Post-Concussion Brain Changes Relative to Pre-Injury White Matter and Cerebral Blood Flow

Medical clearance for return to play (RTP) after sports-related concussion is based on clinical assessment. It is unknown whether brain physiology has entirely returned to preinjury baseline at the time of clearance. In this longitudinal study, we assessed whether concussed individuals show functional and structural MRI brain changes relative to preinjury levels that persist beyond medical clearance. Secondary objectives were to test whether postconcussion changes exceed uninjured brain variability and to correlate MRI findings with clinical recovery time. For this prospective observational study, healthy athletes without a history of psychiatric, neurologic, or sensory-motor conditions were recruited from a single university sport medicine clinic. Clinical and MRI data were collected at preseason baseline, and those who were later concussed were reassessed at 1-7 days after injury, RTP, 1-3 months after RTP, and 1 year after RTP. A demographically matched control cohort of uninjured athletes was also reassessed at their subsequent preseason baseline. Primary outcomes were postconcussion changes in MRI measures of cerebral blood flow (CBF), white matter mean diffusivity (MD), and fractional anisotropy (FA), evaluated using mixed models. Secondary outcomes were group differences in MRI change scores and correlations of change scores with days to RTP. Of the 187 athletes enrolled in the study, 25 had concussion with follow-up imaging (20.3 ± 1.5 years, 56% male, 44% female) and were compared with 27 controls (19.7 ± 1.8 years, 44% male, 56% female). Concussed athletes showed statistically significant changes from baseline, including decreased frontoinsular CBF (mean and 95% CI -8.97 [-12.80, -5.01] mL/100 g/minute, z = -4.53), along with increased MD (1.94 × 10-5 [1.26, 2.69] × 10-5, z = 5.48) and reduced FA (-7.30 × 10-3 [-9.80, -5.05] × 10-3, z = -6.07) in the corona radiata and internal capsule. Effects persisted beyond RTP, although only CBF changes exceeded longitudinal variability in controls. For participants with longer recovery periods, significantly greater changes in medial temporal CBF were also seen (ρ = 0.64 [0.44, 0.81], z = 6.80). This study provides direct evidence of persistent postconcussion changes in CBF and white matter at RTP and up to 1 year later. These results support incomplete recovery of brain physiology at medical clearance, with secondary analyses emphasizing the sensitivity of CBF to clinical recovery.