The Functional Connectome and Long-Term Symptom Presentation Associated With Mild Traumatic Brain Injury and Blast Exposure in Combat Veterans

Mild traumatic brain injury (TBI) sustained in a deployment environment (deployment TBI) can be associated with increased severity of long-term symptom presentation, despite the general expectation of full recovery from a single mild TBI. The heterogeneity in the effects of deployment TBI on the brain can be difficult for a case-control design to capture. The functional connectome of the brain is an approach robust to heterogeneity that allows global measurement of effects using a common set of outcomes. The present study evaluates how differences in the functional connectome relate to remote symptom presentation following combat deployment and determines if deployment TBI, blast exposure, or post-traumatic stress disorder (PTSD) are associated with these neurological differences. Participants included 181 Iraq and Afghanistan combat-exposed Veterans, approximately 9.4 years since deployment. Structured clinical interviews provided diagnoses and characterizations of TBI, blast exposure, and PTSD. Self-report measures provided characterization of long-term symptoms (psychiatric, behavioral health, and quality of life). Resting-state magnetoencephalography was used to characterize the functional connectome of the brain individually for each participant. Linear regression identified factors contributing to symptom presentation including relevant covariates, connectome metrics, deployment TBI, blast exposure PTSD, and conditional relationships. Results identified unique contributions of aspects of the connectome to symptom presentation. Furthermore, several conditional relationships were identified, demonstrating that the connectome was related to outcomes in the presence of only deployment-related TBI (including blast-related TBI, primary blast TBI, and blast exposure). No conditional relationships were identified for PTSD; however, the main effect of PTSD on symptom presentation was significant for all models. These results demonstrate that the connectome captures aspects of brain function relevant to long-term symptom presentation, highlighting that deployment-related TBI influences symptom outcomes through a neurological pathway. These findings demonstrate that changes in the functional connectome associated with deployment-related TBI are relevant to symptom presentation over a decade past the injury event, providing a clear demonstration of a brain-based mechanism of influence.