The neurocognitive correlates of DTI indicators of white matter disorganization in pediatric moderate-to-severe traumatic brain injury

Introduction: Neuroimaging has expanded our understanding of pediatric brain disorders in which white matter organization and connectivity are crucial to functioning. Paralleling the known pathobiology of many neurodevelopmental disorders, traumatic brain injury (TBI) in childhood can alter trajectories of brain development. Specifically, diffusion tensor imaging (DTI) studies in TBI have demonstrated white matter (WM) abnormalities that suggest microstructural disruptions that may underlie atypical neurodevelopment. The neurocognitive correlates of these previous findings will be explored in this study.

Methods: Indicators of WM organization were collected in 44 pediatric patients with moderate/severe TBI and 76 controls over two post-injury time points: T1 (8-20 weeks) and T2 (54-96 weeks). Our previous work identified two TBI subgroups based on information processing differences: one with slower interhemispheric transfer times (IHTT) of visual information than controls and another with comparable IHTT. We extend this prior work by evaluating neurocognitive trajectories associated with divergent WM structure post-injury in slow and normal IHTT TBI subgroups.

Results: At T1, both TBI subgroups performed significantly worse than controls on a norm-referenced working memory index (WMI), but only the Normal IHTT TBI subgroup significantly improved over the 12-month follow-up period (p = 0.014) to match controls (p = 0.119). In contrast, the Slow IHTT TBI subgroup did not show any recovery in working memory performance over time and performed more poorly than the control group (p < 0.001) at T2. Improvement in one of the two WMI subtests was associated with DTI indicators of WM disorganization in CC tracts to the precentral, postcentral, frontal, and parietal cortices. IHTT and WM mean diffusivity predicted 79% of the variance in cognitive recovery from T1 to T2 when also accounting for other known predictors of TBI recovery.

Discussion: In the year following TBI, some pediatric patients experienced persisting working memory disturbance while others exhibited recovery; stratification was based on an event-related potential marker. More or less improvement in neurocognition was also associated with the degree of WM disorganization. IHTT, measured post-acutely after TBI, and progression of WM disorganization over time predicted neurocognitive trajectories at the chronic timeframe - potentially representing a prognostic biomarker.