Project Summary PTSD is a highly debilitating and prevalent condition. Although a number of empirically supported interventions exist, response rates are suboptimal. One factor likely impeding treatment response is poor encoding, consolidation, and retrieval of the learning that occurs in therapy. Individuals with PTSD exhibit deficits in a number of cognitive domains related to learning and memory, particularly in the context of trauma-related stimuli, and pre-treatment memory capacity has consistently been shown to predict PTSD treatment response. Furthermore, poor memory of therapy content is common and is also associated with worse treatment outcome. Accordingly, the present study will examine the utility of integrating a Memory Support (MS) intervention into Cognitive Processing Therapy (CPT), an empirically supported and widely disseminated treatment for PTSD. MS was designed to integrate techniques aimed at facilitating encoding, consolidation, and retrieval of new learning into existing treatments, and has been shown to improve outcomes when integrated into cognitive therapy for depression. The proposed study will consist of an initial treatment adaption phase to optimize integration of MS into CPT, followed by a pilot randomized controlled trial comparing CPT with Memory Support (CPT+MS) to CPT-alone. The primary aim of the trial will be to determine if compared CPT+MS will lead to greater memory and learning of therapy content relative to CPT-alone (i.e. target engagement), and to establish the acceptability and feasibility of integration of MS into CPT. Secondary aims include a preliminary examination of treatment efficacy, as indicated by the magnitude of changes in PTSD symptoms between conditions, and target validation, as indicated by associations between memory and learning of therapy content and treatment response. Exploratory analyses will examine several indicators of baseline memory-related cognitive functioning as predictors of memory and learning of therapy content, providing preliminary data to inform future research on personalized application of MS. Results of the trial will advance scientific knowledge about methods for optimizing memory and learning as a mechanism for improving PTSD treatment outcomes. The proposed research and training plan will facilitate the applicant’s development into an independent investigator using an experimental therapeutics approach to enhance PTSD treatment outcomes. Mentorship and training will focus on: 1) mechanisms-focused clinical trial methodology; 2) application of basic learning and memory research to the assessment and improvement of memory during therapy; 3) treatment development and enhancement; 4) advanced longitudinal data analysis; and 5) grantsmanship and professional development. Research and training will take place at the National Center for PTSD at the VA Boston Healthcare System, and will be supported through mentorship from an accomplished team committed to the applicant...