A Preliminary DTI Tractography Study of Developmental Neuroplasticity 5-15 Years After Early Childhood Traumatic Brain Injury.

Elisabeth A Wilde,Harvey S Levin,Erin D Bigler,Marianne Macleod,Zili D Chu,Linda J Noble-Haeusslein,Ilirjana Hyseni,James M Mchenry,Jessica Faber,Jill V Hunter,Laura L Hollowell,Stephen R Mccauley,Mary E Aitken,Brian D Biekman,Linda Ewing-Cobbs,Hannah M Lindsey

doi:10.3389/fneur.2021.734055

Abstract

Plasticity is often implicated as a reparative mechanism when addressing structural and functional brain development in young children following traumatic brain injury (TBI); however, conventional imaging methods may not capture the complexities of post-trauma development. The present study examined the cingulum bundles and perforant pathways using diffusion tensor imaging (DTI) in 21 children and adolescents (ages 10–18 years) 5–15 years after sustaining early childhood TBI in comparison with 19 demographically-matched typically-developing children. Verbal memory and executive functioning were also evaluated and analyzed in relation to DTI metrics. Beyond the expected direction of quantitative DTI metrics in the TBI group, we also found qualitative differences in the streamline density of both pathways generated from DTI tractography in over half of those with early TBI. These children exhibited hypertrophic cingulum bundles relative to the comparison group, and the number of tract streamlines negatively correlated with age at injury, particularly in the late-developing anterior regions of the cingulum; however, streamline density did not relate to executive functioning. Although streamline density of the perforant pathway was not related to age at injury, streamline density of the left perforant pathway was significantly and positively related to verbal memory scores in those with TBI, and a moderate effect size was found in the right hemisphere. DTI tractography may provide insight into developmental plasticity in children post-injury. While traditional DTI metrics demonstrate expected relations to cognitive performance in group-based analyses, altered growth is reflected in the white matter structures themselves in some children several years post-injury. Whether this plasticity is adaptive or maladaptive, and whether the alterations are structure-specific, warrants further investigation.

Highlights

The concepts of increased vulnerability and neuroplasticity have been used to understand recovery from early traumatic brain injury (TBI), yet the interaction of the timing of brain insult with developmental factors that influence recovery remains unclear [1, 2]
No relationship was found for sex with any cognitive variable in the typically-developing children (TDC) group; sex-related differences were apparent in the TBI group for performance on the color naming (CN), word reading (WR), and IN conditions of the Color-Word Interference Test (CWIT)
Age at evaluation was related to WR performance within the TBI group (r = −0.44, p = 0.047); no other relationships were found for age at evaluation with any cognitive or diffusion tensor imaging (DTI) variables in either group

Summary

Introduction

The concepts of increased vulnerability and neuroplasticity have been used to understand recovery from early traumatic brain injury (TBI), yet the interaction of the timing of brain insult with developmental factors that influence recovery remains unclear [1, 2]. Some have postulated early childhood TBI may critically disrupt subsequent synaptic organization and modify neural network formation, whereas later TBI may have more localized effects [3,4,5]. DAI may affect WM integrity by disrupting neural networks [9], and diffusion tensor imaging (DTI), which is more sensitive to structural alteration in pediatric TBI than conventional MRI [10], is ideally suited to explore potential WM changes related to TBI and age at the time of injury. DTI measures the diffusion of water molecules in brain tissue to interrogate WM integrity or organization via several quantitative diffusion metrics, including fractional anisotropy (FA), a measure of the extent to which diffusion is restricted, and mean diffusivity (MD), a measure of the average rate of diffusion within a voxel [10]. DTI tractography is a quantitative post-processing method by which discrete tract streamlines that model WM pathways are generated [13]

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