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Background and Objectives: Despite a well-documented association between childhood traumatic brain injury and elevated risk for internalizing and externalizing behavior problems, the mechanisms through which family functioning contributes to individual variation in these behavioral outcomes remains poorly understood. This prospective cohort study aimed to assess the respective contribution of family functioning and child emotion regulation (ER) to post-injury behavior problems at 1-year follow-up, with a specific focus on evaluating the role of ER problems in mediating the effects of familial affective responsiveness and communication on child behavioral outcomes., Method: The study included 129 participants, comprising 86 children with medically confirmed mild-to-severe TBI, identified from consecutive hospital admissions, and 43 typically developing (TD) control children, of similar age and sex. Participants ranged in age from 6 to 15 years (mean age = 11.2 years). Parents completed validated assessments of post-acute family functioning and child emotion regulation problems at 6 months post-injury, as well as measures of child behavior problems at 1-year post-injury., Results: Although group differences in internalizing behaviors did not reach statistical significance, the TBI group exhibited significantly higher overall externalizing symptoms and was significantly more likely to display clinically elevated symptoms than TD controls at 1-year post-injury. Compared to TD controls, the TBI group displayed significantly greater ER problems, which mediated the effects of lower familial affective responsiveness and communication on child behavior problems 1-year-post-injury., Conclusions: Evidence for these robust, prospective associations suggests that child emotion regulation problems play a key role in mediating the effect of post-acute family functioning on long-term behavior problems in children with TBI. Early assessment and screening for relevant risk factors may help identify those children and families who could benefit from therapeutic interventions designed to address emotional dysregulation and mitigate risk for post-injury behavioral problems. Importantly, these findings underscore the value of adopting family-centred care approaches in rehabilitation, where involving families in therapeutic processes and addressing family dynamics may enhance child emotion regulation and improve long-term behavioral outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vicki Anderson reports financial support was provided by Victoria Neurotrauma Initiative. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

This prospective cohort study aimed to evaluate the potential role of injury, socio-demographic and individual psychological factors in predicting long-term fatigue outcomes in young adult survivors of childhood TBI at 16-years post-injury. The study included 51 young adults diagnosed with childhood TBI from 2-12 years of age. Twenty age-and-sex-matched controls were included for comparison. Findings showed that almost one-in-four TBI participants (24%) endorsed clinically elevated fatigue at 16-years post-injury. Despite the relatively large proportion of TBI participants endorsing clinically significant fatigue, group comparisons revealed that the TBI and control groups did not significantly differ on fatigue symptom severity or rates of clinically elevated fatigue. For the TBI group, post-injury fatigue was significantly associated with socio-demographic and psychological factors, including lower educational level, higher depression symptom severity, and more frequent substance use. Higher fatigue was also associated with lower self-reported quality of life (QoL) in the physical, psychological, and environmental domains, even after controlling for depressive symptom severity, socio-demographic, and injury-related factors. Overall, findings show that a substantial proportion of young adults with a history of childhood TBI experience clinically elevated fatigue at 16-years post-injury. Identification and treatment of modifiable risk-factors (e.g. depression symptoms, substance use) has potential to reduce fatigue.

Despite growing research linking childhood traumatic brain injury (TBI) with reduced wellbeing, self-esteem, and psycho-social health, very few studies have examined self-esteem and its correlates in young adult survivors of childhood TBI. This very-long-term follow-up study evaluated self-esteem in 29 young adults with a history of childhood TBI (M time since injury = 13.84 years; SD = 0.74), and 10 typically developing controls (TDCs). All participants were originally recruited into a larger, longitudinal case-control study between 2007 and 2010. In the current follow-up study, both groups completed well-validated measures of self-esteem and mental health in young adulthood. Although group means for self-esteem did not significantly differ between TBI and TDC groups, a higher proportion of TBI participants rated their self-esteem in the clinical range (TBI grou p  = 17%; TDC grou p  = 0%). While self-esteem was not significantly associated with injury or pre-injury child or family characteristics, lower self-esteem was significantly correlated with greater concurrent feelings of loneliness ( p  = 0.007) and higher concurrent mood symptoms ( p  < 0.001).Our results suggest that social isolation and low mood may represent meaningful targets for psycho-social interventions to address poor self-worth in young adults with a history of childhood TBI.

Background: While theoretical models have established the bidirectional relationship between health and wellbeing of parents and children with chronic health conditions (CHCs), previous work has predominantly emphasised the impact of parent functioning on child outcomes. This study examines how quality of life (QoL) domains in children with CHCs are associated with unmet supportive care needs (SCN) of their parents and explores whether these associations vary by health condition., Method: Parents of children with congenital heart disease (CHD), type 1 diabetes (T1D) and cancer diagnosed before the age of 12 years and receiving treatment within the last 5 years were eligible. Parents recruited through charity organisations and social media platforms completed a secure, online survey via Qualtrics. The PedsQL examined child QoL across four dimensions: physical, emotional, social and school functioning. A 34-item survey assessed parents' unmet SCN in the previous month across six need domains (e.g., care and informational). Linear regressions examined associations between child QoL and unmet SCN domains and moderation analyses determined whether associations varied as a function of CHC., Results: The study included 186 parents (age range 25-56 years) of children diagnosed with various CHCs (52% CHD; 27% T1D, 21% cancer). The child's emotional functioning was inversely related to all unmet SCN domains, social functioning was inversely related to three domains (physical and social; support; financial), school functioning was inversely related to two domains (physical and social; care), and child's physical functioning was not associated with any SCN domains. Only the association between child school functioning and unmet care needs was significantly moderated by CHC type (p < 0.05)., Conclusion: Poorer emotional functioning in children with a CHC is a key factor in determining parents unmet SCN. Larger studies are required to replicate these findings and inform design of interventions addressing QoL and unmet SCN in families of children with common CHCs., (© 2024 The Author(s). Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Background: Depression, anxiety, and stress are persistent and co-occurring symptoms in survivors of childhood traumatic brain injury (TBI), and often impact on health-related quality of life (HRQoL). This paper explored emotional distress symptom clusters and associated factors in young adults with childhood TBI., Methods: We included 54 young adults who sustained mild ( n  = 14), moderate ( n  = 27), and severe ( n  = 13) childhood TBI, at 20 years post-injury. The Depression Anxiety Stress Scale was administered. Cluster group membership was identified using two-step clustering and hierarchical clustering methods, and associated factors were assessed with multiple regression models., Results: Two symptom cluster groups were identified, including a No Distress (n =  66%) and an Elevated Distress (n =  33%) group , with the latter showing significantly higher symptoms of depression, anxiety, and stress (all p  < .001). Elevated Distress group membership was linked to tobacco use and poor sleep quality, while poor HRQoL was associated with younger age at injury and Elevated Distress group membership., Conclusions: Using cluster methodology, we showed that one-third of young adults with childhood TBI had elevated emotional distress symptoms. This underscores the complex emotional profile of this subgroup and the need for assessment, analysis, and treatment methods that target a range of symptoms rather than relying on single-diagnostic protocols., Abbreviations: ANOVA: Analysis of Variance; CT: Computed Tomography; DASS: Depression Anxiety Stress Scale; GCS: Glasgow Coma Scale; HREC: Human Research Ethics Committee; HRQoL: Health-Related Quality of Life; IBM: International Business Machines Corporation; MRI: Magnetic Resonance Imaging; PTA: Post-Traumatic Amnesia; QoL: Quality of Life; QOLIBRI: Quality of Life after Brain Injury Scale; REDCap: Research Electronic Data Capture; SES: Socioeconomic Status; SPSS: Statistical Package for the Social Sciences; TBI: Traumatic Brain Injury.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia ( p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores ( p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Objective: To assess parent psychological distress in families of children with common chronic health conditions (CHC) and to explore relationships between parent psychological distress, unmet supportive care needs and children's quality of life (QoL)., Method: Cross-sectional study involving parents of children diagnosed with a common CHC between 0 and 12 years of age and who had received treatment within the last 5 years. Eligible parents completed an online survey, that included the Depression Anxiety Stress Scale (DASS-21) assessing distress in parents and a 34-item assessment of unmet supportive care needs across 6 domains. Parents completed ratings of their child's current functioning (QoL) using the 23-item PedsQL. Multivariable regression models examined the relative association between unmet needs, children's QoL and parents' depression, anxiety, and stress., Results: The sample consisted of 194 parents of children with congenital heart disease (n=97; 50%), diabetes (n=50; 26%), cancer (n=39; 20%), and asthma (n=8; 4%). A significant proportion of parents had moderate-severe symptoms of depression (26%), anxiety (38%), and stress (40%). Of the PedsQL scales, the poorest outcomes were found for emotional and school functioning. Multivariable analyses showed that both higher unmet needs and poorer child emotional functioning were associated with parent depression, anxiety, and stress symptoms., Conclusion: Evidence linking parent distress symptoms to higher unmet needs and poorer child emotional functioning suggests these factors may be targets for interventions to alleviate parent distress. Longitudinal research using larger samples is required to replicate findings, and clarify the magnitude and direction of associations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology.)

Despite evidence of a link between childhood TBI and heightened risk for depressive symptoms, very few studies have examined early risk factors that predict the presence and severity of post-injury depression beyond 1-year post injury. This longitudinal prospective study examined the effect of mild-severe childhood TBI on depressive symptom severity at 2-years post-injury. It also evaluated the potential role of sub-acute brain morphometry and executive function (EF) in prospectively predicting these long-term outcomes. The study involved 81 children and adolescents with TBI, and 40 age-and-sex matched typically developing (TD) controls. Participants underwent high-resolution structural magnetic resonance imaging (MRI) sub-acutely at five weeks post-injury (M = 5.55; SD = 3.05 weeks) and EF assessments were completed at 6-months post-injury. Compared to TD controls, the TBI group had significantly higher overall internalizing symptoms and were significantly more likely to exhibit clinically significant depressive symptoms at 2-year follow-up. The TBI group also displayed significantly lower EF and altered sub-acute brain morphometry in EF-related brain networks, including the default-mode network (DMN), salience network (SN) and central executive network (CEN). Mediation analyses revealed significant indirect effects of CEN morphometry on depression symptom severity, such that lower EF mediated the prospective association between altered CEN morphometry and higher depression symptoms in the TBI group. Parallel mediation analyses including grey matter morphometry of a non-EF brain network (i.e., the mentalising network) were not statistically significant, suggesting some model specificity. The findings indicate that screening for early neurostructural and neurocognitive risk factors may help identify children at elevated risk of depressive symptoms following TBI. For instance, children at greatest risk of post-injury depression symptoms could be identified based in part on neuroimaging of networks implicated in EF and post-acute assessments of executive function, which could support more effective allocation of limited intervention resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to identify similarities and differences in the unmet supportive care needs (USCN) of families of children with major chronic health conditions (CHCs) using a universal need assessment tool., Methods: A cross-sectional online survey involving parents of children with congenital heart disease (CHD), type 1 diabetes mellitus (T1D), cancer, and asthma diagnosed within the last 5 years recruited via social media and support organizations. Thirty-four items assessing the USCN across six domains (care needs, physical and social needs, informational needs, support needs, financial needs, child-related emotional needs) were responded to on a 4-point Likert scale [no need (1) to high need (4)]. Descriptive statistics identified the level of need, and linear regressions identified factors associated with higher need domain scores. Due to small numbers, the asthma group was excluded from comparisons across CHCs., Results: One hundred and ninety-four parents completed the survey (CHD: n = 97, T1D: n = 50, cancer: n = 39, and asthma: n = 8). Parents of children with cancer were most likely to report at least one USCN (92%), followed by parents of children with T1D (62%). The five most commonly reported USCN across CHCs were drawn from four domains: child-related emotional, support, care, and financial. Three need items were included in the top five needs for all conditions. A higher USCN was associated with a greater frequency of hospital visits and the absence of parental support., Conclusions: Using a universal need assessment tool, this is one of the first studies to characterize USCN in families of children diagnosed with common CHCs. While proportions endorsing different needs varied across conditions, the most endorsed needs were similar across the illness groups. This suggests that support programs or services could be shared across different CHCs. Video Abstract., (© 2023. The Author(s).)

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning., Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function., Design, Setting, and Participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or healthy controls (some with orthopedic injury) were recruited from trauma centers, clinics, and institutional trauma registries, some of which were followed longitudinally over a period of 0.7 to 1.9 years. Healthy controls were recruited from the surrounding community. Data analysis occurred from October to December 2022., Exposure: Accidental mild complicated-severe TBI (msTBI) for those in the TBI group. Some controls received a diagnosis of orthopedic injury., Main Outcomes and Measures: Volume of 18 cerebellar lobules and vermal regions were estimated from 3-dimensional T1-weighted magnetic resonance imaging (MRI) scans. White matter organization in 28 regions of interest was assessed with diffusion tensor MRI. Executive function was measured by parent-reported scores from the Behavior Rating Inventory of Executive Functioning., Results: A total of 598 children and adolescents (mean [SD] age, 14.05 [3.06] years; range, 5.45-19.70 years; 386 male participants [64.5%]; 212 female participants [35.5%]) were included in the study, with 314 participants in the msTBI group, and 284 participants in the non-TBI group (133 healthy individuals and 151 orthopedically injured individuals). Significantly smaller total cerebellum volume (d = -0.37; 95% CI, -0.52 to -0.22; P < .001) and subregional cerebellum volumes (eg, corpus medullare; d = -0.43; 95% CI, -0.58 to -0.28; P < .001) were observed in the msTBI group. These alterations were primarily seen in participants in the chronic phase (ie, >6 months postinjury) of injury (total cerebellar volume, d = -0.55; 95% CI, -0.75 to -0.35; P < .001). Smaller cerebellum volumes were associated with higher scores on the Behavior Rating Inventory of Executive Functioning Global Executive Composite score (β = -208.9 mm3; 95% CI, -319.0 to -98.0 mm3; P = .008) and Metacognition Index score (β = -202.5 mm3; 95% CI, -319.0 to -85.0 mm3; P = .02). In a subset of 185 participants with longitudinal data, younger msTBI participants exhibited cerebellum volume reductions (β = 0.0052 mm3; 95% CI, 0.0013 to 0.0090 mm3; P = .01), and older participants slower growth rates. Poorer white matter organization in the first months postinjury was associated with decreases in cerebellum volume over time (β=0.52 mm3; 95% CI, 0.19 to 0.84 mm3; P = .005)., Conclusions and Relevance: In this cohort study of pediatric msTBI, our results demonstrated robust cerebellar volume alterations associated with pediatric TBI, localized to the posterior lobe. Furthermore, longitudinal cerebellum changes were associated with baseline diffusion tensor MRI metrics, suggesting secondary cerebellar atrophy. These results provide further understanding of secondary injury mechanisms and may point to new opportunities for intervention.

Background and Aims: Unmet supportive care needs (SCN) refer to perceived gaps in the support parents want to manage caregiving activities for children with chronic health conditions (CHC) and the support received. This review aims to systematically identify the unmet SCN of families with children living with five common paediatric CHC and characterise the assessment tools used to measure SCN., Design: Systematic review methodology with narrative synthesis of data. Reporting followed the PRISMA statement guidelines., Method: Literature searches were conducted in electronic databases Medline complete, PsycINFO, CINHAL and EMBASE to retrieve relevant articles published between 1990 and July 2022. Eligible studies involved (i) children aged 0-18 years diagnosed with either of cancer, congenital heart disease (CHD), diabetes, asthma, renal disease and (ii) assessment of unmet SCN. Studies involving children with genetic or developmental conditions were excluded. The methodological quality of studies was assessed using JBI assessment tool., Results: Of 6223 articles screened, 34 papers were included (25 quantitative, 5 qualitative and 4 mixed design). Most papers explored unmet needs of families with cancer (n = 26). The remaining articles concerned CHD (n = 5), asthma (n = 2) and mixed CHC (n = 1, renal failure, and diabetes). Information (e.g. treatment, lifestyle, etc.) and health care (e.g. emotional support, practical services, etc.) were the most common unmet need domains across health conditions. A variety of methods and need assessments hampered comparisons between studies both across and within CHC., Conclusion: Irrespective of illness, addressing unmet informational or health care needs may help to optimise outcomes and care for children and families living with common CHC. There was considerable variation in reporting styles, study design and need assessments both within and across conditions., Relevance to Clinical Practice: Health care professionals must routinely evaluate the type, quality and quantity of psychoeducation and support that families of children with CHC want and receive. Providing nurses with more effective strategies to assess child and family needs across a broad range of domains may help to increase understanding of where further support for families is required., Patient or Public Contribution: There was no patient or public contribution to this study as it involved a systematic review of existing literature., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Pediatric traumatic brain injury (TBI) can impact psycho-social functioning, including friendships and experiences of loneliness; however, few studies have explored associations between these factors and self-esteem. To address this gap, the objective of this study was to document inter-relationships between friendship quality, peer-related loneliness, and self-esteem 12 months post-injury. The sample in this prospective, longitudinal observational study consisted of 135 children, including 92 children with TBI (57 mild, 35 moderate-severe TBI) and 43 typically developing control (TDC) children. Children rated their friendship quality, loneliness, and self-esteem. Parents completed questionnaires measuring socioeconomic status and children's pre-injury functioning. At 12-month follow-up, ratings of friendship quality (perceived support and satisfaction with friendships), peer-related loneliness, and self-esteem were comparable between TBI and TDC participants. In mediation models, poorer quality friendships were associated with greater peer-related loneliness, and greater peer-related loneliness was related to reduced athletic and social self-esteem, at 12 months post-TBI. Loneliness with peers mediated the effects of both friendship support and friendship satisfaction on children's social self-esteem. Our preliminary findings suggest that regular monitoring of social interactions post-TBI might facilitate early identification of children who are likely to benefit from interventions targeting peer-related loneliness, which in turn may lower risk for poorer self-esteem.

Background: Despite a well-established link between childhood traumatic brain injury (TBI) and elevated secondary attention-deficit/hyperactivity disorder (s-ADHD) symptomology, the neurostructural correlates of these symptoms are largely unknown. Based on the influential 'triple-network model' of ADHD, this prospective longitudinal investigation aimed to (i) assess the effect of childhood TBI on brain morphometry of higher-order cognitive networks proposed to play a key role in ADHD pathophysiology, including the default-mode network (DMN), salience network (SN) and central executive network (CEN); and (ii) assess the independent prognostic value of DMN, SN and CEN morphometry in predicting s-ADHD symptom severity after childhood TBI., Methods: The study sample comprised 155 participants, including 112 children with medically confirmed mild-severe TBI ascertained from consecutive hospital admissions, and 43 typically developing (TD) children matched for age, sex and socio-economic status. High-resolution structural brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 103 children with TBI and 34 TD children. Parents completed well-validated measures of ADHD symptom severity at 12-months post injury., Results: Relative to TD children and those with milder levels of TBI severity (mild, complicated mild, moderate), children with severe TBI showed altered brain morphometry within large-scale, higher-order cognitive networks, including significantly diminished grey matter volumes within the DMN, SN and CEN. When compared with the TD group, the TBI group showed significantly higher ADHD symptomatology and higher rates of clinically elevated symptoms. In multivariable models adjusted for other well-established risk factors, altered DMN morphometry independently predicted higher s-ADHD symptomatology at 12-months post-injury, whilst SN and CEN morphometry were not significant independent predictors., Conclusions: Our prospective study findings suggest that neurostructural alterations within higher-order cognitive circuitry may represent a prospective risk factor for s-ADHD symptomatology at 12-months post-injury in children with TBI. High-resolution structural brain MRI has potential to provide early prognostic biomarkers that may help early identification of high-risk children with TBI who are likely to benefit from early surveillance and preventive measures to optimise long-term neuropsychiatric outcomes.

Background: Psychosocial deficits, such as emotional, behavioral and social problems, reflect the most common and disabling consequences of pediatric traumatic brain injury (TBI). Their causes and recovery likely differ from physical and cognitive skills, due to disruption to developing brain networks and the influence of the child's environment. Despite increasing recognition of post-injury behavioral and social problems, there exists a paucity of research regarding the incidence of social impairment, and factors predicting risk and resilience in the social domain over time since injury., Methods: Using a prospective, longitudinal design, and a bio-psychosocial framework, we studied children with TBI ( n = 107) at baseline (pre-injury function), 6 months, 1 and 2-years post-injury. We assessed intellectual ability, attention/executive function, social cognition, social communication and socio-emotional function. Children underwent structural magnetic resonance imaging (MRI) at 2-8 weeks post-injury. Parents rated their child's socio-emotional function and their own mental health, family function and perceived burden., Results: We distinguished five social recovery profiles, characterized by a complex interplay between environment and pre- and post-TBI factors, with injury factors playing a lesser role. Resilience in social competence was linked to intact family and parent function, intact pre-injury adaptive abilities, post-TBI cognition and social participation. Vulnerability in the social domain was related to poor pre- and post-injury adaptive abilities, greater behavioral concerns, and poorer pre- and post-injury parent health and family function., Conclusions: We identified five distinct social recovery trajectories post-child-TBI, each characterized by a unique biopsychosocial profile, highlighting the importance of comprehensive social assessment and understanding of factors contributing to social impairment, to target resources and interventions to children at highest risk.

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences., Competing Interests: Competing Interest Statement: Dr. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Dr. Brodtmann serves on the editorial boards of Neurology and International Journal of Stroke. Dr. Diaz-Caneja has received honoraria from Exeltis and Angelinii. Dr. Giza: consultant for NBA, NFL, NHLPA, Los Angeles Lakers; Advisory Board: Highmark Interactive, Novartis, MLS, NBA, USSF; Medicolegal 1–2 cases annually. Dr. Soares: ALKERMES (Research Grant), ALLERGAN (Research Grant), ASOFARMA (Consultant), ATAI (Stock), BOEHRINGER Ingelheim (Consultant), COMPASS (Research Grant), JOHNSON & JOHNSON (Consultant), LIVANOVA (Consultant), PFIZER (Consultant), PULVINAR NEURO LLC (Consultant), RELMADA (Consultant), SANOFI (Consultant), SUNOVIAN (Consultant). Dr. Thompson received partial research support from Biogen, Inc., for research unrelated to this manuscript. Dr. Yatham has been on speaker or advisory boards for, or has received research grants from, Alkermes, Abbvie, Canadian Institutes of Health Research, Sumitomo Dainippon Pharma, GlaxoSmithKline, Intracellular Therapies, Merck, Sanofi, Sequiris, Servier, and Sunovion, over the past 3 years, all outside this work. The collection of this cohort was partially supported by an investigator-initiated research grant from Biogen (US). Biogen had no role in the analysis or writing of this manuscript. Eisai (JP) and Life Molecular Imaging for research unrelated to this manuscript. Dr. Wylie has received research support from the NJ Commission for brain injury research, from the Dept of Veterans’ Affairs, from Biogen, from Bristol, Myers, Squibb, from Genetech, and has served on advisory boards for the CDMRP and the VA. All of these activities are unrelated to this research. The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.

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.

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.)

We performed a systematic review and meta-analysis to identify, classify and evaluate the body of evidence on novel wearable and contactless devices that measure heart rate, respiratory rate and oxygen saturations in the clinical setting. We included any studies of hospital inpatients, including sleep study clinics. Eighty-four studies were included in the final review. There were 56 studies of wearable devices and 29 of contactless devices. One study assessed both types of device. A high risk of patient selection and rater bias was present in proportionally more studies assessing contactless devices compared with studies assessing wearable devices (p = 0.023 and p < 0.0001, respectively). There was high but equivalent likelihood of blinding bias between the two types of studies (p = 0.076). Wearable device studies were commercially available devices validated in acute clinical settings by clinical staff and had more real-time data analysis (p = 0.04). Contactless devices were more experimental, and data were analysed post-hoc. Pooled estimates of mean (95%CI) heart rate and respiratory rate bias in wearable devices were 1.25 (-0.31-2.82) beats.min -1 (pooled 95% limits of agreement -9.36-10.08) and 0.68 (0.05-1.32) breaths.min -1 (pooled 95% limits of agreement -5.65-6.85). The pooled estimate for mean (95%CI) heart rate and respiratory rate bias in contactless devices was 2.18 (3.31-7.66) beats.min -1 (pooled limits of agreement -6.71-10.88) and 0.30 (-0.26-0.87) breaths.min -1 (pooled 95% limits of agreement -3.94-4.29). Only two studies of wearable devices measured S p O 2 ; these reported mean measurement biases of 3.54% (limits of agreement -5.65-11.45%) and 2.9% (-7.4-1.7%). Heterogeneity was observed across studies, but absent when devices were grouped by measurement modality and reference standard. We conclude that, while studies of wearable devices were of slightly better quality than contactless devices, in general all studies of novel devices were of low quality, with small (< 100) patient datasets, typically not blinded and often using inappropriate statistical techniques. Both types of devices were statistically equivalent in accuracy and precision, but wearable devices demonstrated less measurement bias and more precision at extreme vital signs. The statistical variability in precision and accuracy between studies is partially explained by differences in reference standards., (© 2022 Association of Anaesthetists.)

This prospective, longitudinal case-control study examined global and domain-specific aspects of self-esteem 6-months following pediatric traumatic brain injury (TBI) and evaluated the contribution of injury-related factors and parent mental health to child self-esteem. Participants included 103 children with mild-severe TBI representing consecutive admissions to the emergency department of the Royal Children's Hospital, Melbourne, Australia. Forty-three age-and-sex matched typically developing controls were recruited for comparison. Information regarding injury characteristics including age at injury and clinical indicators of TBI severity were collected for participants at recruitment, with research magnetic resonance imaging conducted 2-8 weeks later. At 6 months post-injury, children rated their global and domain-specific self-esteem (Harter Self-Perception Profile for Children), and ratings of parent mental health were collected (General Health Questionnaire). Self-esteem for behavioural and academic domains was significantly poorer for children with TBI relative to TD children. In the TBI group, higher child-rated scores of global and domain-specific aspects of self-esteem were associated with more severe TBI, presence of frontal neuropathology, younger age at injury, and lower parental symptoms of anxiety/insomnia. Given the psychological status of parents represents a potentially modifiable risk factor, it may form the target of clinical interventions designed to bolster child self-esteem following pediatric TBI.

Recent evidence suggests social cognitive deficits may be among the most profound and disabling consequences of childhood traumatic brain injury (TBI); however, it is only over the last decade that this area has received increasing research attention. This study aims to systematically review all studies reporting on the effects of childhood TBI on social cognition. Meta-analytic techniques were employed to determine the magnitude of social cognitive deficits in childhood TBI. Literature searches were conducted in electronic databases (Medline/PubMed, Scopus, Cochrane, EMBASE, PsycINFO and CINAHL) to retrieve relevant articles on social cognitive outcomes of paediatric TBI published from 2007-2019. The systematic review identified fourteen eligible studies, which examined the effect of paediatric TBI on five dimensions of social cognition, including emotion recognition or perception, theory of Mind (ToM), pragmatic language, moral reasoning, and social problem solving. Of these studies, eleven articles were included in subsequent meta-analyses, which included 482 children with TBI. Meta-analysis using a random-effects model revealed non-significant differences between TBI and typically developing (TD) control groups on measures of emotion perception or recognition. In contrast, children and adolescents with TBI performed significantly worse than control groups on ToM and pragmatic language tasks, with small and medium effect sizes, respectively (Hedge's g = -0.46; -0.73). Meta-regression indicated that post-injury social cognitive deficits were not moderated by child age. While the effect of time since injury was not statistically significant, poorer social cognitive outcomes are documented soon after injury. Despite relatively intact basic social cognitive skills (i.e. emotion perception or recognition) children and adolescents with TBI are vulnerable to deficits in higher-order aspects of social cognition, including ToM and pragmatic language. These findings underscore the importance of further research, using well-validated, standardised outcome instruments, in larger paediatric TBI samples. Furthermore, longitudinal prospective studies are needed to evaluate the respective contribution of injury and non-injury factors to individual variation in outcome and recovery of social cognition after paediatric TBI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Importance: Social deficits are a common and disabling feature of many pediatric disorders; however, whether behavioral interventions are associated with benefits for children and adolescents with social deficits is poorly understood., Objective: To assess whether behavioral interventions in children and adolescents with neurodevelopmental or mental health disorders are associated with improvements in social function and social cognition, and whether patient, intervention, and methodological characteristics moderate the association., Data Sources: For this systematic review and meta-analysis, the PsycINFO, MEDLINE, and PubMed electronic databases were searched in December 2020 for randomized clinical trials published from database inception to December 1, 2020, including terms related to neurodevelopmental or mental health disorders, social behavior, randomized clinical trials, and children and adolescents. Data were analyzed in January 2021., Study Selection: Randomized clinical trials that enrolled participants aged 4 to 17 years with social deficits and examined the efficacy of a clinician-administered behavioral intervention targeting social functioning or social cognition were included. A total of 9314 records were identified, 78 full texts were assessed for eligibility, and 33 articles were included in the study; 31 of these reported social function outcomes and 12 reported social cognition outcomes., Data Extraction and Synthesis: Articles were reviewed using the Cochrane Risk of Bias Assessment for randomized clinical trials. Data were independently extracted and pooled using a weighted random-effects model., Main Outcomes and Measures: The main outcome was the association of behavioral intervention with social function and social cognition. Hedges g was used to measure the standardized mean difference between intervention and control groups. Standardized effect sizes were calculated for the intervention group vs the comparison group for each trial., Results: A total of 31 trials including 2131 participants (1711 [80%] male; 420 [20%] female; mean [SD] age, 10.8 [2.2] years) with neurodevelopmental or mental health disorders (autism spectrum disorder [ASD] [n = 23], attention-deficit/hyperactivity disorder [n = 4], other conditions associated with social deficits [n = 4]) were analyzed to examine differences in social function between the intervention and control groups. Significantly greater gains in social function were found among participants who received an intervention than among the control groups (Hedges g, 0.61; 95% CI, 0.40-0.83; P < .001). The type of control condition (wait list vs active control vs treatment as usual) was a significant moderator of effect size (Q2, 7.11; P = .03). Twelve studies including 487 individuals with ASD (48 [10%] female; 439 [90%] male; mean [SD] age, 10.4 [1.7] years) were analyzed to examine differences in social cognition between intervention and control groups. The overall mean weighted effect was significant (Hedges g, 0.67; 95% CI, 0.39-0.96; P < .001), indicating the treatment groups had better performance on social cognitive tasks., Conclusions and Relevance: In this systematic review and meta-analysis, significantly greater gains in social function and social cognition were reported among children and adolescents who received behavioral interventions for social deficits compared with participants receiving the control conditions. These findings suggest that children and adolescents with social deficits might benefit from social skills training regardless of their specific neurodevelopmental or mental health diagnosis.

Background: Despite increasing evidence of a link between early life brain injury and anti-social behavior, very few studies have assessed factors that explain this association in children with traumatic brain injury (TBI). One hypothesis suggests that childhood TBI elevates risk for anti-social behavior via disruption to anatomically distributed neural networks implicated in executive functioning (EF). In this longitudinal prospective study, we employed high-resolution structural neuroimaging to (a) evaluate the impact of childhood TBI on regional morphometry of the central executive network (CEN) and (b) evaluate the prediction that lower EF mediates the prospective relationship between structural differences within the CEN and postinjury anti-social behaviors., Methods: This study involved 155 children, including 112 consecutively recruited, hospital-confirmed cases of mild-severe TBI and 43 typically developing control (TDC) children. T1-weighted brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 137 children [TBI: n = 103; TDC: n = 34]. All participants were evaluated using direct assessment of EF 6 months postinjury, and parents provided ratings of anti-social behavior 12 months postinjury., Results: Severe TBI was associated with postinjury volumetric differences within the CEN and its putative hub regions. When compared with TD controls, the TBI group had significantly worse EF, which was associated with more frequent anti-social behaviors and abnormal CEN morphometry. Mediation analysis indicated that reduced EF mediated the prospective association between postinjury volumetric differences within the CEN and more frequent anti-social behavior., Conclusions: Our longitudinal prospective findings suggest that detection of neurostructural abnormalities within the CEN may aid in the early identification of children at elevated risk for postinjury executive dysfunction, which may in turn contribute to chronic anti-social behaviors after early life brain injury. Findings underscore the potential value of early surveillance and preventive measures for children presenting with neurostructural and/or neurocognitive risk factors., (© 2021 Association for Child and Adolescent Mental Health.)

Objective: Our study addressed aims (1) to test the hypothesis that moderate-severe traumatic brain injury (TBI) in pediatric patients is associated with widespread white matter (WM) disruption, (2) to test the hypothesis that age and sex affect WM organization after injury, and (3) to examine associations between WM organization and neurobehavioral outcomes., Methods: Data from 10 previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Pediatric Moderate/Severe TBI (msTBI) working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline., Results: Five hundred seven children and adolescents (244 with complicated msTBI and 263 controls) were included. Patients were clustered into 3 postinjury intervals: acute/subacute, <2 months; postacute, 2 to 6 months; and chronic, ≥6 months. Outcomes were dMRI metrics and postinjury behavioral problems as indexed by the Child Behavior Checklist. Our analyses revealed altered WM diffusion metrics across multiple tracts and all postinjury intervals (effect sizes range d = -0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time after injury. We observed a sex-by-group interaction: female patients with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (β = 0.043), which coincided with more parent-reported behavioral problems (β = -0.0027)., Conclusions: WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically meaningful patient subtypes., (© 2021 American Academy of Neurology.)

Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS., Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities., Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems., Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction.

Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population, and specific developmental issues require a unique context since findings from adult research do not necessarily directly translate to children. Findings in pediatric cohorts tend to lag behind those in adult samples. This may be due, in part, both to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate/Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis of neuroimaging data. In this paper, we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. With the paucity of research studies examining neuroimaging biomarkers in pediatric patients with TBI and the challenges of recruiting large numbers of participants, collaborating to improve statistical power and to address technical challenges like lesions will significantly advance the field. We conclude with recommendations for future research in this field of study.

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.

Neuroimaging is being increasingly applied to the study of paediatric mild traumatic brain injury (mTBI) to uncover the neurobiological correlates of delayed recovery post-injury. The aims of this systematic review were to: (i) evaluate the neuroimaging research investigating neuropathology post-mTBI in children and adolescents from 0-18 years, (ii) assess the relationship between advanced neuroimaging abnormalities and PCS in children, (iii) assess the quality of the evidence by evaluating study methodology and reporting against best practice guidelines, and (iv) provide directions for future research. A literature search of MEDLINE, PsycINFO, EMBASE, and PubMed was conducted. Abstracts and titles were screened, followed by full review of remaining articles where specific eligibility criteria were applied. This systematic review identified 58 imaging studies which met criteria. Based on several factors including methodological heterogeneity and relatively small sample sizes, the literature currently provides insufficient evidence to draw meaningful conclusions about the relationship between MRI findings and clinical outcomes. Future research is needed which incorporates prospective, longitudinal designs, minimises potential confounds and utilises multimodal imaging techniques., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: This study assessed the consequences of childhood traumatic brain injury (TBI) on sleep, fatigue, depression, and quality of life (QoL) outcomes and explored the relationships between these variables at 20 years following childhood TBI., Participants: We followed up 54 young adults with mild, moderate, and severe TBI, and 13 typically developing control (TDC) participants, recruited at the time of TBI., Methods: Sleep was assessed with the Pittsburgh Sleep Quality Index and actigraphy., Results: At 20 years postinjury, results showed no significant difference between whole TBI group and TDC participants on subjective sleep quality; however, the moderate TBI group reported significantly poorer subjective sleep quality compared to those with severe TBI. Poorer subjective sleep was associated with increased symptoms of fatigue, depression, and poorer perceptions of General Health in the TBI group. Actigraphic sleep efficiency, fatigue, depression, and QoL outcomes were not significantly different between TBI and TDC or among TBI severity groups., Conclusions: These preliminary findings underscore associations between subjective sleep disturbance, fatigue, depression, and QoL in this TBI sample, and mostly comparable outcomes in sleep, fatigue, depression, and QoL between the TBI and TDC groups. Further research is required to clarify these findings.

Traumatic brain injury (TBI) during critical periods of early-life brain development can affect the normal formation of brain networks responsible for a range of complex social behaviors. Because of the protracted nature of brain and behavioral development, deficits in cognitive and socioaffective behaviors may not become evident until late adolescence and early adulthood, when such skills are expected to reach maturity. In addition, multiple pre- and post-injury factors can interact with the effects of early brain insult to influence long-term outcomes. In recent years, with advancements in magnetic-resonance-based neuroimaging techniques and analysis, studies of the pediatric population have revealed a link between neurobehavioral deficits, such as social dysfunction, with white matter damage. In this review, in which we focus on contributions from Australian researchers to the field, we have highlighted pioneering longitudinal studies in pediatric TBI, in relation to social deficits specifically. We also discuss the use of advanced neuroimaging and novel behavioral assays in animal models of TBI in the immature brain. Together, this research aims to understand the relationship between injury consequences and ongoing brain development after pediatric TBI, which promises to improve prediction of the behavioral deficits that emerge in the years subsequent to early-life injury.