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Longitudinal Brain Network Functional Connectivity Changes in Pediatric Concussion: An A-CAP Study
Stephanie Deighton, Department of Psychology, University of Calgary, Calgary, Canada
Keith Yeates, Department of Psychology, University of Calgary, Calgary, Canada
Signe Bray, Department of Radiology, University of Calgary, Calgary, Canada
Kirk Graff, Department of Radiology, University of Calgary, Calgary, Canada
Nishard Abdeen, Department of Radiology, University of Ottawa, Ottawa, Canada
Miriam Beauchamp, Department of Psychology, University of Montreal and CHU Sainte-Justine Hospital Research Center, Montréal, Canada
Christian Beaulieu, Department of Biomedical Engineering, University of Alberta, Edmonton, Canada
Bruce Bjornson, Division of Neurology, Department of Pediatrics, University of British Columbia, Vancouver, Canada
William Craig, University of Alberta and Stollery Children’s Hospital, Edmonton, Canada
Mathieu Dehaes, Department of Radiology, Radio-oncology and Nuclear Medicine, Institute of Biomedical Engineering University of Montreal, Montréal, Canada
Sylvain Deschenes, CHU Sainte-Justine Hospital Research Center, Department of Radiology, Radio-oncology and Nuclear Medicine, Montréal, Canada
Quynh Doan, Department of Pediatrics, University of British Columbia, BC Children’s Hospital Research Institute, Vancouver, Canada
Stephen Freedman, Department of Pediatric and Emergency Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
Bradley Goodyear, Department of Radiology, University of Calgary, Calgary, Canada
Jocelyn Gravel, Department of Pediatric Emergency Medicine, CHU Sainte-Justine, Université de Montréal, Montréal, Canada
Catherine Lebel, Department of Radiology, University of Calgary, Calgary, Canada
Andrée Ledoux, Department of Cellular and Molecular Medicine University of Ottawa and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada
Roger Zemek, Department of Pediatric Emergency Medicine, CHU Sainte-Justine, Université de Montréal, Montréal, Canada
Ashley Ware, Department of Psychology, Georgia State University, Atlanta, United States
Advanced MRI techniques can detect changes in brain structure and function following pediatric mild traumatic brain injury (i.e., concussion). However, functional connectivity (FC) is poorly understood in pediatric concussion. This study addressed the impact of concussion and other demographic variables on FC in children.
A total of 967 children (age 8-16.99 years) with concussion or mild orthopedic injury (OI) were recruited from pediatric emergency departments within 48h post-injury. Pre-injury and 1-month post-injury symptom rating scores were used to classify concussion with (concussion+) or without (concussion-) persisting symptoms 1-month post-injury based on reliable change. Children completed a post-acute (2-33 days) and/or chronic (3 or 6 months via random assignment) MRI, including resting-state functional MRI (rs-fMRI). Following robust quality assurance procedures, FC was computed using Pearson correlation across regions within and between 8 networks from 918 rs-fMRI scans in 585 children (386 concussion/199 OI). Multiple linear mixed-effects models were performed to compare FC between the groups across time post-injury, with age at injury and biological sex treated as moderators and participant as a random effect, with multiple comparison correction.
No post-acute between-group differences were observed. Relative to OI, global FC was reduced 6 months after concussion in males [Cohen’s d (95% confidence interval) = -0.85 (-1.32, -0.38). This effect was seen in both males with concussion+ [-0.94 (-1.79, -0.09)] and concussion- [-0.74 (-1.23, -0.25)] based on parent report. Within-network FC did not differ between groups. Time post-injury moderated group differences in FC between the visual (VIS) and default mode (DMN) networks, which was lower 6 months after concussion relative to OI [-0.54 (-0.87, -0.22)]. Group differences in FC between the ventral attention (VAT) and frontoparietal (FPN) networks were moderated by time and age at injury. Relative to OI, FC was lower 3 months after concussion in younger [-0.88 (-1.49, -0.28)], but higher in older children [0.83 (0.22, 1.44)]. Time and sex moderated group differences in FC between the FPN and DMN, which was higher 6 months after concussion relative to OI in females [0.72 (0.19, 1.26)], but lower in males [-0.61 (-1.06, -0.16)]. Differences in FC between the dorsal attention network (DAN) and VAT among symptom groups based on parent report were moderated by time and sex, whereby FC was higher 3 months post-injury in females with concussion- relative to concussion+ [1.27 (-2.06, -0.47)] and OI [0.88 (0.27, 1.50)].
This study demonstrated global and between-network FC alterations 3- and 6-months following concussion as compared with mild OI in children, including FC changes between networks involved in attention, executive functioning, salience, self-referential, and visual processing. Group differences were moderated by symptom persistence at 1-month post-injury, time post-injury, biological sex, and age at injury, underscoring the need to contextualize pediatric concussion within a comprehensive biopsychosocial framework. The lack of post-acute between-group differences suggests that FC offers limited diagnostic and prognostic utility. Overall, pediatric concussion appears to preserve communication within functional networks while altering it between networks several months post-injury, after most children have typically recovered.
Keyword 1: neuroimaging: functional connectivity
Keyword 2: brain injury
Keyword 3: child brain injury