses; Detection; Development; Diagnosis; Diagnostic; Discrimination; Discrimination Learning; Disease; Distal; Emotional; Ensure; Environment; Feeling; Flowers; Fostering; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Galvanic Skin Response; Goals; Grant; Health; Heart Rate; Hippocampus (Brain); Human; Impairment; Intervention; Knowledge; Learning; Light; Location; Magnetic Resonance Imaging; Measurable; Measures; Medical center; Mental disorders; Mentored Research Scientist Development Award; Mentorship; National Institute of Mental Health; Neurobiology; Outcome; Outcome Study; Participant; Pathway Analysis; Patients; Peripheral; Post-Traumatic Stress Disorders; Prediction of Response to Therapy; Prefrontal Cortex; Process; Psychological reinforcement; Psychopathology; Psychophysiology; Research; Research Personnel; Research Project Grants; Research Training; Rest; Risk; Role; Safety; Severities; Shock; Specificity; Stimulus Generalization; Structure; Symptoms; Time; Training; Trauma; anxiety symptoms; anxiety-related disorders; authority; brain behavior; clinical phenotype; clinically relevant; conditioning; data acquisition; design; experience; imaging approach; imaging facilities; interdisciplinary approach; learned behavior; multimodality; neural circuit; neural correlate; neuroimaging; neuromechanism; novel; programs; recruit; relating to nervous system; response; skills; stem; symptom cluster; symptomatology; therapy development; trauma exposure; virtual reality

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.

创伤后应激障碍（PTSD）是一种非常普遍且令人衰弱的疾病。尽管努力 描述 PTSD 的病理生理学特征，尚未建立可测量的指标来帮助诊断， 治疗开发和治疗反应预测。 K01 提出了一个研究和计划 培训将支持申请人成为一名独立调查员，重点关注 使用特定位置在环境中学习价辨别的潜在神经机制 通过跨学科方法获取信息。培训计划建立在候选人之前的培训和 经验并利用导师团队和研究环境来促进发展 候选人在 1) 与 PTSD 相关的神经和心理生理学特征的理解，2) 方面的专业知识 更深入地熟练掌握多模态磁共振成像 (MRI) 数据采集和分析，3) 对精神障碍症状学和诊断的理解以及患者相关研究的专业知识，以及 4）负责任的科学研究行为。该研究项目将使用一种新颖的虚拟现实任务，创建 由申请人提出并在健康人类中得到验证，以评估患有以下疾病的患者之间的大脑活动差异 PTSD（n = 30），遭受过创伤的健康对照（TEHC，n = 30），以及没有遭受过创伤的健康对照（HC， n=30）。将使用多模式 MRI 方法（功能性、静息态和结构性 MRI），旨在阐明 PTSD 情境威胁歧视背后的神经机制。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、瞳孔测量）、主观 焦虑评级和 PTSD 症状群。这项研究将在哥伦比亚医学中心进行， 焦虑症诊所的最佳位置，可在 PTSD 研究中接触 PTSD 患者 程序和成像设施。拟议研究的结果对于阐明这一过程至关重要 患有焦虑症和创伤后应激障碍 (PTSD) 的患者对情境威胁的歧视，并将导致未来的 R01 拨款检查焦虑和创伤相关疾病中其他与威胁相关的学习过程。一起， 通过该 K01 奖项开发的研究和培训经验以及专业知识将支持 申请人向研究独立性的过渡，并确保申请人成为该领域的领先权威 环境中威胁学习和歧视所需的大脑区域的具体作用以及它们如何 精神失常。