Prolonged White Matter Remodeling Trajectories Predict Cognitive and Emotional Recovery After Mild Traumatic Brain Injury

Traumatic brain injury (TBI) disrupts white matter tracts essential for cognition and emotion. Although diffusion tensor imaging (DTI) can noninvasively measure white matter structure, it has been inconsistent in predicting recovery from TBI, likely due to complex, individual-specific dynamics of post-TBI white matter remodeling. Here, we employed dense longitudinal neuroimaging to track white matter recovery weekly over six months after complicated mild TBI in a single 21 y.o. patient (motor vehicle collision; Glasgow Coma Score = 15; no loss of consciousness or post-traumatic amnesia; visible right temporal subdural hematoma) and a 24 y.o. control. Across both individuals, we collected 56 MRI sessions totaling over 2,500 minutes of high-quality scanning and matched behavioral assessments, offering an exceptionally dense view of within-participant white matter remodeling. In the patient, but not the control, fractional anisotropy (FA)—a widely used DTI metric—showed sustained decreases across many tracts before reversing course around 18 weeks post-injury, suggesting nonlinear and prolonged reorganization. These continuous changes in FA also mediated improvements in cognitive and emotional function, implying that FA reflects active recovery processes, not just damage. Diffusion basis spectrum imaging (DBSI) revealed an initial phase of cellular loss, followed by inflammatory remodeling, vascular adaptation, and persistent metabolic activity. These brain changes lasted over six months, far exceeding the few days of cognitive rest typically recommended in clinical care. These findings challenge current return-to-activity guidelines and suggest the possibility of tailoring rehabilitation timing to individual patterns of brain recovery, rather than relying on broad, standardized recovery windows.