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Front Hum Neurosci. 2016 Mar 29;10:127. doi: 10.3389/fnhum.2016.00127. eCollection 2016.

Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

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Bellikon Rehabilitation ClinicBellikon, Switzerland; Division Neuropsychology, Department of Psychology, University of ZurichZurich, Switzerland.
Bellikon Rehabilitation Clinic Bellikon, Switzerland.
Division of Trauma Surgery, University Hospital Zurich Zurich, Switzerland.
Department of Traumatology, Cantonal Hospital Aarau Aarau, Switzerland.
Department of Neurosurgery, Cantonal Hospital Aarau Aarau, Switzerland.
Interdisciplinary Emergency Centre, Baden Cantonal Hospital Baden, Switzerland.
Department of Surgery, Waid Hospital Zurich Zurich, Switzerland.
Institute of Diagnostic and Interventional Radiology, University Hospital Zurich Zurich, Switzerland.
Brain and Trauma Foundation Grison Chur, Switzerland.
Division Neuropsychology, Department of Psychology, University of ZurichZurich, Switzerland; International Normal Aging and Plasticity Imaging Center, University of ZurichZurich, Switzerland; Center for Integrative Human Physiology, University of ZurichZurich, Switzerland; University Research Priority Program, Dynamic of Healthy Aging, University of ZurichZurich, Switzerland.
Division Neuropsychology, Department of Psychology, University of Zurich Zurich, Switzerland.


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.


connectivity analysis; cortical surface area; mild traumatic brain injury; multimodal MRI; structural connectome; subjective symptoms

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