Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common co- occurring and debilitating conditions that affect many veterans of the post 9/11 conflicts. Recent studies suggest that mTBI and PTSD are associated with disruptions in brain structure and function. However, the mechanism linking mTBI and PTSD to these neural consequences are unclear. One possibility is that these conditions influence neural integrity through cerebrovascular dysfunction. This is consistent with recent research showing an association between mTBI and cerebrovascular dysfunction, but more work is needed to determine whether this association impacts neural integrity over time. Similarly, PTSD has been linked to disruptions in vascular health, with evidence suggesting an increased prevalence of peripheral metabolic conditions. However, it is unclear to what extent the peripheral vascular dysfunction reported in PTSD studies is also manifested in cerebrovascular dysfunction or to what extent the presence of PTSD might moderate the relationship between mTBI and poor cerebrovascular health. Complicating the picture even further, recent work suggests that individual differences in genetic factors may play a role in the relationship between mTBI and neural health, but it is unknown how or to what extent these genetic factors might influence the associations between mTBI and cerebrovascular dysfunction. The overarching goal of this proposal is to use a large, unique and rich longitudinal dataset of Operations Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) veterans to understand neural metabolic health in mTBI and how it relates to individual differences in genetics, PTSD, and neural integrity. The long-term goal is to discover treatment targets (pathways) that can lead to effective interventions and therapies for mTBI and PTSD. This proposal will support Dr. Sullivan?s training and research in cutting-edge and integrative techniques to study the neurobiology of mTBI and PTSD. Towards this goal, this application will provide the necessary training to lead a successful, independent program of research centered on veterans? health. Training goals of this application are: (1) learn cerebrovascular imaging techniques; (2) learn principles, methodology, and applications of human molecular genetics; and (3) learn advanced multivariate statistics and methods suitable for multi-modal and high-dimensional datasets. These training goals will be augmented by experimental training in four research aims: (1) examine associations between mTBI and cerebrovascular dysfunction; (2) examine the influence of genetic factors on neural metabolic stress and mTBI; (3) examine the influence of PTSD on the association between mTBI and cerebrovascular health; and (4) examine whether deficits in cerebrovascular function predict changes in neural integrity over time in mTBI. The primary hypotheses of this study are that mTBI is associated with disruptions in neural metabolic health; that genetic factors and PTSD will impact this association; and that mTBI influences overall brain integrity through its effect on neural metabolic health. Completion of these training and research goals will provide Dr. Sullivan the necessary tools to launch an independent VA career and provide important contributions to advance our understanding of the neurobiology of mTBI and PTSD.
Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common and debilitating conditions that affect many veterans. Both conditions have been associated with cerebrovascular and metabolic dysfunction, which may be linked to neurodegeneration and neural integrity loss. This study will use arterial spin labeling (ASL) in a large, well-characterized existing longitudinal dataset of Operation Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) veterans to examine the association between mTBI, PTSD, and cerebrovascular dysfunction. Further, this study aims to explore whether cerebrovascular dysfunction has any bearing on neurodegeneration longitudinally. The goal of this research is to use a multi-modal approach that combines neuroimaging, clinical neuroscience, and molecular genetics to address a critical gap in the understanding of the neurobiology of mTBI and PTSD.