Exploration of gray matter correlates of cognitive training benefit in adolescents with chronic traumatic brain injury

Abstract

Sustaining a traumatic brain injury (TBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood. This study investigated gray matter plasticity following 2 months of cognitive training in young patients with TBI. Sixteen adolescents in the chronic stage of moderate-severe-TBI (9 male, mean age = 15y8m ± 1y7m) were enrolled in a cognitive computerized training program for 8 weeks (5 times/week, 40 min/session). Pre-and post-intervention, and 6 months after completion of the training, participants underwent a comprehensive neurocognitive test-battery and anatomical Magnetic Resonance Imaging scans. We selected 9 cortical-subcortical Regions-Of-Interest associated with Executive Functioning (EF-ROIs) and 3 control regions from the Desikan-Killiany atlas. Baseline analyses showed significant decreased gray matter density in the superior frontal gyri p = 0.033, superior parietal gyri p = 0.015 and thalamus p = 0.006 in adolescents with TBI compared to age and gender matched controls. Linear mixed model analyses of longitudinal volumetric data of the EF-ROI revealed no strong evidence of training-related changes in the group with TBI. However, compared to the change over time in the control regions between post-intervention and 6 months follow-up, the change in the EF-ROIs showed a significant difference. Exploratory analyses revealed a negative correlation between the change on the Digit Symbol Substitution test and the change in volume of the putamen (r = -0.596, p = 0.015). This preliminary study contributes to the insights of training-related plasticity mechanisms after pediatric-TBI.

Keywords: Cognitive rehabilitation; Executive function; Gray matter; Linear mixed model analyses; Neural plasticity; Pediatric traumatic brain injury.

Fig. 1

The estimated mean gray matter volume per region per group (TBI and control), adjusted for age, gender and total intracranial volume, parental education. The error bars represent FDR adjusted confidence intervals.

Fig. 2

Longitudinal change in cortical volume of the 9 EF-ROIs (blue) and 3 control regions (brown) in the group with TBI on the 3 time-points. The error bars represent FDR adjusted confidence intervals.

Fig. 3

Significant difference in change over time between the 3 control regions and the 9 EF-ROIs.