Structural-covariance networks identify topology-based cortical-thickness changes in children with persistent executive function impairments after traumatic brain injury

Paediatric traumatic brain injury (pTBI) results in inconsistent changes to regional morphometry of the brain across studies. Structural-covariance networks represent the degree to which the morphology (typically cortical-thickness) of cortical-regions co-varies with other regions, driven by both biological and developmental factors. Understanding how heterogeneous regional changes may influence wider cortical network organization may more appropriately capture prognostic information in terms of long term outcome following a pTBI. The current study aimed to investigate the relationships between cortical organisation as measured by structural-covariance, and long-term cognitive impairment following pTBI. T1-weighted magnetic resonance imaging (MRI) from n = 83 pTBI patients and 33 typically developing controls underwent 3D-tissue segmentation using Freesurfer to estimate cortical-thickness across 68 cortical ROIs. Structural-covariance between regions was estimated using Pearson's correlations between cortical-thickness measures across 68 regions-of-interest (ROIs), generating a group-level 68 x 68 adjacency matrix for patients and controls. We grouped a subset of patients who underwent executive function testing at 2-years post-injury using a neuropsychological impairment (NPI) rule, defining impaired-and non-impaired subgroups. Despite finding no significant reductions in regional cortical-thickness between the control and pTBI groups, we found specific reductions in graph-level strength of the structural covariance graph only between controls and the pTBI group with executive function (EF) impairment. Node-level differences in strength for this group were primarily found in frontal regions. We also investigated whether the top n nodes in terms of effect-size of cortical-thickness reductions were nodes that had significantly greater strength in the typically developing brain than n randomly selected regions. We found that acute cortical-thickness reductions post-pTBI are loaded onto regions typically high in structural covariance. This association was found in those patients with persistent EF impairment at 2-years post-injury, but not in those for whom these abilities were spared. This study posits that the topography of post-injury cortical-thickness reductions in regions that are central to the typical structural-covariance topology of the brain, can explain which patients have poor EF at follow-up.

Automated summary

Pediatric traumatic brain injury can lead to inconsistent changes in brain morphology, with this study focusing on the relationship between cortical organization and long-term cognitive impairment post-pTBI. While specific reductions were found in structural covariance strength between controls and pTBI patients with executive function impairment, node-level differences were primarily in frontal regions. The study suggests that post-injury cortical thickness reductions in regions central to structural covariance topology may explain poor executive function outcomes in some patients.