Posttraumatic Stress Disorder (PTSD) is a highly prevalent, chronic psychiatric disorder that imposes a major health burden on our returning Veterans. Moreover, PTSD is associated with marked occupational and social dysfunction, and high degrees of psychiatric and medical comorbidity. Despite its prevalence and devastating impact, available treatments, including evidence-based psychotherapy, are not sufficiently efficacious. Therefore, innovative interventions for the treatment of PTSD are sorely needed for Veterans suffering from PTSD. The application of non-invasive neuromodulation technologies is developing rapidly across neuro- psychiatry. The availability of new devices, coupled with increased knowledge of underlying neurocircuitry relevant to psychiatric illness, sets the stage for economically advantageous and innovative clinical applications of technologies for PTSD rehabilitation. Furthermore, rodent models and our previous pilot research indicate the therapeutic potential for combining non-invasive brain stimulation with exposure for PTSD. However to determine the real-world utility of combining brain stimulation with exposure, it is essential to examine how this combination reduces PTSD symptoms and improves quality of life or social and occupational function (QOL/SOF). The aim of the proposed research is to examine whether non-invasive brain stimulation can be combined with standardized, virtual-reality (VR) based exposure as an intervention for PTSD in Veterans. This study will use transcranial direct current stimulation (tDCS) targeting brain regions involved in PTSD, with stimulation delivered during VR. tDCS+VR holds particular promise for PTSD as this combination leverages the potential efficacy of both interventions, and provides a standardized exposure regimen that can be systemically evaluated. This application builds on our pilot work, demonstrating the technical feasibility of tDCS+VR, by proposing an adequately powered, randomized controlled trial of tDCS+VR in which 90 Veterans with PTSD will be randomized to receive either active tDCS or sham during VR. Three Specific Aims will be evaluated: 1) Prospectively examine the efficacy of tDCS+VR in Veterans with chronic PTSD, 2) Examine the relationship between PTSD-related psychophysiology, PTSD symptoms and QOL/SOF, and 3) Explore the relationship between changes in neural circuitry, PTSD and QOL/SOF. Addressing these Aims will provide the necessary data and experience to guide implementation research of tDCS+VR to reduce PTSD symptoms and improve QOL/SOF. Ultimately, this line of research can be expected to have an important positive impact toward achieving our long-term goal of integrating neuromodulation into PTSD treatment as a valuable, practical, and accessible option to improve the lives of our Veterans. ! !