• Kartik K Iyer, Andrew Zalesky, Karen M Barlow, and Luca Cocchi.
• Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
• Ann Clin Transl Neurol. 2019 Dec 1; 6 (12): 2544-2554.

ObjectiveTo determine whether anatomical and functional brain features relate to key persistent post-concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS.MethodsOne hundred and ten children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children's Hospital. The primary outcome was the Post-Concussion Symptom Inventory (PCSI, parent proxy). Sleep disturbance scores (PCSI subdomain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks postinjury and 8-10 weeks postinjury. Gray matter volumes were assessed using magnetic resonance imaging (MRI) and voxel-based morphometry at 4 weeks postinjury. Functional connectivity was estimated at the same timepoint using resting-state MRI. Two complementary machine learning methods were used to assess if the combination of gray matter and functional connectivity indices carried meaningful prognostic information.ResultsHigher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in gray matter volume and local functional connectivity in two key nodes of the default mode network: the posterior cingulate cortex and the medial prefrontal cortex. Sleep-related disturbances also significantly correlated with reductions in functional connectivity between these brain regions. The combination of structural and functional brain indices associated to individual variations in the default mode network accurately predicted clinical outcomes at follow-up (area under the curve = 0.86).InterpretationThese results highlight that the function-structure profile of core default mode regions underpins sleep-related problems following mTBI and carries meaningful prognostic information for pediatric concussion recovery.© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

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