Posttraumatic stress disorder (PTSD) is a chronic, disabling condition that occurs in a subgroup of individuals after experiencing traumatic stress, and is common in Veterans seeking mental health treatment at the VA. Although evidence-based psychosocial treatments exist for PTSD, a substantial portion of individuals do not fully respond to treatment. Thus, there is a clear need to continue researching novel interventions for PTSD in Veterans. Recently, new interventions for mental health disorders have utilized computerized cognitive training techniques in order to improve the functioning of cognitive systems and reduce symptoms. This type of intervention, often referred to as neurotherapeutics, may hold promise for PTSD as a method for ameliorating symptoms and improving cognition. Individuals with PTSD demonstrate difficulties with cognitive control functions, which appear to be causally implicated in symptoms of the disorder (e.g., intrusive trauma- related memories). To date the efficacy of neurotherapeutics for PTSD has been understudied in Veterans. The current proposal aims to bridge research on basic neurocognitive mechanisms of PTSD with intervention research by conducting a randomized controlled trial (RCT) of a cognitive control training program in 80 Veterans with PTSD. Veterans will complete computer-based training exercises designed to specifically target and improve aspects of cognitive control. Veterans will complete the program twice per week for eight weeks. Symptoms will be assessed before and after treatment, as well as at a two- month follow up time point. The primary goal of the study is to examine the effect of the intervention on PTSD symptoms and cognitive deficits. Evaluating symptom change as a result of the intervention will provide critical data regarding the utility of this program as a PTSD treatment. If effective, this training program could serve as alternative treatment option for Veterans with PTSD, and could be translated into an easily transportable intervention for dissemination (e.g., through web-based platforms). A secondary goal is to use functional magnetic resonance imaging (fMRI) to better understand the mechanisms by which cognitive training culminates in symptom reduction. If training cognitive control with neurotherapeutics directly enhances functioning of specific neural substrates as hypothesized, improvements in affective processes relying on shared neural regions would also be predicted. Modifying functioning in these substrates with training may thus reduce symptoms by improving neural functioning while processing and managing trauma-related affect and information. Neural systems used for cognitive control targeted in the training described (e.g., dorsolateral prefrontal cortex [dlPFC]) are also recruited when individuals mentally manipulate emotional information, such as when individuals use reappraisal to change the way that they think about negative emotional situations or content. In this study, Veterans will complete a neutral cognitive control task and a reappraisal task while undergoing fMRI before and after completing the training treatment. This will be the first study to evaluate neurobiological mechanisms of this type of training in PTSD, which is a fundamental next step for understanding how to improve the training program and who may be best served by completing it. Building upon the applicant's prior experience with clinical trials and cognitive training research, the proposed training plan provides an opportunity for new hands-on training in neuropsychology, cognitive rehabilitation, and functional neuroimaging techniques to meet the immediate goal of developing skills in these domains. Long term, the award will facilitate development of expertise with integration of neurobiological tools with intervention research, and provide critical pilot data for successful preparation of a VA Merit Award. Together, the research and training plan will make the applicant well-poised to transition to an independent clinical scientist role within the VA system.

Public Health Relevance

The proposal aims to evaluate the effect of a novel cognitive training intervention program on emotional and cognitive symptoms of posttraumatic stress disorder in Veterans using a randomized controlled trial design. The proposal also seeks to examine neurobiological mechanisms of generalization to symptom reduction. Using functional magnetic resonance imaging, the neural regions involved in neutral and affective cognitive control functioning will be examined before and after the intervention, and associations between neural regions and symptom reduction will be examined. The planned study will provide critical information about the efficacy of this type of program for Veterans with PTSD, while simultaneously informing neurobiological and cognitive models of the disorder that will allow for more precise treatment development and personalization.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Mental Health and Behavioral Science B (MHBB)
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VA San Diego Healthcare System
San Diego
United States
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