Traumatic brain injury (TBI) is becoming an increasing concern for the Veterans Administration, as the number of returning soldiers who have acquired a TBI in combat continues to rise. Still, little is known about the relationship between brain injury severity, resultant neuropathology, and subsequent neurobehavioral disability. At present, we still lack a clear biomarker of TBI that is both sensitive to the history and/or presence of injury, and one that scales with severity of injury. Therefore, the overall objective of the proposed research is to fill this need by validating an in vivo, non-invasive biomarker for TBI diagnosis. Through the use of diffusion tensor imaging (DTI), we seek to investigate the integrity of specific white matter tracts in the thalamus and brainstem, in the hopes of identifying a potential consistent biomarker of TBI. To accomplish our objectives, we will recruit a total of 72 veterans with a history of mild TBI due to blast-related injury, 24 non-injured controls and 24 extra-cranial injured controls. Patients will be matched for post traumatic stress disorder symptom severity, time in theater and combat exposure. Patients will also complete a 3 Tesla MRI with high resolution DTI of the thalamus and brain stem, and structural imaging to quantify atrophy and lesions. In addition, in order to evaluate the functional integrity of the brain stem-thalamic-prefrontal circuit, tests of oculomotor function (fixation, visually guided saccades, anti-saccades) will be administered. Cognition, post-concussive symptoms, mood, anxiety and post traumatic stress disorder symptoms will be evaluated using a battery of neuropsychological tests sensitive to mild TBI. The data will be analyzed to determine whether (a) thalamus projection fibers and (b) brain stem fibers are affected by blast-related TBI and determine whether damage to these fibers results in neurophysiologic and neuropsychological impairment. The primary outcome will determine whether this measure is clinically relevant in returning OIF/OEF veterans, and whether or not these methods are valid in assessing and diagnosing mild TBI due to secondary blast injury.
The proposed research has the potential to impact veteran's health in numerous ways. First, basic characterization on the effects of blast on brain structure and function is not known and would be advanced by the proposed studies. In addition, the study would potentially validate a traumatic brain injury (TBI) biomarker that would allow diagnosis based upon quantitative and independent assessment of injury, allowing for accurate characterization, reduction of post-traumatic syndrome systems being misdiagnosed as PTSD, and/or reduction of PTSD patients being misdiagnosed with TBI. Also, this biomarker would potentially alter therapeutic targets and provide a strong foundation for evaluation of interventions and facilitate the development of novel treatment strategies. Finally, oculomotor testing has the promise of being an efficient clinical diagnostic assessment of neurophysiological function.
