MRI-based measures of intracortical myelin are sensitive to a history of TBI and are associated with functional connectivity.

Traumatic brain injuries (TBIs) induce persistent behavioral and cognitive deficits via diffuse axonal injury. Axonal injuries are often examined in vivo using diffusion MRI, which identifies damaged and demyelinated regions in deep white matter. However, TBI patients can exhibit impairment in the absence of diffusion-measured abnormalities, suggesting that axonal injury and demyelination may occur outside the deep white matter. Importantly, myelinated axons are also present within the cortex. Cortical myelination cannot be measured using diffusion imaging, but can be mapped in-vivo using the T1-w/T2-w ratio method. Here, we conducted the first work examining effects of TBI on intracortical myelin in living humans by applying myelin mapping to 46 US Military Veterans with a history of TBI. We observed that myelin maps could be created in TBI patients that matched known distributions of cortical myelin. After controlling for age and presence of blast injury, the number of lifetime TBIs was associated with reductions in the T1-w/T2-w ratio across the cortex, most significantly in a highly-myelinated lateral occipital region corresponding with the human MT+ complex. Further, the T1-w/T2-w ratio in this MT+ region predicted resting-state functional connectivity of that region. By contrast, a history of blast TBI did not affect the T1-w/T2-w ratio in either a diffuse or focal pattern. These findings suggest that intracortical myelin, as measured using the T1-w/T2-w ratio, may be a TBI biomarker that is anatomically complementary to diffusion MRI. Thus, myelin mapping could potentially be combined with diffusion imaging to improve MRI-based diagnostic tools for TBI.

High-Fidelity Measures of Whole-Brain Functional Connectivity and White Matter Integrity Mediate Relationships between Traumatic Brain Injury and Post-Traumatic Stress Disorder Symptoms.

Traumatic brain injury (TBI) disrupts brain communication and increases risk for post-traumatic stress disorder (PTSD). However, mechanisms by which TBI-related disruption of brain communication confers PTSD risk have not been successfully elucidated in humans. This may be in part because functional MRI (fMRI), the most common technique for measuring functional brain communication, is unreliable for characterizing individual patients. However, this unreliability can be overcome with sufficient within-individual data. Here, we examined whether relationships could be observed among TBI, structural and functional brain connectivity, and PTSD severity by collecting ∼3.5 hours of resting-state fMRI and diffusion tensor imaging (DTI) data in each of 26 United States military veterans. We observed that a TBI history was associated with decreased whole-brain resting-state functional connectivity (RSFC), while the number of lifetime TBIs was associated with reduced whole-brain fractional anisotropy (FA). Both RSFC and FA explained independent variance in PTSD severity, with RSFC mediating the TBI-PTSD relationship. Finally, we showed that large amounts of per-individual data produced highly reliable RSFC measures, and that relationships among TBI, RSFC/FA, and PTSD could not be observed with typical data quantities. These results demonstrate links among TBI, brain connectivity, and PTSD severity, and illustrate the need for precise characterization of individual patients using high-data fMRI scanning.