Postconcussive Symptoms After Early Childhood Concussion.

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.

Factors associated with mathematical capacity in children with Developmental Coordination Disorder.

BACKGROUND: Developmental Coordination Disorder (DCD) is a condition characterized by difficulties in motor planning and coordination and affects 5 to 6% of all school-aged children. Children with DCD frequently present with difficulties with academic activities such as handwriting. However, no study to date has comprehensively described mathematical capacity and its potential associated factors in this high-risk group. AIMS: We aimed to describe the frequency and nature of mathematical difficulties of school-aged children with DCD and to evaluate potential factors associated with mathematical performance. METHODS: A total of 55 elementary school-aged children with DCD underwent comprehensive standardized assessments of mathematical, visuoperceptual (VP), attentional, visual-motor integration (VMI), and motor skills. The contribution of each factor to mathematical capacity was established using hierarchical multivariate linear regression models. RESULTS: Children with DCD (9.1 ± 1.5 years, 44 males) had lower overall mathematical capacity compared to normative data (-0.59 SD) on the KeyMath 3rd edition, with poorer performance in basic concepts and problem-solving. Thirty-eight percent of the sample performed below the 15th percentile in overall mathematical skills. VP skills were the most important factors associated with most mathematical domains. Thirty-four percent of the variance of overall mathematical capacity was explained by VP skills, inattention, VMI and motor impairments while controlling for household income (F [5,49]=5.029, p < .0001). CONCLUSION: Children with DCD present with mathematical difficulties in basic concepts and problem-solving, which are partially explained by VP skills. Our findings stress the important of systematically assessing mathematical difficulties children with DCD to ensure they receive the necessary support that leads to academic success.

Do preinjury life events moderate the outcomes of mild traumatic brain injuries in children? An A-CAP Study.

OBJECTIVE: To examine preinjury life events as moderators of postconcussive symptoms (PCS) and quality of life (QoL) in children with pediatric mild traumatic brain injury (mTBI) versus orthopedic injury (OI). METHODS: Participants were 633 children with mTBI and 334 with OI, ages 8-16.99, recruited from 5 pediatric emergency departments and followed for 6 months postinjury as part of a prospective cohort study. Preinjury life events were measured retrospectively using the Child and Adolescent Survey of Experiences, PCS using the Health and Behavior Inventory (HBI) and Post-Concussion Symptom Interview (PCS-I), and QoL using the Pediatric Quality of Life Inventory (PedsQL). Analyses involved longitudinal regression using restricted cubic splines, with group, positive and negative life events, and time as primary predictors. Covariates included age, sex, race, socioeconomic status, preinjury history (i.e., headache, migraine, previous concussion), and parent-rated retrospective PCS-I, HBI, and PedsQL scores. RESULTS: PCS and QoL were worse after mTBI than OI, but group differences declined with time (all p < .001). Group differences in PCS were larger at higher levels of positive life events, which predicted lower PCS (p= .03 to p < .001) and higher QoL (p = .048) after OI but not after mTBI. Negative life events predicted worse PCS and QoL in both groups (p = .002 to p < .001). CONCLUSIONS: Preinjury positive life events moderate outcomes after pediatric injury, with a protective effect seen in OI but not in mTBI. Negative life events are consistently associated with worse outcomes regardless of injury type.

Longitudinal changes in brain metabolites following pediatric concussion.

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.

Further recommendations of the International Paediatric Brain Injury Society (IPBIS) for the post-acute rehabilitation of children with acquired brain injury.

BACKGROUND: Paediatric acquired brain injury is a life-long condition which impacts on all facets of the individual's lived experience. The existing evidence base continues to expand and new fields of enquiry are established as clinicians and researchers uncover the extent of these impacts. PRIMARY OBJECTIVE: To add to recommendations described in the International Paediatric Brain Injury Society's 2016 paper on post-acute care for children with acquired brain injury and highlight new areas of enquiry. REVIEW OF INFORMATION: Recommendations were made based on the opinions of a group of experienced international clinicians and researchers who are current or past members of the board of directors of the International Paediatric Brain Injury Society. The importance of each recommendation was agreed upon by means of group consensus. OUTCOMES: This update gives new consideration to areas of study including injuries which occur in pre-school children, young people in the military, medical referral, young offenders and the use of technology in rehabilitation.

The association between symptom burden and processing speed and executive functioning at 4 and 12 weeks following pediatric concussion.

OBJECTIVES: Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association. METHODS: This prospective, multicenter cohort study included participants aged 5.00-17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates. RESULTS: 311 children (65.0% males; median age = 11.92 [IQR = 9.14-14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17. CONCLUSIONS: Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

Dynamic Relations Between Psychological Resilience and Post-Concussion Symptoms in Children With Mild Traumatic Brain Injury Versus Orthopedic Injury: An A-CAP Study.

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 (ß = 0.23, p = 0.001). Higher resilience at 3 months was associated with lower levels of parent-reported somatic symptom severity (ß = -0.14, p = 0.004) and fewer total symptoms (ß = -0.135, p = 0.029) at 6 months. Higher resilience at 3 months was associated with fewer child-reported symptoms at 6 months (ß = -0.11, p = 0.030) and, reciprocally, fewer child-reported symptoms at 3 months were associated with higher resilience at 6 months (ß = -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.

Longitudinal Functional Connectome in Pediatric Concussion: An Advancing Concussion Assessment in Pediatrics Study.

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.

A Parent-child yoga intervention for reducing attention deficits in children with congenital heart disease: the Yoga for Little Hearts Feasibility Study Protocol.

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.

Deep phenotyping of socio-emotional skills in children with typical development, neurodevelopmental disorders, and mental health conditions: Evidence from the PEERS.

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.

Prospective associations between maternal mind-mindedness, child theory of mind, and brain morphology in school-aged children.

Mentalizing is defined as the ability to attribute mental states to oneself and others. In the context of parental behavior, parents' tendency to comment on their child's mental activities refers to the concept of mind-mindedness (MM). MM has been positively associated with various developmental outcomes in children, notably their own ability to mentalize, known as theory of mind (ToM). Although parental (MM) and child (ToM) mentalizing have important implications during childhood, their associations with children's neural structures are largely unknown. Among 62 mother-child dyads, maternal MM was rated from free-play sequences when children were aged 1 year, child ToM was assessed using a first-order false-belief task at 4 years of age, and structural MRI images were acquired at 10 years of age. Maternal MM was positively associated with gray matter volumes (GMV) in the dorsal prefrontal cortex and the superior temporal pole. Child ToM abilities were positively associated with GMV in the ventromedial prefrontal cortex. Though cortical regions associated with MM and ToM showed no anatomical overlap, many are functionally connected through a neural network highly involved in self-referential strategies for mentalizing. These findings suggest that MM and ToM may contribute to distinct sub-processes that collectively support social cognition development.

Improving outcome after paediatric concussion: challenges and possibilities.

The term concussion has permeated mainstream media and household vocabulary mainly due to awareness regarding the risks of concussion in professional contact sports, yet it occurs across a variety of settings and ages. Concussion is prevalent in infants, preschoolers, children, and adolescents, and is a common presentation or reason for referral to primary care providers, emergency departments, and specialised trauma clinics. Its broad range of symptoms and sequelae vary according to multiple individual, environmental, and clinical factors and can lead to health and economic burden. More than 20 years of research into risk factors and consequences of paediatric concussion has revealed as many questions as answers, and scientific work and clinical cases continue to expose its complexity and heterogeneity. In this Review, we present empirical evidence for improving outcome after paediatric concussion. We consider work pertaining to both sports and other injury mechanisms to provide a perspective that should be viewed as complementary to publications focused specifically on sports concussion. Contemporary challenges in prevention, diagnosis, prognosis, and intervention are discussed alongside pathways and future directions for improving outcome.

"What If?": Caregivers' Experiences Following Early Childhood Concussion.

OBJECTIVE: Little is known about the symptoms, signs, and management guidelines for children under the age of 6 years after they sustain a concussion. Caregivers of such young children may have unique concerns and encounter different challenges from those of school-age children given the distinctive developmental characteristics of the early childhood period. This study aimed to explore the experience of caregivers through semistructured interviews to inform clinical practice. METHODS: Fifty caregivers of children aged 6 months to 5.99 years were interviewed 3 months postinjury for this qualitative study to document their experience in relation to their child's accident, recovery, and healthcare provisions. RESULTS: Four main themes were identified: (1) visible changes associated with caregiver concerns, (2) a roller-coaster of emotions after the injury, (3) healthcare providers' role in addressing the need for reassurance, and (4) the need for better information after the injury. CONCLUSION: The findings provide critical insight into the unique experiences and information needs of caregivers of young children who sustain concussion. The challenges identified can inform healthcare professionals regarding the needs of caregivers after early concussion and contribute to building a knowledge base for the development of age-appropriate anticipatory guidance for caregiver mental health and child recovery.

IQ After Pediatric Concussion.

OBJECTIVES: This study investigated IQ scores in pediatric concussion (ie, mild traumatic brain injury) versus orthopedic injury. METHODS: Children (N = 866; aged 8-16.99 years) were recruited for 2 prospective cohort studies from emergency departments at children's hospitals (2 sites in the United States and 5 in Canada) ≤48 hours after sustaining a concussion or orthopedic injury. They completed IQ and performance validity testing postacutely (3-18 days postinjury; United States) or 3 months postinjury (Canada). Group differences in IQ scores were examined using 3 complementary statistical approaches (linear modeling, Bayesian, and multigroup factor analysis) in children performing above cutoffs on validity testing. RESULTS: Linear models showed small group differences in full-scale IQ (d [95% confidence interval] = 0.13 [0.00-0.26]) and matrix reasoning (0.16 [0.03-0.30]), but not in vocabulary scores. IQ scores were not related to previous concussion, acute clinical features, injury mechanism, a validated clinical risk score, pre- or postinjury symptom ratings, litigation, or symptomatic status at 1 month postinjury. Bayesian models provided moderate to very strong evidence against group differences in IQ scores (Bayes factor 0.02-0.23). Multigroup factor analysis further demonstrated strict measurement invariance, indicating group equivalence in factor structure of the IQ test and latent variable means. CONCLUSIONS: Across multisite, prospective study cohorts, 3 complementary statistical models provided no evidence of clinically meaningful differences in IQ scores after pediatric concussion. Instead, overall results provided strong evidence against reduced intelligence in the first few weeks to months after pediatric concussion.

Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an Advancing Concussion Assessment in Paediatrics study.

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.

Longitudinal Gray Matter Trajectories in Pediatric Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI). METHODS: Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction. RESULTS: Groups (N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children (d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01]). DISCUSSION: These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework.

Adolescents and Social Media: Longitudinal Links Between Types of Use, Problematic Use and Internalizing Symptoms.

Studies examining the associations between adolescent social media use and depression/anxiety symptoms show inconsistent results and do not elucidate the direction of associations. Differences in how studies operationalize social media use and consider potential moderating effects of sex and extraversion could contribute to inconsistencies. A distinction has been made between three types of social media use: passive, active and problematic. This study examined longitudinal associations between these types of adolescents' social media use and depression/anxiety symptoms and moderation effects of sex or extraversion. At ages 13 (T1) and 14 (T2), 257 adolescents completed an online questionnaire regarding their depression and anxiety symptoms and problematic social media use as well as three social media use diaries. Cross-lagged panel modeling (CLPM) revealed a positive association between problematic use and later anxiety symptoms (ß = .16, p = .010). Extraversion moderated the association between active use and anxiety (ß = -.14, p = .032). Specifically, active use predicted higher subsequent anxiety symptoms only in adolescents with low to moderate levels of extraversion. No sex moderation was found. While social media use (active or problematic) predicted later anxiety symptoms (but not depression), the reverse was not the case. However, highly extraverted individuals seem to be less vulnerable to potential negative effects of social media use.

Comparison of different approaches to manage multi-site magnetic resonance spectroscopy clinical data analysis.

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.

Longitudinal associations between mother-child attachment security in toddlerhood and white matter microstructure in late childhood: a preliminary investigation.

Early childhood experiences are considered to influence the strength and effectiveness of neural connections and thus the development of brain connectivity. As one of the most pervasive and potent early relational experiences, parent-child attachment is a prime candidate to account for experience-driven differences in brain development. Yet, knowledge of the effects of parent-child attachment on brain structure in typically developing children is scarce and largely limited to grey matter, whereas caregiving influences on white matter (i.e. neural connections) have seldom been explored. This study examined whether normative variation in mother-child attachment security predicts white matter microstructure in late childhood and explored associations with cognitive-inhibition. Mother-child attachment security was assessed using home observations when children (N = 32, 20 girls) were 15 and 26 months old. White matter microstructure was assessed using diffusion magnetic resonance imaging when children were 10 years old. Child cognitive-inhibition was tested when children were 11 years old. Results revealed a negative association between mother-toddler attachment security and child white matter microstructure organization, which in turn related to better child cognitive-inhibition. While preliminary given the sample size, these findings add to the growing literature that suggests that rich and positive experiences are likely to decelerate brain development.

Brain metabolites measured with magnetic resonance spectroscopy in pediatric concussion and orthopedic injury: An Advancing Concussion Assessment in Pediatrics (A-CAP) study.

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.