Cerebral Perfusion and Cognitive Outcomes in Mild Traumatic Brain Injury

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PROJECT SUMMARY/ABSTRACT It has been estimated that approximately 20% of U.S. service members returning from the recent wars in Iraq and Afghanistan have suffered at least one head injury during deployment. Nearly 83% of these injuries can be classified as mild and are the direct result of either blunt-force (i.e., direct blow to the head) or blast-related (i.e., high pressure from an improvised explosive device) trauma. Though the short and long-term consequences of neurotrauma are now only beginning to be appreciated, those with history of mild traumatic brain injury (mTBI) show increased rates of disability and psychiatric disorders, decreased quality of life, significant cognitive deficits, and troublesome experience of post-concussive symptoms (PCS), relative to those with no history of mTBI. Though vastly understudied, the role of the cerebrovascular dysfunction in outcomes after mTBI has recently begun to garner increasing attention. Importantly, the brain is reliant on steady cerebral blood flow (CBF) to carry out a host of functional processes and maintain neuronal integrity. Brief fluctuations and/or prolonged alterations in cerebral blood flow (CBF) have been linked to negative pathological consequences (e.g., neurodegeneration, ischemia) and cognitive dysfunction. Within the context of mTBI, biomechanical and animal models suggest that primary structural alterations to vasculature or brain parenchyma supplied by microvasculature coupled with secondary cellular and/or molecular initiated neuroinflammatory cascades could greatly alter CBF post-injury. Therefore, there is a critical need to understand and clarify the nature of CBF alterations and its potential contributions to negative health outcomes in mTBI, particularly in chronic stages. The current proposal therefore seeks to use state-of-the art, non-invasive, multi-phase pseudo-continuous arterial spin labeling (MPPCASL) neuroimaging methods to:  (1) evaluate whether CBF changes occur in those with history of mTBI; (2) investigate the relationship between resting CBF and neuropsychological function; and (3) in exploratory analyses, examine possible mediators and/or moderators of resting CBF and cognition in those with history of mTBI. Importantly, understanding the nature and underlying contribution of CBF to poor outcomes in those with mTBI will help inform prevention and interventional strategies that are currently being developed to mitigate negative health consequences for those who have sustained head trauma. Specifically, information gleaned from this proposal has the potential to improve diagnosis, aid in symptom management, and possibly provide a useful biomarker of both impairment and recovery in a vulnerable population where persistent neurological and behavioral dysfunction remains poorly understood.