Neural mechanisms involved in contextual processing in PTSD

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Summary/Abstract Posttraumatic stress disorder (PTSD) is a serious and debilitating condition, characterized by changes in fear expression and modulation. The fear modulation deficits in PTSD patients likely stem, at least in part, from difficulties using “safe” and “danger” contexts to disambiguate potentially threatening cues. A number of cognitive deficits may underlie impaired contextual processing in PTSD, including deficits in encoding and retrieval of contextual information. Pattern separation (ability to distinguish between similar but different stimuli) and pattern completion (ability to identify a previously encoded stimulus based on partial information) are believed to underlie memory encoding and retrieval, respectively. The goal of this project is to systematically probe memory function, like pattern separation and pattern completion in PTSD patients, trauma exposed controls (TC), and healthy controls (HC) using neurocognitive tasks and a fear learning task. We will investigate the roles of memory for context and pattern separation/completion in the modulation of fear expression. We aim to examine 1) Pattern Separation and Pattern Completion abilities in PTSD and the underlying neural circuits, and 2) Relationships between Pattern Separation and Pattern Completion abilities and context processing deficits during fear learning in PTSD. Participants will complete a fear learning task to assess contextual processing and fear modulation. Memory for contextual information, pattern separation, and pattern completion will be examined during MRI scanning to identify associated hippocampal and prefrontal cortex activation patterns. Brain activation and behavioral performance will be compared between PTSD, TC, and HC groups across all tasks to better understand contributions of these hippocampal deficits to altered fear learning and reactivity in PTSD. In order to successfully complete the proposed project, training objectives include 1) advanced MRI processing and analysis, 2) hippocampal mechanisms of learning and memory, 3) neurocognitive assessment of PTSD, and 4) clinical translational neuroscience. This proposed NIMH K23 award will provide rich pilot data for an R-level application and protected time for the candidate to obtain advanced training in neuroimaging methods, while broadening her expertise in neurocognitive mechanisms underlying anxiety disorder presentations. The outcome of this project has strong potential to enhance our understanding of mechanisms involved in PTSD development and maintenance, to eventually improve existing treatments.