Premature white matter microstructure in female children with a history of concussion

Abstract

Childhood concussion may interfere with neurodevelopment and influence cognition. Females are more likely to experience persistent symptoms after concussion, yet the sex-specific impact of concussion on brain microstructure in children is understudied. This study examined white matter and cortical microstructure, based on neurite density (ND) from diffusion-weighted MRI, in 9-to-10-year-old children in the Adolescent Brain Cognitive Development Study with (n = 336) and without (n = 7368) a history of concussion, and its relationship with cognitive performance. Multivariate regression was used to investigate relationships between ND and group, sex, and age in deep and superficial white matter, subcortical structures, and cortex. Partial least square correlation was performed to identify associations between ND and performance on NIH Toolbox tasks in children with concussion. All tissue types demonstrated higher ND with age, reflecting brain maturation. Group comparisons revealed higher ND in deep and superficial white matter in females with concussion. In female but not male children with concussion, there were significant associations between ND and performance on cognitive tests. These results demonstrate a greater long-term impact of childhood concussion on white matter microstructure in females compared to males that is associated with cognitive function. The increase in ND in females may reflect premature white matter maturation.

Keywords: Cognition; Concussion; Females; Pediatric; Restriction spectrum imaging.

Fig. 1

Group differences in mean neurite density (ND) between concussion and comparison groups stratified by sex. (A & C) Mean ND in children with concussion and comparison group. Females with concussion had higher mean ND in (A) deep white matter and (C) superficial white matter. There were no group differences in males. (B & D) Regression lines showing relationships between age and mean white matter ND in children with concussion and the comparison group. (B) In the deep white matter and (D) superficial white matter, females with concussion had higher mean ND than the comparison group, and females and males in the concussion and comparison groups had similar trajectories of increasing ND with age. Asterisks indicate significant group differences (P < .05).

Fig. 2

Correlation between deep white matter neurite density and scores on cognitive measures of the NIH Toolbox. (A) Deep white matter loadings that contribute to LV1. Dotted red line indicates loadings with bootstrap ratios greater than |1.96| (equivalent to a p value of .05). Deep white matter tracts with the highest loadings include the corpus collosum, forceps major, and forceps minor. (B) Loadings of cognitive measures that contribute to LV1. Error bars represent 95% confidence intervals and significant loadings have error bars that do not cross 0. Significant cognitive measures include the Picture Sequence Memory (positive association with ND) Test and Picture Vocabulary Test (negative association with ND). LH: Left hemisphere; RH: Right hemisphere.

Fig. 3

Correlation between superficial white matter neurite density and scores on cognitive measures of the NIH Toolbox. (A) Superficial white matter loadings that contribute to LV1. Dotted red line indicates loadings with bootstrap ratios greater than |1.96| (equivalent to a p value of.05). Superficial white matter tracts with the highest loadings include the right supramarginal, left lateral orbitofrontal, and left precentral gyri. (B) Loadings of cognitive measures that contribute to LV1. Error bars represent 95% confidence intervals and significant loadings have error bars that do not cross 0. Significant cognitive measures include the Pattern Comparison Processing Speed Test (negative association with ND) and Picture Vocabulary Test (negative association with ND). LH: Left hemisphere; RH: Right hemisphere.