Sport-Related Concussion in Adolescent Athletes is Associated with Acute White Matter Alterations, Delayed Network Changes, and Individual-Level Injury Patterns

<jats:title>ABSTRACT</jats:title> <jats:p>Sport-related concussions (SRC) are heterogenous injuries that produce a variety of symptoms and recovery trajectories. This heterogenous nature and focus on group-level analyses in current literature may obscure individual level results that could better inform clinical SRC management. In a prospective case-control study, we used diffusion magnetic resonance imaging (dMRI) to quantify longitudinal, whole-brain microstructural white matter changes reflecting axonal injury and inflammation and structural network-level alterations following SRC in adolescent athletes. Differential tractography assessed individual white matter track changes from acute injury to clinical recovery on an individual level. Acutely after SRC, but not after recovery, concussed adolescents demonstrated increased (i) quantitative anisotropy, (ii) restricted diffusion imaging, and (iii) isotropy, indicating increased microstructural disruptions early after injury. At the network level, differences were seen not acutely but after clinical recovery: whole brain network structure was more similar with reduced capacity for information spread among the concussed adolescents compared with controls. At the individual level, consistent patterns of damaged white matter tracks persisted in the concussed males but not in the concussed females. These results indicate that adolescent athlete brains are impacted acutely at the microstructural level following SRC, but that macroscale network disruptions appear after microstructure damage resolution, and they can persist beyond clinical recovery. Sex differences in the brain’s microstructural response to SRC, highlight the need for future research to include individualized and sex-stratified analyses to guide targeted SRC management.</jats:p>