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

Sustaining a traumatic brain injury (FBI) 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

Network diffusion modeling predicts neurodegeneration in traumatic brain injury

Objective Traumatic brain injury (TBI) is a heterogeneous disease with multiple neurological deficits that evolve over time. It is also associated with an increased incidence of neurodegenerative diseases. Accordingly, clinicians need better tools to predict a patient’s long‐term prognosis. Methods Diffusion‐weighted and anatomical MRI data were collected from 17 adolescents (mean age = 15y8mo) with moderate‐to‐severe TBI and 19 healthy controls. Using a network diffusion model (NDM), we examined the effect of progressive deafferentation and gray matter thinning in young TBI patients. Moreover, using a novel automated inference method, we identified several injury epicenters in order to determine the neural degenerative patterns in each TBI patient. Results We were able to identify the subject‐specific patterns of degeneration in each patient. In particular, the hippocampus, temporal cortices, and striatum were frequently found to be the epicenters of degeneration across the TBI patients. Orthogonal transformation of the predicted degeneration, using principal component analysis, identified distinct spatial components in the temporal–hippocampal network and the cortico‐striatal network, confirming the vulnerability of these networks to injury. The NDM model, best predictive of the degeneration, was significantly correlated with time since injury, indicating that NDM can potentially capture the pathological progression in the chronic phase of TBI. Interpretation These findings suggest that network spread may help explain patterns of distant gray matter thinning, which would be consistent with Wallerian degeneration of the white matter connections (i.e., “diaschisis”) from diffuse axonal injuries and multifocal contusive injuries, and the neurodegenerative patterns of abnormal protein aggregation and transmission, which are hallmarks of brain changes in TBI. NDM approaches could provide highly subject‐specific biomarkers relevant for disease monitoring and personalized therapies in TBI

Plasticity of executive functions after traumatic brain injury in adolescents

From daily clinical practice in the Child Rehabilitation Centre Ghent University Hospital, we experience that adolescents with a moderate to severe traumatic brain injury (TBI) do recover quite well when it comes to talking and walking. Adolescents frequently may appear to make a full physical recovery and at the end of the rehabilitation period do often perform within the average range in various physical and standardized neuropsychological assessments. However, regardless of their performance on standardized tests, everyday functioning at home or in school remains generally poor. ‘The hidden disability’ such as difficulties in executive function and sometimes an ‘unusual’ behaviour jeopardizes future socio-economic integration and can be deeply distressing for parents and siblings. More research is needed for a better comprehension of how a developing brain reacts on a traumatic insult and how we can foster reorganization and further maturation of the adolescent’s brain. Ultimately, answers to these questions will provide a foundation for more individualized therapeutic manipulation of neuroplasticity to enhance functional recovery in the traumatized developing brain

How to Train an Injured Brain? A Pilot Feasibility Study of Home-Based Computerized Cognitive Training

Objective: Computerized cognitive training programs have previously shown to be effective in improving cognitive abilities in patients suffering from traumatic brain injury ( TBI ). These studies often focused on a single cognitive function or required expensive hardware, making it difficult to be used in a home-based environment. This pilot feasibility study aimed to evaluate the feasibility of a newly developed, home-based, computerized cognitive training program for adolescents who suffered from TBI. Additionally, feasibility of study design, procedures, and measurements were examined. Design: Case series, longitudinal, pilot, feasibility intervention study with one baseline and two follow-up assessments. Materials and Methods: Nine feasibility outcome measures and criteria for success were defined, including accessibility, training motivation/user experience, technical smoothness, training compliance, participation willingness, participation rates, loss to follow-up, assessment timescale, and assessment procedures. Five adolescent patients ( four boys, mean age = 16 years 7 months, standard deviation = 9 months ) with moderate to severe TBI in the chronic stage were recruited and received 8 weeks of cognitive training with BrainGames. Effect sizes ( Cohen's d ) were calculated to determine possible training-related effects. Results: The new cognitive training intervention, BrainGames, and study design and procedures proved to be feasible; all nine feasibility outcome criteria were met during this pilot feasibility study. Estimates of effect sizes showed small to very large effects on cognitive measures and questionnaires, which were retained after 6 months. Conclusion: Our pilot study shows that a longitudinal intervention study comprising our novel, computerized cognitive training program and two follow-up assessments is feasible in adolescents suffering from TBI in the chronic stage. Future studies with larger sample sizes will evaluate training-related effects on cognitive functions and underlying brain structures