Sex-specific hippocampal microstructural alterations in 11-12-year-old adolescents with a history of mild traumatic brain injury

Abstract

Mild traumatic brain injury (mTBI) is common in children and adolescents and frequently accompanied by transient cognitive and emotional disturbances. While pediatric mTBI can shape subsequent brain maturation, its impact on neurodevelopmental trajectories remains poorly understood, particularly regarding hippocampal microstructure, a region critical for memory and highly vulnerable to brain injury. Using restriction spectrum imaging (RSI) data from the Adolescent Brain Cognitive Development Study (ABCD Study ; n = 4,399), this study aimed to characterize hippocampal microstructural alterations in adolescents (aged 11-12 years) with a history of mTBI and to examine their associations with verbal learning and memory performance on the Rey Auditory Verbal Learning Test (RAVLT). Sex-stratified analyses were performed considering potential sex differences in vulnerability and responses to brain injury. History of mTBI was assessed using the modified Ohio State University TBI Screen-Short Version, a retrospective parent report. Male adolescents with a history of mTBI exhibited higher hippocampal restricted normalized diffusion (RND) than their peers without mTBI (Bonferroni-corrected p = 0.02), whereas no group differences were observed in females. Within the male mTBI group, higher hippocampal RND was positively associated with both immediate ( p = 0.01) and delayed ( p = 0.04) recall scores on the RAVLT, suggesting potential adaptive or reparative neuroplastic processes following injury. These findings demonstrate sex-specific hippocampal microstructural alterations in young adolescents with a history of mTBI, highlighting potential neuroplastic adaptations during development. Although causal inference is limited given the cross-sectional design of the analysis, and mTBI history was based on retrospective parent report, the results underscore the importance of considering sex differences in recovery mechanisms and may inform future efforts to identify neuroimaging biomarkers that predict recovery trajectories and guide targeted interventions.