The VA RR&D TBI National Network Research Center based at VA Boston Healthcare System, with a network site at the Michael E. DeBakey VA Medical Center, called the Translational Research Center for TBI and Stress Disorders (TRACTS) (funded initially in 2009) proposes to continue its mission of conducting multidisciplinary, clinical research aimed at providing a psychological, biological and neurobiological characterization of the effects of traumatic brain injury (TBI) and related stress disorders, and to use this understanding to create effective treatment opportunities for Veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND). Over the last funding period, TRACTS has made remarkable progress in understanding the synergistic effect of mild traumatic brain injury (mTBI) and exposure to blast munitions on the mental and physical health of Veterans. This foundational work, which holistically has integrated psychological, biological, and epidemiological approaches to the study of the long- term effects of brain injury incurred during war, has led to the emerging concept of “Deployment Trauma” (DT) and helped create a roadmap toward the treatment and rehabilitation of the complex and interacting issues that define the civilian experience of Veterans in the post 9/11 era. It is our overarching goal and unifying mission to identify, understand, and treat the long-term effects of deployment trauma in our post 9/11 Veterans. Over the next funding period, the TRACTS infrastructure will be used to continue to grow and maintain the TRACTS cohort and the TRACTS prospective longitudinal cohort study, as well as the resultant TRACTS Data Repository. In the current application, we propose to investigate three interlocking Focus Areas (FA) that speak to critical gaps in our knowledge that must be addressed if we are to be successful in reaching our goals. These focus areas build upon our foundational observations over the last 8+ years and use this evolving wealth of information regarding the clinical presentation and endophenotypes of deployment trauma in OEF/OIF/OND Veterans to develop rehabilitative treatments that will foster civilian reintegration and reduce psychological and medical symptom severity. The three focus areas are: FA1: Deep phenotyping of DT and its functional consequences; FA 2: Understanding the dynamic interplay between biology and behavior that determines the biological and functional consequences of DT; FA 3: Rehabilitation and treatment of the functional and neurobiological consequences of DT. TRACTS will continue in its mission to provide the next generation of VA researchers with an innovative and outstanding mentoring environment at both the VA Boston and Houston Medical Centers through training in assessment, and rehabilitation and clinical neuroscience research. Our affiliations with other programs within VA, such as the National Centers for PTSD, MAVERIC, PTSD/TBI Brain Bank, as well as our affiliated universities, ensure that we have rich resources for excellence in training opportunities for undergraduates, graduate students, neuropsychology interns and post docs, and geriatric, neuropsychiatry and polytrauma fellows. Finally, TRACTS has initiated a wide-ranging education, outreach and dissemination effort intended to reach a broad audience of researchers, clinicians, Veterans and their families. This effort has included the provision of clinical training/education on the clinical complexities and idiosyncrasies of the OEF/OIF/OND population to researchers and clinicians, development of collaborative relationships within the greater Boston and Houston communities, and provide psychoeducation and resources to returning Veterans and their loved ones. In sum, TRACTS is well poised to continue its cutting-edge work over the next five years. The knowledge gleaned from the neuroscience and rehabilitation research conducted at TRACTS will continue to fill current gaps in diagnostics and therapeutics for Veterans with mTBI, blast, and stress-related disorders.

A significant minority of Veterans who have served in OEF/OIF/OND have returned home with debilitating co- occurring psychological and physical conditions that include, most notably, mild Traumatic Brain Injury (mTBI) and exposure to blast munitions, Posttraumatic Stress Disorder (PTSD), Mood and Anxiety Disorders, Substance Use Disorders, as well as chronic pain and sleep syndromes. It is the work of the TRACTS NNRC to foster clinical neuroscience and rehabilitation research that will help us to define the underlying biological, neurobiological and psychological nature of the injuries that these individuals have experienced and to identify who is most at risk for long-term functional decline resulting from these injuries. Armed with that knowledge, TRACTS seeks to adapt or define new rehabilitation strategies to help suffering Veterans transition back into family life and society. In this way, our goal is to not only assist the VA in providing state-of-the-art research into Veteran health, but we hope to make a positive impact on the lives of Veterans, their families, and society.