Abstract

Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork suggests that mTBI can be conceptualized as a dysconnection syndrome. It remains unclear whether reduced WM integrity is the trigger for changes in cortical surface area or whether tissue deformations are the direct result of mechanical forces acting on the brain. The findings suggest that rapid identification of high-risk patients with the use of clinical scales should be assessed acutely as part of the mTBI protocol.

Highlights

  • Research into mild traumatic brain injury has frequently highlighted difficulties in interpreting results derived from a unique biomarker or neuroimaging technique to explore brain injuries (Shenton et al, 2012; Ling et al, 2013; Dodd et al, 2014)

  • Total Rivermead Post Concussion Symptoms Questionnaire (RPQ) score was significantly higher in the mild traumatic brain injury (mTBI) group than in healthy controls (HC) at 1-week post-injury (Figure 1)

  • We demonstrated that (i) both structural connectivity strength and cortical surface area show a similar potential to serve as a highly sensitive marker for the quantification of brain damage associated with subjective symptoms in acute mTBI patients; (ii) alterations in white matter (WM) and gray matter (GM) are localized in similar brain regions and related to each other; and (iii) the reduction of area seen in frontal regions is correlated with poorer attentive-executive performance in the mTBI group

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Summary

Introduction

Research into mild traumatic brain injury (mTBI) has frequently highlighted difficulties in interpreting results derived from a unique biomarker or neuroimaging technique to explore brain injuries (Shenton et al, 2012; Ling et al, 2013; Dodd et al, 2014). The combination of DTI-based fiber tractography and graph-theoretical network analysis has opened new powerful possibilities to explore the brain’s structural connectome (Hagmann et al, 2008; Bullmore and Sporns, 2009; Hänggi et al, 2014) In this graph-based approach, brain complexity is mapped as a widely distributed network of nodes and edges, representing brain regions and its axonal tracts (Zalesky et al, 2010). In this framework, the strength of the anatomical link between two nodes is measured as the total number of interconnecting fibers. This study with children demonstrated evidence of correlation between symptom severity as assessed by the post-concussion

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