Disrupted maturation of white matter microstructure after concussion is associated with internalizing behavior scores in female children.

BACKGROUND: Some children, particularly females, who experience concussions develop long-lasting emotional and behavioral problems. Establishing the potential contribution of pre-existing behavioral problems and disrupted white matter maturation has been challenging due to a lack of pre-injury data.

METHODS: From the Adolescent Brain Cognitive Development cohort, 239(90F) children aged 12.1±0.6 years who experienced a concussion after study entry at 10.0±0.6 years, were compared to 6,438(3,245F) children without head injuries aged 9.9±0.6 years at baseline and 12.0±0.6 years at follow-up. Child Behavior Checklist assessed internalizing and externalizing behavior at study entry and follow-up. In the children with MRI data available (concussion n=134; comparison n=3,520), deep and superficial white matter was characterized by neurite density from restriction spectrum image modeling of diffusion MRI. Longitudinal ComBat harmonization removed scanner effects. Linear regressions modeled 1) behavior problems at follow-up controlling for baseline behavior, 2) impact of concussion on white matter maturation, and 3) contribution of deviations in white matter maturation to post-concussion behavior problems.

RESULTS: Only female children with concussion had higher internalizing behavior problem scores. The youngest children with concussion showed less change in superficial white matter neurite density over two years compared to children with no concussion. In females with concussion, less change in superficial white matter neurite density correlated with increased internalizing behavior problem scores.

CONCLUSIONS: Concussions in female children are associated with emotional problems beyond pre-injury levels. Injury to superficial white matter may contribute to persistent internalizing behavior problems in females.