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

Abstract

Objective:To 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.Methods: 110 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 sub-domain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks post-injury and 8-10 weeks post-injury. Grey matter volumes were assessed using magnetic resonance imaging (MRI) and voxel-based morphometry. Functional connectivity was estimated using resting-state MRI. Two complementary machine learning methods were used to assess if the combination of grey matter and functional connectivity indices carried meaningful prognostic information.Results: Higher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in grey 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). Interpretation:These 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.

Exploring the relationship between resting state intra-network connectivity and accelerometer-measured physical activity in pediatric concussion: A cohort study

“…We demonstrate that intra-network connectivity within the DMN–but not the SMN, SA, or FPN–is associated with accelerometer-measured LPA, MPA, and VPA within the first month of injury in pediatric concussion. Adding to the literature demonstrating associations between DMN impairment and concussion symptoms, depression, anxiety, and sleep-impairment 15,16 , we show that intra-network connectivity within DMN may be implicated with habitual physical activity within the first month of injury in children.…”

A Scoping Review of Magnetic Resonance Modalities Used in Detection of Persistent Postconcussion Symptoms in Pediatric Populations

“…Of the 8 articles, 2 studies 43,69 had participants undergo carbon dioxide stress testing using resting-state blood oxygenation level dependent to assess cerebrovascular responsiveness in youth with PPCS. In the first study, 70 patient-specific differences in PPCS individuals were observed in all participants. Voxel-by-voxel comparison of blood oxygenation level dependent cerebrovascular responsiveness for typically developing controls and PPCS patients showed a significantly greater response in 0.15% of the PPCS group, and significantly less responsiveness in 5.4% of the PPCS group.…”

“…In the second carbon dioxide stress-response study, 43 4 of 6 participants with PPCS demonstrated abnormal alterations in cerebrovascular responsiveness, using second-level analysis comparing youth with PPCS to typically developing control cerebrovascular responsiveness longitudinally. 43 A handful of studies assessed functional connectivity 46,60,67,[70][71][72] with mixed, but mainly significant, findings. In a study by Iyer and colleagues, 70 regional homogeneity (intraregional connectivity) and functional connectivity (interregional connectivity) in the posterior cingulate cortex was negatively correlated with sleep disturbances in individuals with PPCS compared to individuals with recovered concussion.…”

Sex-specific differences in resting-state functional brain activity in pediatric concussion

“…At one-month post-injury (the expected time of recovery 1 ), results of rs-fMRI studies are mixed 13,14,16-18 . With respect to studies of children diagnosed with PCS, one study found that within-network functional connectivity across seven validated brain networks did not differ between children with PCS (n=110) vs. healthy peers (n=20), although select PCS symptoms, sleep impairment, and poorer cognition were associated with connectivity in the concussed cohort 19,20 .…”

“…Some studies involved male only cohorts 14,16,21 , whereas others had less than 25% female representation in their samples 13,17 ; in some cases, data on sex were not reported 18,22 . Only a few studies had samples that approached balance (40-45% female) with respect to sex distribution 15,19,20,23 , though these studies did not stratify their results by sex, instead providing group-level data comparing mixed-sex cohorts of children with concussion to their healthy peers. The most direct data on sex-specific rs-fMRI differences come from a recent study involving adults with PCS 24 .…”