Default mode network anatomy and function is linked to pediatric concussion recovery

Abstract

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.

Neural correlates of sleep recovery following melatonin treatment for pediatric concussion: a randomized control trial

“…Echo-planar images (rs-fMRI) were collected for five minutes and ten seconds (2000 ms TR, 30 ms TE, 90° flip angle, 3.6 mm slice thickness, 23 × 23 cm FOV, 64 × 64 matrix). As reported elsewhere, 9, 21 pre-processing included regression of nuisance covariates including head motion (Friston 24), linear trends, and signals from cerebrospinal fluid (CSF) and white matter (WM). Our final cohort comprised of a total of 62 subjects, after excluding 6 subjects due to absence of post-treatment scans or failure to pass quality control measures.…”

“… A) Pre-melatonin GM clusters in the PCC (indicated in red, from our previous study 9 ) were identified from whole-brain analyses to be negatively correlated with sleep and fatigue disturbances. The main effect of group of whole-brain GM post-melatonin in this study is also shown (indicated in bright green).…”

“…Neuroimaging analyses were performed within MATLAB (MathWorks, Natick, Massachusetts), using SPM12 and custom scripts. Visualizations for our figures were generated using a combination of MATLAB, MRIcroGL and online tools ( Following earlier work, 9,21 we measured functional connectivity (FC) using two methods. We first examined whole-brain FC using a validated parcellation comprising 214 regions.…”

“…4,5 The neural effects of these ongoing sleep disturbances in TBIs, which include insomnia, pleiosomnia, and fatigue, alongside headaches, dizziness and irritability common to PPCS are associated with changes in brain structure and function during recovery. [6][7][8][9][10][11][12] In examining neural changes during pediatric PPCS recovery, fMRI connectivity studies have highlighted the significance of altered patterns of communications within brain regions comprising the default mode (DMN) and executive networks. [11][12][13][14][15] In typically developing cohorts, sleep-related problems in children and adolescents are known to compromise the efficiency and connectivity of key nodes of the DMN, such as the posterior cingulate cortex (PCC).…”

“…Adding to this literature, we recently reported that, in children with mTBI and PPCS, persisting sleep disturbance and fatigue are linked to decreases in functional connectivity and grey matter volumes within the posterior and anterior regions of the DMN one month following the injury. 9 Given these evidences, the relationship between symptom resolution and brain network reorganization is likely to reveal important insights into the role of neuroplasticity and likelihood for recovery.…”