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Background: Digital health technologies are increasingly used by healthcare professionals working in pediatric hospital and rehabilitation settings. Multiple factors may affect the implementation and use of digital health technologies in these settings. However, such factors have not been identified in a multidisciplinary, pediatric context. The objective of this study was to describe actual use and to identify the factors that promote or hinder the intention to use digital health technologies (mobile learning applications, virtual/augmented reality, serious games, robotic devices, telehealth applications, computerized assessment tools, and wearables) among pediatric healthcare professionals., Methods: An online survey evaluating opinions, current use, and future intentions to use digital health technologies was completed by 108 professionals at one of Canada's largest pediatric institutes. Mann-Whitney U tests were used to compare the attitudes of healthcare professionals who intend to increase their use of digital health technologies and those who do not. Linear regression analyses were used to determine predictors of usage success., Results: Healthcare professionals reported mostly using mobile and tablet learning applications (n = 43, 38.1%), telehealth applications (n = 49, 43.4%), and computerized assessment tools (n = 33, 29.2%). Attitudes promoting the intention to increase the use of digital health technologies varied according to technology type. Healthcare professionals who wished to increase their use of digital health technologies reported a more positive attitude regarding benefits in clinical practice and patient care, but were also more critical of potential negative impacts on patient-professional relationships. Ease of use (β = 0.374; p = 0.020) was a significant predictor of more favorable usage success. The range of obstacles encountered was also a significant predictor (β = 0.342; p = 0.032) of less favorable evaluation of usage success. Specific factors that hinder successful usage are lack of training (β = 0.303; p = 0.033) and inadequate infrastructure (β = 0.342; p = 0.032)., Conclusions: When working with children, incorporating digital health technologies can be effective for motivation and adherence. However, it is crucial to ensure these tools are implemented properly. The findings of this study underscore the importance of addressing training and infrastructure needs when elaborating technology-specific strategies for multidisciplinary adoption of digital health technologies in pediatric settings., (© 2024. The Author(s).)

Protective factors, including psychological resilience, cognitive reserve, and brain reserve, may be positively associated with recovery after pediatric mild traumatic brain injury (mTBI) but are yet to be studied concurrently. We sought to examine these factors as moderators of post-concussive symptoms (PCS) in pediatric mTBI compared with mild orthopedic injury (OI). Participants included 967 children (633 mTBI, 334 OI) aged 8-16.99 years, recruited from 5 Canadian pediatric emergency departments as part of a prospective longitudinal cohort study. At 10 days post-injury, psychological resilience was measured using the Connor-Davidson Resilience Scale and brain reserve was measured using total brain volume derived from structural magnetic resonance imaging. Cognitive reserve was measured at 3 months post-injury using IQ scores from the Wechsler Abbreviated Scale of Intelligence-Second Edition. Cognitive and somatic PCS were measured using child and parent ratings on the Health and Behavior Inventory, completed weekly for 3 months and biweekly to 6 months. Analyses involved generalized least-squares regression models using restricted cubic splines. Covariates included age at injury, sex, racialized identity, material and social deprivation, pre-injury migraine and concussion history, and retrospective pre-injury PCS. Psychological resilience moderated group differences in parent-reported PCS. At 30 days post-injury, estimated group differences in parent-reported cognitive and somatic PCS (mTBI > OI) were larger at higher (75th percentile) resilience scores ( Est = 2.25 [0.87, 3.64] and Est = 2.38 [1.76, 3.00], respectively) than at lower (25th percentile) resilience scores ( Est = 1.44 [0.01, 2.86] and Est = 2.08 [1.45, 2.71], respectively). Resilience did not moderate group differences in child-reported PCS but was negatively associated with child-reported PCS in both groups ( p s ≤ 0.001). Brain reserve (i.e., total brain volume [TBV]) also moderated group differences, but only for parent-reported somatic PCS ( p = 0.018). Group difference (mTBI > OI) at 30 days was larger at smaller (25th percentile) TBV ( Est = 2.78 [2.17, 3.38]) than at larger (75th percentile) TBV ( Est = 1.95 [1.31, 2.59]). TBV was not associated with parent-reported cognitive PCS or child-reported PCS. IQ did not moderate PCS in either group but had a significant non-linear association in both groups with child-reported somatic PCS ( p = 0.018) and parent-reported PCS ( p < 0.001), with higher PCS scores at both lower and higher IQs. These findings suggest that higher resilience predicts fewer PCS, but less strongly after mTBI than OI; greater brain reserve may reduce the effect of mTBI on somatic PCS; and cognitive reserve has an unexpected curvilinear association with PCS across injury types. The results highlight the importance of protective factors as predictors of recovery and potential targets for intervention following pediatric mTBI.

Importance: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children., Objective: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure., Design, Setting, and Participants: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. Participants included children aged 6 to 72 months with early childhood concussion or orthopedic injury (OI) or uninjured children from the community to serve as controls. Data were analyzed from March 2023 to January 2024., Exposure: Concussion sustained between ages 6 and 72 months., Main Outcomes and Measures: Primary outcomes were cognitive, physical, behavioral and total PCS assessed prior to injury (retrospectively), acutely (within 48 hours), and at 10 days, 1 month, and 3 months after injury or recruitment through caregiver observations using the Report of Early Childhood Traumatic Injury Observations & Symptoms inventory. Group comparisons were analyzed using ordinal regression models., Results: The study included 303 children (mean [SD] age, 35.8 [20.2] months; 152 [50.2%] male). Of these, 174 children had a concussion (mean [SD] age,  33.3 [19.9] months), 60 children had an OI (mean [SD] age, 38.4 [19.8] months) and 69 children were uninjured controls (mean [SD] age, 39.7 [20.8] months). No meaningful differences were found between the concussion and comparison groups in retrospective preinjury PCS. Significant group differences were found for total PCS at the initial ED visit (concussion vs OI: odds ratio [OR], 4.33 [95% CI, 2.44-7.69]; concussion vs control: OR, 7.28 [95% CI, 3.80-13.93]), 10 days (concussion vs OI: OR, 4.44 [95% CI, 2.17-9.06]; concussion vs control: OR, 5.94 [95% CI, 3.22-10.94]), 1 month (concussion vs OI: OR, 2.70 [95% CI, 1.56-4.68]; concussion vs control: OR, 4.32 [95% CI, 2.36-7.92]), and 3 months (concussion vs OI: OR, 2.61 [95% CI, 1.30-5.25]; concussion vs control: OR, 2.40 [95% CI, 1.36-4.24]). Significant group differences were also found for domain-level scores (cognitive, physical, behavioral) at various time points., Conclusions and Relevance: In this early childhood cohort study, concussion was associated with more PCS than OIs or typical development up to 3 months after injury. Given the limited verbal and cognitive abilities typical of early childhood, using developmentally appropriate manifestations and behaviors is a valuable way of tracking PCS and could aid in concussion diagnosis in young children.

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents ( n  = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Concussion is commonly characterized by a cascade of neurometabolic changes following injury. Magnetic Resonance Spectroscopy (MRS) can be used to quantify neurometabolites non-invasively. Longitudinal changes in neurometabolites have rarely been studied in pediatric concussion, and fewer studies consider symptoms. This study examines longitudinal changes of neurometabolites in pediatric concussion and associations between neurometabolites and symptom burden. Participants who presented with concussion or orthopedic injury (OI, comparison group) were recruited. The first timepoint for MRS data collection was at a mean of 12 days post-injury (n = 545). Participants were then randomized to 3 (n = 243) or 6 (n = 215) months for MRS follow-up. Parents completed symptom questionnaires to quantify somatic and cognitive symptoms at multiple timepoints following injury. There were no significant changes in neurometabolites over time in the concussion group and neurometabolite trajectories did not differ between asymptomatic concussion, symptomatic concussion, and OI groups. Cross-sectionally, Choline was significantly lower in those with persistent somatic symptoms compared to OI controls at 3 months post-injury. Lower Choline was also significantly associated with higher somatic symptoms. Although overall neurometabolites do not change over time, choline differences that appear at 3 months and is related to somatic symptoms., (© 2024. The Author(s).)

Higher psychological resilience is correlated with less severe post-concussion symptoms (PCS) after mild traumatic brain injury (mTBI) in children, but the directional nature of this relationship remains uncertain. Although traditionally regarded as a stable, trait-like construct, resilience may be malleable and potentially influenced by mTBI and post-concussive symptoms. The current study sought to examine the stability of resilience, elucidate the dynamic nature of the resilience-PCS relation, and determine whether resilience-symptom associations are specific to mTBI or applicable to traumatic injury in general. Participants were children aged 8-16.99 years with either mTBI ( n  = 633) or orthopedic injury (OI; n  = 334) recruited to participate in a prospective cohort study after presenting acutely to five Canadian pediatric emergency departments (EDs). Symptoms and psychological resilience were assessed at 1 week, 3 months, and 6 months post-injury. Group differences in resilience over time were examined using a mixed linear model, and associations between resilience and symptoms over time were examined using random intercepts cross-lagged panel modeling (RI-CLPM). The mTBI group reported significantly lower resilience than the OI group, but the difference was significantly larger 1 week post-injury ( d  = 0.50) than at 3 months ( d  = 0.08) and 6 months ( d  = 0.10). Cross-lagged panel models indicated that resilience had both stable and dynamic aspects, and both affected and was affected by PCS, although their association varied by time post-injury, symptom measure, and reporter (parent vs. child). Higher parent-reported cognitive symptom severity at 1 week was significantly associated with higher resilience at 3 months ( β  = 0.23, p  = 0.001). Higher resilience at 3 months was associated with lower levels of parent-reported somatic symptom severity ( β  = -0.14, p  = 0.004) and fewer total symptoms ( β  = -0.135, p  = 0.029) at 6 months. Higher resilience at 3 months was associated with fewer child-reported symptoms at 6 months ( β  = -0.11, p  = 0.030) and, reciprocally, fewer child-reported symptoms at 3 months were associated with higher resilience at 6 months ( β  = -0.22, p  = 0.001). Notably, injury group was not a significant moderator in cross-lagged models, suggesting that resilience-symptom associations are not specific to mTBI. Psychological resilience and symptoms have bidirectional relationships after injury. Interventions designed to foster resilience have the potential to promote recovery after mTBI specifically and injury more generally.

Introduction: Preschoolers and school-aged children with congenital heart disease (CHD) are at higher risk of attention deficit hyperactivity disorder (ADHD) compared with the general population. To this day, no randomised controlled trial (RCT) aiming to improve attention has been conducted in young children with CHD. There is emerging evidence indicating that parent-child yoga interventions improve attention and reduce ADHD symptoms in both typically developing and clinical populations., Methods and Analysis: This is a single-blind, two-centre, two-arm trial during which 24 children with CHD and their parents will be randomly assigned to (1) a parent-child yoga intervention in addition to standard clinical care or (2) standard clinical care alone. All participants will undergo standardised assessments: (1) at baseline, (2) immediately post-treatment and (3) 6 months post-treatment. Descriptive statistics will be used to estimate the feasibility and neurodevelopmental outcomes. This feasibility study will evaluate: (1) recruitment capacity; (2) retention, drop-out and withdrawal rates during the yoga programme and at the 6-month follow-up; (3) adherence to the intervention; (4) acceptability of the randomisation process by families; (5) heterogeneity in the delivery of the intervention between instructors and use of home-based exercises between participants; (6) proportion of missing data in the neurodevelopmental assessments and (7) SD of primary outcomes of the full RCT in order to determine the future appropriate sample size., Ethics and Dissemination: Ethical approval has been obtained by the Research Ethics Board of the Sainte-Justine University Hospital. The findings will be disseminated in peer-reviewed journals and conferences and presented to the Canadian paediatric grand round meetings., Trial Registration Number: NCT05997680., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Socio-emotional skills, including social competence and social cognition, form the basis for robust relationships and wellbeing. Despite their importance, these skills are poorly defined and measured, particularly in children with developmental vulnerabilities. As a consequence, targets for effective management and treatment remain unclear. We aimed to i) phenotype social competence and social cognition in typically developing children (TDC) and in children with neurodevelopmental or mental health disorders (clinical groups) and ii) establish the relationships between these child-direct measures and parent ratings of social competence and behavior., Method: Using a multi-site, cross-sectional study design, we recruited 513 TDC and 136 children with neurodevelopmental (autism spectrum disorder [ASD], attention deficit hyperactivity disorder [ADHD]) or mental health (Anxiety Disorder [ANX]) diagnoses (age range 5-15 years). We administered the Paediatric Evaluation of Emotions, Relationships and Socialisation (PEERS) to children, and parents completed standardised questionnaires rating children's socio-emotional function., Results: Standardised parent questionnaires revealed a global pattern of everyday socio-emotional impairment that was common to all clinical groups, while PEERS identified disorder-specific socio-cognitive profiles for children with ASD, ADHD and ANX. Compared to TDCs, children with ASD demonstrated global socio-cognitive impairment. Children with ADHD were impulsive, demonstrating difficulties managing speed accuracy trade-offs. Children with ANX exhibited slowed social decision-making, but otherwise intact skills., Conclusions: Standardized parent questionnaires of child socio-emotional function reveal differences between children with typical and atypical development, but do not yield disorder-specific, socio-emotional profiles. In contrast, findings from the PEERS objective assessment suggest that that ASD, ADHD and ANX are associated with distinct socio-cognitive phenotypes, to more accurately guide and target management and treatment of impaired social competence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Anderson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion ( n = 360; 56% male) or mild orthopaedic injury ( n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: The effects caused by differences in data acquisition can be substantial and may impact data interpretation in multi-site/scanner studies using magnetic resonance spectroscopy (MRS). Given the increasing use of multi-site studies, a better understanding of how to account for different scanners is needed. Using data from a concussion population, we compare ComBat harmonization with different statistical methods in controlling for site, vendor, and scanner as covariates to determine how to best control for multi-site data., Methods: The data for the current study included 545 MRS datasets to measure tNAA, tCr, tCho, Glx, and mI to study the pediatric concussion acquired across five sites, six scanners, and two different MRI vendors. For each metabolite, the site and vendor were accounted for in seven different models of general linear models (GLM) or mixed-effects models while testing for group differences between the concussion and orthopedic injury. Models 1 and 2 controlled for vendor and site. Models 3 and 4 controlled for scanner. Models 5 and 6 controlled for site applied to data harmonized by vendor using ComBat. Model 7 controlled for scanner applied to data harmonized by scanner using ComBat. All the models controlled for age and sex as covariates., Results: Models 1 and 2, controlling for site and vendor, showed no significant group effect in any metabolites, but the vendor and site were significant factors in the GLM. Model 3, which included a scanner, showed a significant group effect for tNAA and tCho, and the scanner was a significant factor. Model 4, controlling for the scanner, did not show a group effect in the mixed model. The data harmonized by the vendor using ComBat (Models 5 and 6) had no significant group effect in both the GLM and mixed models. Lastly, the data harmonized by the scanner using ComBat (Model 7) showed no significant group effect. The individual site data suggest there were no group differences., Conclusion: Using data from a large clinical concussion population, different analysis techniques to control for site, vendor, and scanner in MRS data yielded different results. The findings support the use of ComBat harmonization for clinical MRS data, as it removes the site and vendor effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor HZ declared a past co-authorship with the author AH., (Copyright © 2023 La, Bell, Craig, Doan, Beauchamp, Zemek, Yeates and Harris.)

Millions of children sustain a concussion annually. Concussion disrupts cellular signaling and neural pathways within the brain but the resulting metabolic disruptions are not well characterized. Magnetic resonance spectroscopy (MRS) can examine key brain metabolites (e.g., N-acetyl Aspartate (tNAA), glutamate (Glx), creatine (tCr), choline (tCho), and myo-Inositol (mI)) to better understand these disruptions. In this study, we used MRS to examine differences in brain metabolites between children and adolescents with concussion versus orthopedic injury. Children and adolescents with concussion (n = 361) or orthopedic injury (OI) (n = 184) aged 8 to 17 years were recruited from five emergency departments across Canada. MRS data were collected from the left dorsolateral prefrontal cortex (L-DLPFC) using point resolved spectroscopy (PRESS) at 3 T at a mean of 12 days post-injury (median 10 days post-injury, range 2-33 days). Univariate analyses for each metabolite found no statistically significant metabolite differences between groups. Within each analysis, several covariates were statistically significant. Follow-up analyses designed to account for possible confounding factors including age, site, scanner, vendor, time since injury, and tissue type (and interactions as appropriate) did not find any metabolite group differences. In the largest sample of pediatric concussion studied with MRS to date, we found no metabolite differences between concussion and OI groups in the L-DLPFC. We suggest that at 2 weeks post-injury in a general pediatric concussion population, brain metabolites in the L-DLPFC are not specifically affected by brain injury., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d  = 0.44), cognitive fatigue (Cohen d  = 0.59), sleep/rest fatigue (Cohen d  = 0.37), and total fatigue (Cohen d  = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.

Objectives: To measure the association between psychosocial problems and persistent post-concussive symptoms (PCS) in youth who were seen in the emergency department with mild traumatic brain injury (mTBI) or orthopedic injury (OI)., Methods: From a larger prospective cohort study, Advancing Concussion Assessment in Pediatrics (A-CAP), 122 child-guardian pairs who presented to the emergency department with mTBI (N = 70) or OI (N = 52) were recruited for this cross-sectional sub-study. Each pair completed 2 measures assessing PCS burden at 2 weeks, 3 months, and 6 months post-injury. At one visit, pairs concurrently completed MyHEARTSMAP, a comprehensive, psychosocial self-assessment tool to evaluate 4 domains of mental wellness., Results: When measured at the same visit, children who self-reported moderate or severe Psychiatry domain concerns concurrently experienced a greater burden of cognitive symptoms (β = 5.49; 0.93-10.05) and higher overall PCS count (β = 2.59; 0.70-4.48) after adjusting for covariables, including retrospective pre-injury symptoms and injury group. Additionally, reports indicating mild Function domain severity were associated with increased cognitive (β = 3.34; 95% CI: 0.69-5.99) and somatic symptoms (β = 6.79; 2.15-11.42) and total symptom count (β = 1.29; 0.18-2.39)., Conclusion: Increasing severity in multiple domains of mental health is associated with more PCS in youth. While the differences in PCS between the mTBI and OI groups appeared somewhat larger for children with more mental health concerns, the interaction was not statistically significant; larger sample sizes are needed to evaluate the moderating effect of psychosocial difficulties on post-concussion symptoms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adequate social functioning during childhood requires context-appropriate social decision-making. To make such decisions, children rely on their social norms, conceptualized as cognitive models of shared expectations. Since social norms are dynamic, children must adapt their models of shared expectations and modify their behavior in line with their social environment. This study aimed to investigate children's abilities to use social information to adapt their fairness norm and to identify the computational mechanism governing this process. Thirty children (7-11 years, M = 7.9 SD = 0.85, 11 girls) played the role of Responder in a modified version of the Ultimatum Game-a two-player game based on the fairness norm-in which they had to choose to accept or reject offers from different Proposers. Norm adaptation was assessed by comparing rejection rates before and after a conditioning block in which children received several low offers. Computational models were compared to test which best explains children's behavior during the game. Mean rejection rate decreased significantly after receiving several low offers suggesting that children have the ability to dynamically update their fairness norm and adapt to changing social environments. Model-based analyses suggest that this process involves the computation of norm-prediction errors. This is the first study on norm adaptation capacities in school-aged children that uses a computational approach. Children use implicit social information to adapt their fairness norm to changing environments and this process appears to be supported by a computational mechanism in which norm-prediction errors are used to update norms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Morasse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Demographic and environmental factors can affect child recovery after traumatic brain injury (TBI); however, little is known about their role in predicting child perceptions of competence (i.e., subjective judgments of ability or a sense of adequacy)., Objectives: This prospective, cohort study examined the contribution of participant sex, age at assessment, socioeconomic status, parent-reported change in academic performance post-injury, and the quality of a child's relationship with their family (i.e., family affective involvement, intimacy, integration, and the nature of family roles) to child perceptions of global and academic competence 12 months after pediatric TBI., Methods: Participants included 127 children, 84 with a TBI (53 mild, 31 moderate-severe TBI; injury age: 5-15 years) and 43 age-matched typically developing (TD) controls. Children rated their perceptions of global and academic competence and degree of family intimacy and integration. Parents completed questionnaires measuring socioeconomic status, family affective involvement, and the nature of family roles. Parents also indicated whether they perceived a change in their child's post-injury academic performance., Results: Child perceptions of academic competence were significantly lower for children with moderate-severe TBI relative to TD children. In contrast, child perceptions of global competence were comparable between TBI and TD control groups. Socioeconomic status, age at assessment, parent-reported relative change in academic performance post-TBI, and family roles were associated with child perceptions of academic competence. Degree of family integration was the sole predictor of child perceptions of global competence., Conclusions: Child perceptions of academic competence are vulnerable to the effects of moderate-severe TBI, particularly among older children and those from low socioeconomic backgrounds. Well-defined family roles and greater integration of family units might enhance perceptions of global and academic competence in children with TBI., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Sociomoral reasoning (SMR) is an essential component of social functioning allowing children to establish judgments based on moral criteria. The progressive emergence and complexification of SMR during childhood is thought to be underpinned by a range of characteristics and abilities present in the preschool years. Past studies have mostly examined concurrent associations between individual factors and SMR. Using a more comprehensive and predictive approach to identify early predictors of school-age SMR would contribute to a more complete picture of SMR development. This study aimed to investigate the contribution of four domains of preschool predictors to SMR at school-age: demographic (age, sex, parental education), cognitive (executive and sociocognitive functions), behavioral (internalizing and externalizing behaviors), and familial (parent-child interactions, parental stress) factors. Parents of 122 children 3 to 5 years (M = 3.70, SD = 0.66 years, 51% girls) completed questionnaires and children were administered executive and sociocognitive tasks. Parent-child interactions were assessed using an observational approach. SMR was measured four years later using the SoMoral task. A four-step hierarchical regression analysis revealed that executive functions and internalizing problems were significant independent predictors of SMR. These findings provide a more comprehensive understanding of the early precursors of SMR during childhood.

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre-injury and 1-month post-injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion-weighted imaging at post-acute (2-33 days post-injury) and chronic (3 or 6 months via random assignment) post-injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, -0.58 (-1.04, -0.11), and superior longitudinal fasciculus, -0.49 (-0.90, -0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post-injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To (1) determine the level of agreement between symptom provocation and performance-based tests of vestibulo-ocular reflex (VOR) function after pediatric mild traumatic brain injury (mTBI) and (2) describe the level of symptom provocation induced by a VOR task in individuals with and without cervical findings., Design: Cross-sectional., Setting: This study was conducted at a tertiary care pediatric hospital., Participants: A total of 101 participants (N=101) aged 6-18 years within 3 weeks of mTBI diagnosis were included (54.5% female; mean age, 13.92±2.63 years; mean time since injury at assessment, 18.26±6.16 days)., Interventions: None., Main Outcome Measures: Symptom provocation (Vestibular/Ocular Motor Screening tool), performance (clinician-observed VOR performance, head thrust test [HTT], computerized dynamic visual acuity test, video head impulse test), and c ervical impairment (cervical flexion-rotation test, range of motion test, self-reported neck pain). Agreement was evaluated using Cohen's κ statistic., Results: No outcomes demonstrated agreement with symptom provocation (κ=-0.15 to 0.14). Fair agreement demonstrated between clinician-observed VOR performance and HTT (κ=0.32), with little to no agreement demonstrated between other measures. Proportions reporting test-induced dizziness and headache were greater among individuals with cervical findings (29.1%-41.8%) than without (2.3%-6.8%)., Conclusions: Findings support that symptom provocation and performance-based tests measure different constructs and thus have distinct roles when assessing VOR function. Findings suggest results from measures of symptom provocation may be influenced by coexisting cervical impairments, underlining the value of assessing for cervical injury after pediatric mTBI., (© 2022 The Authors.)

Background: Impairments to oculomotor (OM) and vestibulo-ocular reflex (VOR) function following pediatric mTBI have been demonstrated but are poorly understood. Such impairments can be associated with more negative prognosis, affecting physical and mental wellbeing, emphasizing the need to more fully understand how these evolve., Objectives: to determine i) the extent to which performance on clinical and computerized tests of OM and VOR function varies over time in children and adolescents at 21 days, 3-, and 6-months post-mTBI; ii) the proportion of children and adolescents with mTBI presenting with abnormal scores on these tests at each timepoint., Design: Prospective longitudinal design., Setting: Tertiary care pediatric hospital., Participants: 36 participants with mTBI aged 6 to18., Procedures: Participants were assessed on a battery of OM and VOR tests within 21 days, at 3- and 6-months post injury., Outcome Measures: Clinical measures : Vestibular/ocular motor screening tool (VOMS) (symptom provocation and performance); Computerized measures: reflexive saccade test (response latency) , video head impulse test (VOR gain), and dynamic visual acuity test (LogMAR change)., Analysis: Generalized estimating equations (parameter estimates and odd ratios) estimated the effect of time. Proportions above and below normal cut-off values were determined., Results: Our sample consisted of 52.8% females [mean age 13.98 (2.4) years, assessed on average 19.07 (8-33) days post-injury]. Older children performed better on visual motion sensitivity (OR 1.43, p = 0.03) and female participants worse on near point of convergence (OR 0.19, p = 0.03). Change over time (toward recovery) was demonstrated by VOMS overall symptom provocation (OR 9.90, p = 0.012), vertical smooth pursuit (OR 4.04, p = 0.03), voluntary saccade performance (OR 6.06, p = 0.005) and right VOR gain (0.068, p = 0.013). Version performance and VOR symptom provocation showed high abnormal proportions at initial assessment., Discussion: Results indicate impairments to the VOR pathway may be present and driving symptom provocation. Vertical smooth pursuit and saccade findings underline the need to include these tasks in test batteries to comprehensively assess the integrity of OM and vestibular systems post-mTBI., Implications: Findings demonstrate 1) added value in including symptom and performance-based measures in when OM and VOR assessments; 2) the relative stability of constructs measured beyond 3 months post mTBI., (Copyright © 2022 Crampton, Schneider, Grilli, Chevignard, Katz-Leurer, Beauchamp, Debert and Gagnon.)

The analysis of large, multisite neuroimaging datasets provides a promising means for robust characterization of brain networks that can reduce false positives and improve reproducibility. However, the use of different MRI scanners introduces variability to the data. Managing those sources of variability is increasingly important for the generation of accurate group-level inferences. ComBat is one of the most promising tools for multisite (multiscanner) harmonization of structural neuroimaging data, but no study has examined its application to graph theory metrics derived from the structural brain connectome. The present work evaluates the use of ComBat for multisite harmonization in the context of structural network analysis of diffusion-weighted scans from the Advancing Concussion Assessment in Pediatrics (A-CAP) study. Scans were acquired on six different scanners from 484 children aged 8.00-16.99 years [Mean = 12.37 ± 2.34 years; 289 (59.7%) Male] ~10 days following mild traumatic brain injury ( n = 313) or orthopedic injury ( n = 171). Whole brain deterministic diffusion tensor tractography was conducted and used to construct a 90 x 90 weighted (average fractional anisotropy) adjacency matrix for each scan. ComBat harmonization was applied separately at one of two different stages during data processing, either on the (i) weighted adjacency matrices (matrix harmonization) or (ii) global network metrics derived using unharmonized weighted adjacency matrices (parameter harmonization). Global network metrics based on unharmonized adjacency matrices and each harmonization approach were derived. Robust scanner effects were found for unharmonized metrics. Some scanner effects remained significant for matrix harmonized metrics, but effect sizes were less robust. Parameter harmonized metrics did not differ by scanner. Intraclass correlations (ICC) indicated good to excellent within-scanner consistency between metrics calculated before and after both harmonization approaches. Age correlated with unharmonized network metrics, but was more strongly correlated with network metrics based on both harmonization approaches. Parameter harmonization successfully controlled for scanner variability while preserving network topology and connectivity weights, indicating that harmonization of global network parameters based on unharmonized adjacency matrices may provide optimal results. The current work supports the use of ComBat for removing multiscanner effects on global network topology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Onicas, Ware, Harris, Beauchamp, Beaulieu, Craig, Doan, Freedman, Goodyear, Zemek, Yeates and Lebel.)

Sophisticated network-based approaches such as structural connectomics may help to detect a biomarker of mild traumatic brain injury (mTBI) in children. This study compared the structural connectome of children with mTBI or mild orthopedic injury (OI) to that of typically developing (TD) children. Children aged 8-16.99 years with mTBI (n = 83) or OI (n = 37) were recruited from the emergency department and completed 3T diffusion MRI 2-20 days postinjury. TD children (n = 39) were recruited from the community and completed diffusion MRI. Graph theory metrics were calculated for the binarized average fractional anisotropy among 90 regions. Multivariable linear regression and linear mixed effects models were used to compare groups, with covariates age, hemisphere, and sex, correcting for multiple comparisons. The two injury groups did not differ on graph theory metrics, but both differed from TD children in global metrics (local network efficiency: TD > OI, mTBI, d = 0.49; clustering coefficient: TD < OI, mTBI, d = 0.49) and regional metrics for the fusiform gyrus (lower degree centrality and nodal efficiency: TD > OI, mTBI, d = 0.80 to 0.96; characteristic path length: TD < OI, mTBI, d = -0.75 to -0.90) and in the superior and middle orbital frontal gyrus, paracentral lobule, insula, and thalamus (clustering coefficient: TD > OI, mTBI, d = 0.66 to 0.68). Both mTBI and OI demonstrated reduced global and regional network efficiency and segregation as compared to TD children. Findings suggest a general effect of childhood injury that could reflect pre- and postinjury factors that can alter brain structure. An OI group provides a more conservative comparison group than TD children for structural neuroimaging research in pediatric mTBI., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Social cognition and competence are a key part of daily interactions and essential for satisfying relationships and well-being. Pediatric neurological and psychological conditions can affect social cognition and require assessment and remediation of social skills. To adequately approximate the complex and dynamic nature of real-world social interactions, innovative tools are needed. The aim of this study was to document the performance of adolescents on two versions of a serious video game presenting realistic, everyday, socio-moral conflicts, and to explore whether their performance is associated with empathy or sense of presence, factors known to influence social cognition., Methods: Participants (12-17 years, M = 14.39; SD = 1.35) first completed a pre-test measure of socio-moral reasoning based on three dilemmas from a previously validated computer task. Then, they either played an evaluative version ( n = 24) or an adaptive ( n = 33) version of a video game presenting nine social situations in which they made socio-moral decisions and provided justifications. In the evaluative version, participants' audio justifications were recorded verbatim and coded manually to obtain a socio-moral reasoning maturity score. In the adaptive version (AV), tailored feedback and social reinforcements were provided based on participant responses. An automatic coding algorithm developed using artificial intelligence was used to determine socio-moral maturity level in real-time and to provide a basis for the feedback and reinforcements in the game. All participants then completed a three-dilemma post-test assessment., Results: Those who played the adaptive version showed improved SMR across the pre-test, in-game and post-test moral maturity scores, F (1.97,63.00) = 9.81, p HF < 0.001, ϵ 2 = 0.21, but those who played the Evaluative version did not. Socio-moral reasoning scores from both versions combined did not correlate with empathy or sense of presence during the game, though results neared significance. The study findings support preliminary validation of the game as a promising method for assessing and remediating social skills during adolescence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zarglayoun, Laurendeau-Martin, Tato, Vera-Estay, Blondin, Lamy-Brunelle, Chaieb, Morasse, Dufresne, Nkambou and Beauchamp.)

Background: Mild traumatic brain injury (mTBI) is associated with persistent post-concussive symptoms (PCSs) in approximately 15% of cases. These symptoms can be somatic (e.g., headache), cognitive (e.g., forgetfulness, poor attention and concentration capacities), emotional (e.g., anxiety, depression, irritability) and/or sleep-arousal complaints (e.g., fatigue, sleep problems). Although practice guidelines recommend early intervention to prevent and treat PCS, we still lack an effective, standardized, integrative, post-acute intervention based on a sound and validated theoretical model., Objectives: The purpose of this article is to present the development and theoretical background underpinning a novel intervention for patients with PCSs in the post-acute phase after mTBI (1-3 months post-injury)., Procedure: With a biopsychosocial approach (Hou et al., 2012) and best practice recommendations, we developed a novel multidimensional intervention targeting factors that perpetuate PCSs and that can be changed with the intervention. This individual-session intervention provides practical tools for managing PCSs and is designed to provide psycho-education and reassurance, reinforce individual objectives and promote a return to activities. Each session targets one category of PCSs: Sleep/fatigue, Attention, Anxiety/depressed mood, Memory/Organization (SAAM intervention). The rationale underlying the choices of format and content for the intervention is discussed, as are the associated strengths, limitations, opportunities and challenges., Conclusion: This article could support researchers and clinicians to develop, replicate and/or implement interventions addressing current best practices in mTBI management., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The identification of children with traumatic brain injury (TBI) who are at risk of death or poor global neurological functional outcome remains a challenge. Magnetic resonance imaging (MRI) can detect several brain pathologies that are a result of TBI; however, the types and locations of pathology that are the most predictive remain to be determined. Forty-two critically ill children with TBI were recruited prospectively from pediatric intensive care units at five Canadian children's hospitals. Pathologies detected on subacute phase MRIs included cerebral hematoma, herniation, cerebral laceration, cerebral edema, midline shift, and the presence and location of cerebral contusion or diffuse axonal injury (DAI) in 28 regions of interest were assessed. Global functional outcome or death more than 12 months post-injury was assessed using the Pediatric Cerebral Performance Category score. Linear modeling was employed to evaluate the utility of an MRI composite score for predicting long-term global neurological function or death after injury, and nonlinear Random Forest modeling was used to identify which MRI features have the most predictive utility. A linear predictive model of favorable versus unfavorable long-term outcomes was significantly improved when an MRI composite score was added to clinical variables. Nonlinear Random Forest modeling identified five MRI variables as stable predictors of poor outcomes: presence of herniation, DAI in the parietal lobe, DAI in the subcortical white matter, DAI in the posterior corpus callosum, and cerebral contusion in the anterior temporal lobe. Clinical MRI has prognostic value to identify children with TBI at risk of long-term unfavorable outcomes.

Despite many children experiencing fatigue after childhood brain injury, little is known about the predictors of this complaint. To date, traditional indices of traumatic brain injury (TBI) severity have not predicted reliably persisting fatigue (up to three years post-injury). This study aimed to establish whether persisting fatigue is predicted by serum biomarker concentrations in child TBI. We examined whether acute serum biomarker expression would improve prediction models of 12-month fatigue based on injury severity. Blood samples were collected from 87 children (1-17 years at injury) sustaining mild to severe TBI (Glasgow Coma Scale [GCS] range 3-15; mean 12.43; classified as mild TBI [ n  = 50, 57%] vs. moderate/severe TBI [ n  = 37, 43%]), and presenting to the emergency departments (ED) and pediatric intensive care units (PICU) at one of three tertiary pediatric hospitals (Royal Children's Hospital (RCH); Hospital for Sick Children (HSC), Toronto; St Justine Children's Hospital (SJH), Montreal). Six serum biomarker concentrations were measured within 24 h of injury (interleukin-6, interleukin-8 [IL-8], soluble vascular cell adhesion molecule [SVCAM], S100 calcium binding protein B [S100B], neuron specific enolase [NSE], and soluble neural cell adhesion molecule [sNCAM]). Fatigue at 12 months post-injury was measured using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (parent report), classified as present/absent using previously derived cut-points. At 12 months post-injury, 22% of participants experienced fatigue. A model including IL-8 was the best serum biomarker for estimating the probability of children experiencing fatigue at 12 months post-injury. The IL-8 also significantly improved predictive models of fatigue based on severity.

Although childhood traumatic brain injury (TBI) has been linked to heightened risk of impaired social skills and behavior, current evidence is weakened by small studies of variable methodological quality. To address these weaknesses, this international multi-cohort study involved synthesis of data from two large observational cohort studies of complicated mild-severe child TBI in Australia and North America. Both studies adopted a unified approach to data collection and coding procedures, providing the opportunity to merge datasets from multiple, well-characterized cohorts for which gold standard measures of social outcomes were collected during the chronic recovery phase. The study involved 218 children, including 33 children with severe TBI, 83 children with complicated mild-moderate TBI, 59 children with orthopedic injury, and 43 age- and sex-matched typically developing control children. All injured children were recruited from academic children's hospitals and underwent direct cognitive assessments including measures of theory of mind (ToM) at least 1-year post- injury. Parents rated their child's social adjustment using standardized measures of social skills, communication and behavior. Results showed a brain-injury specific effect on ToM abilities, such that children with both complicated mild to moderate and severe TBI displayed significantly poorer ToM than children without TBI. In mediator models, poorer ToM predicted poorer parent-rated self-direction and social skills, as well as more frequent behavioral symptoms. The ToM mediated the effect of severe TBI on parent ratings of communication and social skills, as well as on overall behavior symptoms. The findings suggest that deficits in ToM are evident across the spectrum of TBI severity and represent one mechanism linking severe child TBI to long-term social adjustment difficulties. The findings underscore the value of large-scale data harmonization projects to increase the quality of evidence regarding the outcomes of TBI. Clinical and scientific implications are discussed.

Background: Pediatric mild traumatic brain injury (mTBI) affects millions of children annually. Diffusion tensor imaging (DTI) is sensitive to axonal injuries and white matter microstructure and has been used to characterize the brain changes associated with mild traumatic brain injury (mTBI). Neurite orientation dispersion and density imaging (NODDI) is a diffusion model that can provide additional insight beyond traditional DTI metrics, but has not been examined in pediatric mTBI. The goal of this study was to employ DTI and NODDI to gain added insight into white matter alterations in children with mTBI compared to children with mild orthopedic injury (OI)., Methods: Children (mTBI n = 320, OI n = 176) aged 8-16.99 years (12.39 ± 2.32 years) were recruited from emergency departments at five hospitals across Canada and underwent 3 T MRI on average 11 days post-injury. DTI and NODDI metrics were calculated for seven major white matter tracts and compared between groups using univariate analysis of covariance controlling for age, sex, and scanner type. False discovery rate (FDR) was used to correct for multiple comparisons., Results: Univariate analysis revealed no significant group main effects or interactions in DTI or NODDI metrics. Fractional anisotropy and neurite density index in all tracts exhibited a significant positive association with age and mean diffusivity in all tracts exhibited a significant negative association with age in the whole sample., Conclusions: Overall, there were no significant differences between mTBI and OI groups in brain white matter microstructure from either DTI or NODDI in the seven tracts. This indicates that mTBI is associated with relatively minor white matter differences, if any, at the post-acute stage. Brain differences may evolve at later stages of injury, so longitudinal studies with long-term follow-up are needed., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pediatric traumatic brain injury (TBI) can lead to adverse emotional, social, and behavioral consequences. However, outcome is difficult to predict due to significant individual variability, likely reflecting a complex interaction between injury- and child-related variables. Among these variables are genetically determined individual differences, which can modulate TBI outcome through their influence on neuroplasticity mechanisms. In this study, we examined the effect of Val66Met, a common polymorphism of the brain-derived neurotrophic factor gene known to be involved in neuroplasticity mechanisms, on behavioral symptoms of mild TBI (mTBI) sustained in early childhood. This work is part of a prospective, longitudinal cohort study of early TBI. The current sample consisted of 145 children between ages 18 and 60 months assigned to one of three participant groups: mild TBI, orthopedic injury, or typically developing children. Participants provided a saliva sample to detect the presence of the Val66Met polymorphism, and the Child Behavior Checklist was used to document the presence of behavioral symptoms at 6- and 18-months post-injury. Contrary to our initial hypothesis, at 6 months post-injury, non-carriers of the Val66Met polymorphism in the mTBI group presented significantly more internalizing symptoms (e.g., anxiety/depression and somatic complaints) than Val66Met carriers, who were similar to orthopedically injured and typically developing children. However, at 18 months post-injury, all children with mTBI presented more internalizing symptoms, independent of genotype. The results of the study provide evidence for a protective effect of the Val66Met polymorphism on internalizing behavior symptoms 6 months after early childhood mTBI.

Introduction: Mild traumatic brain injury (mTBI) is highly prevalent, especially in children under 6 years. However, little research focuses on the consequences of mTBI early in development. The objective of the Kids' Outcomes And Long-term Abilities (KOALA) study is to document the impact of early mTBI on children's motor, cognitive, social and behavioural functioning, as well as on quality of life, stress, sleep and brain integrity., Methods and Analyses: KOALA is a prospective, multicentre, longitudinal cohort study of children aged 6 months to 6 years at the time of injury/recruitment. Children who sustain mTBI (n=150) or an orthopaedic injury (n=75) will be recruited from three paediatric emergency departments (PEDs), and compared with typically developing children (community controls, n=75). A comprehensive battery of prognostic and outcome measures will be collected in the PED, at 10 days, 1, 3 and 12 months postinjury. Biological measures, including measures of brain structure and function (magnetic resonance imaging, MRI), stress (hair cortisol), sleep (actigraphy) and genetics (saliva), will complement direct testing of function using developmental and neuropsychological measures and parent questionnaires. Group comparisons and predictive models will test the a priori hypotheses that, compared with children from the community or with orthopaedic injuries, children with mTBI will (1) display more postconcussive symptoms and exhibit poorer motor, cognitive, social and behavioural functioning; (2) show evidence of altered brain structure and function, poorer sleep and higher levels of stress hormones. A combination of child, injury, socioenvironmental and psychobiological factors are expected to predict behaviour and quality of life at 1, 3 and 12 months postinjury., Ethics and Dissemination: The KOALA study is approved by the Sainte-Justine University Hospital, McGill University Health Centre and University of Calgary Conjoint Health Research Ethics Boards. Parents of participants will provide written consent. Dissemination will occur through peer-reviewed journals and an integrated knowledge translation plan., Competing Interests: Competing interests: CL’s spouse is an employee of General Electric Healthcare. The other authors report no biomedical financial interests or potential conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injury (TBI) in childhood and adolescence can interrupt expected development, compromise the integrity of the social brain network (SBN) and impact social skills. Yet, no study has investigated functional alterations of the SBN following pediatric TBI. This study explored functional connectivity within the SBN following TBI in two independent adolescent samples. First, 14 adolescents with mild complex, moderate or severe TBI and 16 typically developing controls (TDC) underwent resting-state functional magnetic resonance imaging 12-24 months post-injury. Region of interest analyses were conducted to compare the groups' functional connectivity using selected SBN seeds. Then, replicative analysis was performed in an independent sample of adolescents with similar characteristics (9 TBI, 9 TDC). Results were adjusted for age, sex, socioeconomic status and total gray matter volume, and corrected for multiple comparisons. Significant between-group differences were detected for functional connectivity in the dorsomedial prefrontal cortex and left fusiform gyrus, and between the left fusiform gyrus and left superior frontal gyrus, indicating positive functional connectivity for the TBI group (negative for TDC). The replication study revealed group differences in the same direction between the left superior frontal gyrus and right fusiform gyrus. This study indicates that pediatric TBI may alter functional connectivity of the social brain. Frontal-fusiform connectivity has previously been shown to support affect recognition and changes in the function of this network could relate to more effortful processing and broad social impairments., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Objective: To document longitudinal changes in internalizing and externalizing behavioral symptoms after mild traumatic brain injury (mTBI) sustained in early childhood (i.e., between 18 and 60 months of age)., Methods: Participants (N = 226) were recruited to one of three groups: children with mTBI, typically developing children and orthopedic injured children. The Child Behavior Checklist was used to document the presence of internalizing and externalizing behaviors at 6, 18, and 30 months postinjury. Linear mixed-model analyses were used to examine group effects on the trajectory of internalizing and externalizing behavioral manifestations over 30 months postinjury., Results: Children who sustain mTBI during the preschool period have higher rates of internalizing and externalizing behavioral symptoms at the initial assessment time point and these symptoms persist up to 30 months postinjury. Moreover, results indicate that for up to 18 months postinjury, significantly more children with mTBI present behavioral difficulties that may require some form of clinical attention (i.e., scores in the borderline or clinical range), than do their orthopedically injured and noninjured peers., Conclusions: Sustaining mTBI early in life may lead to long-lasting behavioral changes in young children (i.e., at least 30 months). These changes are likely the product of a complex interplay between neurological and non-neurological factors, both contributing to generating and maintaining behavioral difficulties., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Social dysfunction is a common and disabling outcome of childhood traumatic brain injury (TBI); however, the mechanisms that link early brain injury to impaired social behavior are unclear. This longitudinal prospective study involved 129 children, including 86 children with TBI (53 mild, 33 moderate-severe TBI) and 43 age-matched typically developing control (TDC) children. Children with TBI were recruited via consecutive admissions to the emergency department of the Royal Children's Hospital, Melbourne Australia. At 6 months post-injury, all participants were assessed on measures of intellectual functioning, and parents provided ratings of children's self-regulation skills using gold standard measures of everyday executive function. At 12-month follow up, parents rated children's social adjustment using standardized measures of social skills, communication, and behavior. As expected, children with moderate-severe TBI were rated by parents as having greater self-regulation problems, worse social skills, and poorer communication than the mild TBI and TDC groups. In mediation models, greater self-regulation problems at 6 months post-injury were predictive of poorer social skills and worse overall social adjustment at 12-month follow-up. Moreover, self-regulation skills mediated the effect of moderate-severe TBI, but not mild TBI, on social skills and overall social adjustment. Our findings show that, while impaired social adjustment is common at 12 months following moderate-severe child TBI, the impact of TBI on these outcomes is likely mediated by its effect on self-regulation skills. Evidence for robust prospective associations between self-regulation deficits and later social adjustment difficulties have implications for early identification of children at high risk for chronic social problems.

Given the lack of evidence regarding effective pharmacological and non-pharmacological interventions for pediatric mild traumatic brain injury (mTBI) and the resultant lack of treatment recommendations reflected in consensus guidelines, variation in the management of pediatric mTBI is to be expected. We therefore surveyed practitioners across 15 centers in the United States and Canada who care for children with pediatric mTBI to evaluate common-practice variation in the management of pediatric mTBI. The survey, developed by a panel of pediatric mTBI experts, consisted of a 10-item survey instrument regarding providers' perception of common pediatric mTBI symptoms and mTBI interventions. Surveys were distributed electronically to a convenience sample of local experts at each center. Frequencies and percentages (with confidence intervals [CI]) were determined for survey responses. One hundred and seven respondents (71% response rate) included specialists in pediatric Emergency Medicine, Sports Medicine, Neurology, Neurosurgery, Neuropsychology, Neuropsychiatry, Physical and Occupational Therapy, Physiatry/Rehabilitation, and General Pediatrics. Respondents rated headache as the most prevalently reported symptom after pediatric mTBI, followed by cognitive problems, dizziness, and irritability. Of the 65 (61%; [95% CI: 51,70]) respondents able to prescribe medications, non-steroidal anti-inflammatory medications (55%; [95% CI: 42,68]) and acetaminophen (59%; [95% CI: 46,71]) were most commonly recommended. One in five respondents reported prescribing amitriptyline for headache management after pediatric mTBI, whereas topiramate (8%; [95% CI: 3,17]) was less commonly reported. For cognitive problems, methylphenidate (11%; [95% CI: 4,21]) was used more commonly than amantadine (2%; [95% CI: 0,8]). The most common non-pharmacological interventions were rest ("always" or "often" recommended by 83% [95% CI: 63,92] of the 107 respondents), exercise (59%; [95%CI: 49,69]), vestibular therapy (42% [95%CI: 33,53]) and cervical spine exercises (29% [95%CI: 21,39]). Self-reported utilization for common pediatric mTBI interventions varied widely across our Canadian and United States consortium. Future effectiveness studies for pediatric mTBI are urgently needed to advance the evidence-based care.

The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. This substudy included 2323 children from the original cohort ages 8.00-17.99 years who had data for at least 80% of all variables included in each LCA. Concussion was defined according to Zurich consensus statement diagnostic criteria. The primary outcome was PPCS at 4 and 12 weeks after enrollment. Participants were 39.5% female and had a mean age of 12.8 years (standard deviation = 2.6). Follow-up was completed by 1980 (85%) at 4 weeks and 1744 (75%) at 12 weeks. LCA identified four groups with discrete pre-injury histories, four groups with discrete clinical presentations, and seven groups with discrete profiles of acute symptoms. Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.

Objective: Ondansetron is increasingly administered to children suffering from concussion-associated nausea/vomiting. We examined the association between ondansetron administration and post-concussion symptoms in children at 1 week and 1 month following the concussion., Methods: This was a secondary analysis of data collected prospectively in a cohort study conducted in nine pediatric emergency departments (EDs) (5P study). Participants were children ages between 5 and 17.99 years who sustained a concussion in the previous 48 hours. For the current study, only 5P participants who reported nausea and/or vomiting in the ED were eligible. The exposure of interest was ondansetron administration; the comparison group included all other participants. The primary outcome was an increase in at least three symptoms of the Post-Concussion Symptom Inventory score at 1 week and 1 month following trauma., Results: Among the 3,063 children included in the 5P study, 1805 (59%) reported nausea and provided data at 1 week and/or 1 month. Among them, 132 (7%) received ondansetron. Multivariable logistic regression adjusted for confounders did not show an association between ondansetron use and the risk of persistent post-concussion symptoms at 1 week (OR: 1.13 [95% CI: 0.86-1.49]), but it was associated with a higher risk at 1 month (OR: 1.33 [95% CI: 1.05-1.97])., Conclusion: In children presenting to the ED with an acute concussion, ondansetron use was associated with a higher risk of persistent post-concussion symptoms at 1 month. Although this may be related to the limitations of the design, it highlights the importance of evaluating this association using a randomized clinical trial.

A significant proportion of children and adolescents report psychological distress following concussion, but little is known about the predictors of these problems. The purpose of this study was to examine predictive factors of psychological distress following pediatric concussion. It was hypothesized that the presence of pre-injury psychological distress would be the strongest predictor of psychological distress post-concussion, with other demographic and acute injury factors adding incrementally to prediction. This is a prospective, multi-center cohort. Children and adolescents (6-17 years old; n = 311) who sustained a concussion and were assessed through four pediatric emergency departments. Participants were reassessed at 4-weeks (n = 275) and 12-weeks (n = 190) post-injury. Emergency department (ED) assessment documented injury mechanism, acute symptomatology, acute cognitive functioning, and pre-injury functioning. Psychological distress at 4- and 12-weeks follow-up was categorized as present if one or more psychological scores from the parent-completed measures (Child Behavior Checklist, Strengths and Difficulties Questionnaire) exceeded established cutoffs. The presence of psychological distress at each follow-up was predicted using multi-variable logistic regressions. Psychological distress was reported in 23% of youth at both 4- and 12-weeks post-concussion. A pre-injury diagnosis of anxiety and acutely forgetting recent information were significant predictors of psychological distress at 4 weeks, whereas worse acute orientation assessment in the ED predicted psychological distress at 12 weeks. Nearly one of four youth experienced psychological distress after concussion. Clinicians in acute care settings should screen for the factors (pre-injury anxiety, acute mental status) associated with post-injury psychological distress and consider proactively referring patients for further assistance.

Infants' experiences are considered to determine to a large degree the strength and effectiveness of neural connections and fine tune the development of brain networks. As one of the most pervasive and potent relational experiences of infancy, parent-child relationships appear to be prime candidates to account for experience-driven differences in children's brain development. Yet, studies linking parenting and functional connectivity are surprisingly scarce, and restricted to the connectivity of limbic structures. Accordingly, this longitudinal study explored whether normative variation in the quality of early maternal behaviour predicts the functional connectivity of large-scale brain networks in late childhood. Maternal mind-mindedness and autonomy support were assessed with 28 children when they were 13 and 15 months old respectively. When children were 10 years of age, children underwent a resting-state functional MRI exam. Functional connectivity was assessed between key regions of the default mode network (DMN), salience network (SN), and frontal-parietal central executive network (CEN). Results revealed that higher mind-mindedness and autonomy support predicted stronger negative connectivity between DMN and SN regions. These findings are the first to provide preliminary evidence suggestive of a long-lasting impact of variation within the normative range of early maternal behaviour on functional connectivity between large-scale brain networks., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eye-tracking studies suggest that visual encoding is important for social processes such as socio-moral reasoning. Alterations to the visual encoding of faces, for example, have been linked to the social phenotype of autism spectrum disorders (ASDs) and are associated with social and communication impairments. Yet, people with ASD often perform similarly to neurotypical participants on measures of moral reasoning, supporting the hypothesis of differential mechanisms of moral reasoning in ASD. The objective of this study was to document visual encoding and moral reasoning in ASD and neurotypical individuals using a visual, ecological, sociomoral reasoning paradigm paired with eye-tracking. Two groups (ASD, Control) matched for age and IQ completed the SoMoral task, a set of picture situations describing everyday moral dilemmas, while their eye movements and pupil dilation were recorded. Moral understanding, decision-making, and justification were recorded. Participants with ASD presented a longer time to first fixation on faces. They also understood fewer dilemmas and produced fewer socially adaptive responses. Despite a similar average level of moral maturity, the justifications produced by participants with ASD were not distributed in the same way as the neurotypical participants. Visual encoding was a significant predictor of moral decision-making and moral justification for both groups. The results are discussed in the context of alternative mechanisms of moral reasoning in ASD.

A critical component for accelerating the clinical uptake of research data in the area of pediatric concussion or mild traumatic brain injury (MTBI) pertains to the establishment and utilization of common databases. The objective of the first phase of our CanPedCDE initiative was to agree upon pediatric common data elements (CDEs) that could best characterize children with MTBI over their recovery period. The selection of CDEs for our framework aimed to balance factors such as the comprehensiveness of outcomes collected, their applicability to diverse settings, as well as the costs associated with their use. Selection began by identifying relevant domains of functioning (e.g., post-concussion symptoms, attention, and balance). Two sources were used to make this process more efficient: 1) the World Health Organization International Classification of Functioning (ICF) Traumatic Brain Injury Core Set, and the U.S. National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Common Data Elements, both of which had already suggested relevant domains to include in TBI research. The process was completed in two phases: 1) using an online survey of experts and 2) through an in-person consensus meeting. Measurement tools were also proposed that were best felt to capture these domains. Forty experts in MTBI in children from multiple health-related perspectives (e.g., emergency medicine, pediatrics, neurosurgery, nursing, physiotherapy, and neuroscience), as well as knowledge users, participated in the selection process. The final list of CDEs included 77 distinct areas of functioning, covering all categories of the ICF model. Outcome measures were attached to each element, when applicable. The CanPedCDE initiative addresses a significant limitation in MTBI research to date and may help both researchers and clinicians to organize and standardize their assessment of children and youth post-MTBI in order to move the field in promising directions.

As the first step of social information processing, visual encoding underlies the interpretation of social cues. Faces, in particular, convey a large amount of affective information, which can be subsequently used in the planning and production of adaptive social behaviors. Sociomoral reasoning is a specific social skill that is associated with engagement in appropriate social behaviors when faced with dilemmas. Previous studies using eye tracking suggest that visual encoding may play an important role in decision-making when individuals are faced with extreme moral dilemmas, but it is not known if this is generalizable to everyday situations. The main objective of this study was to assess the contribution of visual encoding to everyday sociomoral reasoning using eye tracking and ecological visual dilemmas. Participants completed the SocioMoral Reasoning Aptitude Level (SoMoral) task while their eye movements and pupil dilation were recorded. While visual encoding was not a predictor of sociomoral decision-making, sociomoral maturity was predicted by fixation count. Thus, in an ecological context, visual encoding of social cues appears to be associated with sociomoral maturity: the production of a justification is associated with volitional encoding strategies. Implications with regards to the dual-process theory of sociomoral reasoning and social information processing are discussed., Competing Interests: The authors have declared that no competing interests exist.

Background: Attention deficits are common after pediatric Traumatic Brain Injury (TBI); they complicate return to activities of daily living and disrupt socioacademic reintegration. Yet, clinicians in rehabilitation settings have limited access to cognitive remediation protocols for which feasibility has been demonstrated., Objective: The aim of this study was to evaluate the feasibility of intensive attention process training program Ready! Set? Let's Train! (RST), based on an adaptation of the Attention Process Training-I program., Materials and Methods: In a randomized controlled trial, participants with attention deficits were assigned to receive the attention process training intervention (RST) or Homework Assistance (HWA). Pre- and post-intervention assessments consisted of standardized attentional and executive tests and a behavior checklist., Results: Analyses conducted for 17 participants (RST, n=8; HWA, n=9; mean age 14.70±2.17 years, 11 males) indicated the study was successful in that it showed improvements in working memory (F(14)=5.44, P=0.04; η 2 =0.19), inhibition (F(14)=10.18, P=0.007; η 2 =0.75) and cognitive flexibility (F(14)=5.36, P=0.04; η 2 =0.57)., Conclusions: These findings indicate positive support for combined process-specific and metacognitive strategy training for attention and executive functions., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Humans are by nature a social species, with much of human experience spent in social interaction. Unsurprisingly, social functioning is crucial to well-being and quality of life across the lifespan. While early intervention for social problems appears promising, our ability to identify the specific impairments underlying their social problems (eg, social communication) is restricted by a dearth of accurate, ecologically valid and comprehensive child-direct assessment tools. Current tools are largely limited to parent and teacher ratings scales, which may identify social dysfunction, but not its underlying cause, or adult-based experimental tools, which lack age-appropriate norms. The present study describes the development and standardisation of Paediatric Evaluation of Emotions, Relationships, and Socialisation ( PEERS®), an iPad-based social skills assessment tool., Methods: The PEERS project is a cross-sectional study involving two groups: (1) a normative group, recruited from early childhood, primary and secondary schools across metropolitan and regional Victoria, Australia; and (2) a clinical group, ascertained from outpatient services at The Royal Children's Hospital Melbourne (RCH). The project aims to establish normative data for PEERS®, a novel and comprehensive app-delivered child-direct measure of social skills for children and youth. The project involves recruiting and assessing 1000 children aged 4.0-17.11 years. Assessments consist of an intellectual screen, PEERS® subtests, and PEERS-Q, a self-report questionnaire of social skills. Parents and teachers also complete questionnaires relating to participants' social skills. Main analyses will comprise regression-based continuous norming, factor analysis and psychometric analysis of PEERS® and PEERS-Q., Ethics and Dissemination: Ethics approval has been obtained through the RCH Human Research Ethics Committee (34046), the Victorian Government Department of Education and Early Childhood Development (002318), and Catholic Education Melbourne (2166). Findings will be disseminated through international conferences and peer-reviewed journals. Following standardisation of PEERS®, the tool will be made commercially available., Competing Interests: Competing interests: The authors would like to declare that although the PEERS app was intended to be a freely available research tool at the commencement of its design, it is now likely to be a commercial product. VA, MHB, GC, DD, JJD, SJD, MJ, SMD, FM and LT all declare a pending patent on the PEERS app. GC and MJ declare fees received from the Murdoch Children’s Research Institute for services rendered in the development of the PEERS app. VA, SJD, FM and LT report grants from the National Health and Medical Research Council for the present study. DD reports fees received from The Royal Children’s Hospital., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A large body of longitudinal research provides compelling evidence for the critical role of early attachment relationships in children's social, emotional, and cognitive development. It is expected that parent-child attachment relationships may also impact children's brain development, however, studies linking normative caregiving experiences and brain structure are scarce. To our knowledge, no study has yet examined the associations between the quality of parent-infant attachment relationships and brain morphology during childhood. The aim of this preliminary study was to investigate the prospective links between mother-infant attachment security and whole-brain gray matter (GM) volume and thickness in late childhood. Attachment security toward the mother was assessed in 33 children when they were 15 months old. These children were then invited to undergo structural magnetic resonance imaging at 10-11 years of age. Results indicated that children more securely attached to their mother in infancy had larger GM volumes in the superior temporal sulcus and gyrus, temporo-parietal junction, and precentral gyrus in late childhood. No associations between attachment security and cortical thickness were found. If replicated, these results would suggest that a secure attachment relationship and its main features (e.g., adequate dyadic emotion regulation, competent exploration) may influence GM volume in brain regions involved in social, cognitive, and emotional functioning through experience-dependent processes.

Objectives: Assess the feasibility of a study evaluating one dose of oral ondansetron to decrease post-concussion symptoms at one week and one month following concussion in children aged 8 to 17 years old., Method: This was a pilot study for a randomized, triple-blind controlled trial of one dose of either ondansetron or placebo performed in a tertiary care pediatric emergency department. Participants were children aged 8 to 17 years who sustained a concussion in the previous 24 hours and visited a single emergency department. The outcome of interest was an increase from pre-concussion baseline of at least 3 symptoms from the Post-Concussion Symptom Inventory, measured at one week and at one month following concussion. The primary outcome was to determine the proportion of children who completed the assessment at one week following the intervention. Secondary outcome was the proportion of children who completed the assessment at one month following the intervention. All children, care givers, and those assessing the outcomes were blinded to the group assignment., Results: Of the 218 children presenting with a concussion during the study period, we screened 108 and found 36/108 (33%) eligible to participate and 16/108 (14.8%) agreed to participate. All enrolled patients were compliant with the intervention and follow-up., Conclusion: In our study population, approximately one-third of the screened concussion patients were eligible to participate and approximately one half of those eligible agreed to participate. Our study found that most enrolled patients preferred electronic follow-up; the noncompliance rate was minimal.

Pediatric traumatic brain injury (TBI) research depends on comparisons of profiles and outcomes between brain-injured individuals and groups consisting either of injured controls (e.g., orthopedic injuries, OI) or uninjured, typically developing children recruited from the community (community controls, CC). Children with OI are thought to provide optimal comparisons for individuals with TBI because they share injury-related experiences and pre-morbid characteristics; however, a study by Mathias and colleagues (2013) 1 in adults has called into question the added value of injury control groups in TBI research. The comparability of these control groups has not been established in young children. Seventy-two children with OI and 84 CC aged between 18 and 60 months were compared on a range of demographic variables, developmental and medical history, pre-injury behavioral and adaptive profiles, as well as on measures of adaptive functioning, behavior, family functioning, post-concussive symptoms, and cognition (intellectual functioning, verbal abilities, executive functioning, social cognition) 6 months after the OI. There were no statistically significant differences between the OI and CC groups on any of the variables tested, whether they related to pre-injury or post-injury characteristics. The findings are applicable to studies seeking to identify appropriate control groups in the context of preschool TBI research, and suggest no clear advantage in recruiting OI controls based on the variables studied and the methodology used. However, further work is necessary to verify additional factors and outcomes relevant to pediatric TBI research, as well as to compare outcomes between these two groups at more acute stages (i.e., prior to 6 months post-injury).

Deficits in theory of mind (ToM) are common after neurological insult acquired in the first and second decade of life, however the contribution of large-scale neural networks to ToM deficits in children with brain injury is unclear. Using paediatric traumatic brain injury (TBI) as a model, this study investigated the sub-acute effect of paediatric traumatic brain injury on grey-matter volume of three large-scale, domain-general brain networks (the Default Mode Network, DMN; the Central Executive Network, CEN; and the Salience Network, SN), as well as two domain-specific neural networks implicated in social-affective processes (the Cerebro-Cerebellar Mentalizing Network, CCMN and the Mirror Neuron/Empathy Network, MNEN). We also evaluated prospective structure-function relationships between these large-scale neural networks and cognitive, affective and conative ToM. 3D T1- weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children [TBI: n = 103; typically developing (TD) children: n = 34]. All children were assessed on measures of ToM at 24-months post-injury. Children with severe TBI showed sub-acute volumetric reductions in the CCMN, SN, MNEN, CEN and DMN, as well as reduced grey-matter volumes of several hub regions of these neural networks. Volumetric reductions in the CCMN and several of its hub regions, including the cerebellum, predicted poorer cognitive ToM. In contrast, poorer affective and conative ToM were predicted by volumetric reductions in the SN and MNEN, respectively. Overall, results suggest that cognitive, affective and conative ToM may be prospectively predicted by individual differences in structure of different neural systems-the CCMN, SN and MNEN, respectively. The prospective relationship between cerebellar volume and cognitive ToM outcomes is a novel finding in our paediatric brain injury sample and suggests that the cerebellum may play a role in the neural networks important for ToM. These findings are discussed in relation to neurocognitive models of ToM. We conclude that detection of sub-acute volumetric abnormalities of large-scale neural networks and their hub regions may aid in the early identification of children at risk for chronic social-cognitive impairment., (© The Author (2017). Published by Oxford University Press.)

Children with traumatic brain injury (TBI) are at risk for social impairment, but research has yet to document the trajectory of these skills post-injury and factors that may predict social problems. This study addressed these gaps in knowledge, reporting on findings from a prospective, longitudinal follow-up study that investigated social outcomes post-injury and explored factors contributing to these outcomes at two years post-injury. The sample included 113 children, 74 with TBI and 39 typically developing (TD) controls. TBI participants were recruited on presentation to the hospital. Parents rated pre-injury function at that time, and all children underwent magnetic resonance imaging (MRI). Participants were followed up at two years post-injury. Outcomes were social adjustment, social participation, social relationships, and social cognition. Predictors of social outcomes examined included brain lesion characteristics, child cognition (6 months post-TBI), and behavior and environmental factors (pre-injury and two years). Reduced social adjustment (p = 0.011) and social participation (p < 0.001) were evident in children with TBI compared with TD controls. Poor social adjustment was predicted by externalizing behavior problems and younger age at injury. Reduced social participation was linked to internalizing behavior problems. Greater lesion volume, lower socioeconomic status, and family burden contributed to poorer social relationships, whereas age at injury predicted social cognition. Within the TBI group, 23% of children exhibited social impairments. Younger age at injury, greater pre-injury, and current behavior problems and family dysfunction, and poorer intelligence quotient (IQ), processing speed, and empathy were linked to impairment. Further follow-up is required to track social recovery and the influences of cognition, brain, and environment over time.

Dyslexia and Attention deficit disorder (AD) are prevalent neurodevelopmental conditions in children and adolescents. They have high comorbidity rates and have both been associated with motor difficulties. Little is known, however, about what is shared or differentiated in dyslexia and AD in terms of motor abilities. Even when motor skill problems are identified, few studies have used the same measurement tools, resulting in inconstant findings. The present study assessed increasingly complex gross motor skills in children and adolescents with dyslexia, AD, and with both Dyslexia and AD. Our results suggest normal performance on simple motor-speed tests, whereas all three groups share a common impairment on unimanual and bimanual sequential motor tasks. Children in these groups generally improve with practice to the same level as normal subjects, though they make more errors. In addition, children with AD are the most impaired on complex bimanual out-of-phase movements and with manual dexterity. These latter findings are examined in light of the Multiple Deficit Model.