Neural Correlates of Location-Specific Contextual Threat Discrimination in Post-Traumatic Stress Disorders REV1

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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 the University of Rochester, an optimal location due to the hospital and access to patients with PTSD, 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.