Publications by authors named "Vicki Anderson"

418 Publications

Characteristics of concussion based on patient age and sex: a multicenter prospective observational study.

J Neurosurg Pediatr 2021 Oct 1:1-10. Epub 2021 Oct 1.

2Clinical Sciences, Murdoch Children's Research Institute, Melbourne.

Objective: Children with concussion frequently present to emergency departments (EDs). There is limited understanding of the differences in signs, symptoms, and epidemiology of concussion based on patient age. Here, the authors set out to assess the association between age and acute concussion presentations.

Methods: The authors conducted a multicenter prospective observational study of head injuries at 10 EDs in Australia and New Zealand. They identified children aged 5 to < 18 years, presenting with a Glasgow Coma Scale score of 13-15, presenting < 24 hours postinjury, with no abnormalities on CT if performed, and one or more signs or symptoms of concussion. They extracted demographic, injury-related, and signs and symptoms information and stratified it by age group (5-8, 9-12, 13 to < 18 years).

Results: Of 8857 children aged 5 to < 18 years, 4709 patients met the defined concussion criteria (5-8 years, n = 1546; 9-12 years, n = 1617; 13 to < 18 years, n = 1546). The mean age of the cohort was 10.9 years, and approximately 70% of the patients were male. Sport-related concussion accounted for 43.7% of concussions overall, increasing from 19.1% to 48.9% to 63.0% in the 5-8, 9-12, and 13 to < 18 years age groups. The most common acute symptoms postinjury were headache (64.6%), disorientation (36.2%), amnesia (30.0%), and vomiting (27.2%). Vomiting decreased with increasing age and was observed in 41.7% of the 5-8 years group, 24.7% of the 9-12 years group, and 15.4% of the 13 to < 18 years group, whereas reported loss of consciousness (LOC) increased with increasing age, occurring in 9.6% in the 5-8 years group, 21.0% in the 9-12 years group, 36.7% in the 13 to < 18 years group, and 22.4% in the entire study cohort. Headache, amnesia, and disorientation followed the latter trajectory. Symptom profiles were broadly similar between males and females.

Conclusions: Concussions presenting to EDs were more sports-related as age increased. Signs and symptoms differed markedly across age groups, with vomiting decreasing and headache, LOC, amnesia, and disorientation increasing with increasing age.
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http://dx.doi.org/10.3171/2021.6.PEDS20953DOI Listing
October 2021

The mediating role of ADHD symptoms between executive function and social skills in children with neurofibromatosis type 1.

Child Neuropsychol 2021 Sep 30:1-19. Epub 2021 Sep 30.

Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Australia.

Children with neurofibromatosis type 1 (NF1) often experience executive dysfunction, attention deficit/hyperactivity disorder (ADHD) symptoms and poor social skills, however, the nature of the relationships between these domains in children with NF1 is unclear. This study investigated these relationships using primary caregiver ratings of executive functions, ADHD symptoms and social skills in children with NF1. Participants were 136 children with NF1 and 93 typically developing (TD) controls aged 3-15 years recruited from 3 multidisciplinary neurofibromatosis clinics in Melbourne and Sydney, Australia, and Washington DC, USA. Mediation analysis was performed on primary outcome variables: parent ratings of executive functions (Behavior Rating Inventory of Executive Function, Metacognition Index), ADHD symptoms (Conners-3/Conners ADHD Diagnostic and Statistical Manual for Mental Disorders Scales) and social skills (Social Skills Improvement System-Rating Scale), adjusting for potential confounders (full scale IQ, sex, and social risk). Results revealed significantly poorer executive functions, elevated ADHD symptoms and reduced social skills in children with NF1 compared to controls. Poorer executive functions significantly predicted elevated ADHD symptoms and poorer social skills. Elevated ADHD symptoms significantly mediated the relationship between executive functions and social skills problems although did not fully account for social dysfunction. This study provides evidence for the importance of targeting ADHD symptoms as part of future interventions aimed at promoting prosocial behaviors in children with NF1.
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http://dx.doi.org/10.1080/09297049.2021.1976129DOI Listing
September 2021

Structural-covariance networks identify topology-based cortical-thickness changes in children with persistent executive function impairments after traumatic brain injury.

Neuroimage 2021 Sep 23;244:118612. Epub 2021 Sep 23.

College of Health and Life Sciences and Aston Institute of Health and Neurodevelopment, Aston University, Birmingham B4 7ET, UK; Brain and Mind Research, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; School of Psychology, Faculty of Health, Melbourne Burwood Campus, Deakin University, Geelong, Victoria, Australia.

Paediatric traumatic brain injury (pTBI) results in inconsistent changes to regional morphometry of the brain across studies. Structural-covariance networks represent the degree to which the morphology (typically cortical-thickness) of cortical-regions co-varies with other regions, driven by both biological and developmental factors. Understanding how heterogeneous regional changes may influence wider cortical network organization may more appropriately capture prognostic information in terms of long term outcome following a pTBI. The current study aimed to investigate the relationships between cortical organisation as measured by structural-covariance, and long-term cognitive impairment following pTBI. T1-weighted magnetic resonance imaging (MRI) from n = 83 pTBI patients and 33 typically developing controls underwent 3D-tissue segmentation using Freesurfer to estimate cortical-thickness across 68 cortical ROIs. Structural-covariance between regions was estimated using Pearson's correlations between cortical-thickness measures across 68 regions-of-interest (ROIs), generating a group-level 68 × 68 adjacency matrix for patients and controls. We grouped a subset of patients who underwent executive function testing at 2-years post-injury using a neuropsychological impairment (NPI) rule, defining impaired- and non-impaired subgroups. Despite finding no significant reductions in regional cortical-thickness between the control and pTBI groups, we found specific reductions in graph-level strength of the structural covariance graph only between controls and the pTBI group with executive function (EF) impairment. Node-level differences in strength for this group were primarily found in frontal regions. We also investigated whether the top n nodes in terms of effect-size of cortical-thickness reductions were nodes that had significantly greater strength in the typically developing brain than n randomly selected regions. We found that acute cortical-thickness reductions post-pTBI are loaded onto regions typically high in structural covariance. This association was found in those patients with persistent EF impairment at 2-years post-injury, but not in those for whom these abilities were spared. This study posits that the topography of post-injury cortical-thickness reductions in regions that are central to the typical structural-covariance topology of the brain, can explain which patients have poor EF at follow-up.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118612DOI Listing
September 2021

Engaging children and adolescents with acquired brain injury and their families in goal setting: The family perspective.

Neuropsychol Rehabil 2021 Sep 19:1-23. Epub 2021 Sep 19.

Department of Neurodisability and Rehabilitation, Murdoch Children's Research Institute, Melbourne, Australia.

This study explored the experiences of goal setting in paediatric rehabilitation from the perspectives of children and adolescents with acquired brain injury (ABI) and their parents in paediatric rehabilitation. Using a qualitative research design, 15 semi-structured interviews were conducted with 13 parents and 8 young people with ABI aged between 9 and 18 years who were engaged in outpatient rehabilitation. Interview transcripts were analysed using constructivist grounded theory methods. Two main themes and several sub-themes emerged: Experiences of goal setting: and Working as a team: and These themes reflect parent's and young people's experience of goal setting during paediatric rehabilitation for ABI and suggest clinicians play an important role in educating young people and their families about goal setting in the outpatient rehabilitation context. Young people and their parents also perceive the focus of outpatient rehabilitation as working collaboratively with clinicians to gain knowledge to manage the consequences of ABI. Our findings emphasize the importance of the therapeutic consumer-clinician relationship and the need to actively engage young people in goal setting.
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http://dx.doi.org/10.1080/09602011.2021.1977154DOI Listing
September 2021

Large-scale functional network dynamics in human callosal agenesis: Increased subcortical involvement and preserved laterality.

Neuroimage 2021 Nov 27;243:118471. Epub 2021 Aug 27.

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Switzerland; Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.

In the human brain, the corpus callosum is the major white-matter commissural tract enabling the transmission of sensory-motor, and higher level cognitive information between homotopic regions of the two cerebral hemispheres. Despite developmental absence (i.e., agenesis) of the corpus callosum (AgCC), functional connectivity is preserved, including interhemispheric connectivity. Subcortical structures have been hypothesised to provide alternative pathways to enable this preservation. To test this hypothesis, we used functional Magnetic Resonance Imaging (fMRI) recordings in children with AgCC and typically developing children, and a time-resolved approach to retrieve temporal characteristics of whole-brain functional networks. We observed an increased engagement of the cerebellum and amygdala/hippocampus networks in children with AgCC compared to typically developing children. There was little evidence that laterality of activation networks was affected in AgCC. Our findings support the hypothesis that subcortical structures play an essential role in the functional reconfiguration of the brain in the absence of a corpus callosum.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118471DOI Listing
November 2021

Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.

Stroke 2021 Oct 18;52(10):3296-3304. Epub 2021 Aug 18.

Neuroscience Research (J.Y.-M.Y., M.K., M.T.M.), Murdoch Children's Research Institute, Parkville, Australia.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032822DOI Listing
October 2021

Accuracy of Components of the SCAT5 and ChildSCAT5 to Identify Children with Concussion.

Int J Sports Med 2021 Aug 16. Epub 2021 Aug 16.

Department of Clinical Sciences, Murdoch Childrens Research Institute, Parkville, Australia.

The Sport Concussion Assessment Tool 5 Edition (SCAT5) is a standardized measure of concussion. In this prospective observational study, the ability of the SCAT5 and ChildSCAT5 to differentiate between children with and without a concussion was examined. Concussed children (n=91) and controls (n=106) were recruited from an emergency department in three equal-sized age bands (5-8/9-12/13-16 years). Analysis of covariance models (adjusting for participant age) were used to analyze group differences on components of the SCAT5. On the SCAT5 and ChildSCAT5, respectively, youth with concussion reported a greater number (=1.47; 0.52 and severity (1.27; 0.72) of symptoms than controls (all <0.001). ChildSCAT5 parent-rated number (=0.98) an severity (=1.04) of symptoms were greater for the concussion group (all <0.001). Acceptable levels of between-group discrimination were identified for SCAT5 symptom number (AUC=0.86) and severity (AUC=0.84) and ChildSCAT5 parent-rated symptom number (AUC=0.76) and severity (AUC=0.78). Our findings support the utility of the SCAT5 and ChildSCAT5 to accurately distinguish between children with and without a concussion.
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http://dx.doi.org/10.1055/a-1533-1700DOI Listing
August 2021

Post-concussive Signs and Symptoms in Preschool Children: A Systematic Review.

Neuropsychol Rev 2021 Aug 14. Epub 2021 Aug 14.

Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia.

Mild traumatic brain injury (mTBI) is common in children aged < 5 years, however, less is known about their experience of post-concussive signs and symptoms. This systematic review aims to identify post-concussive signs and symptoms experienced by preschool children up to 12 months post-injury, and to review the methods used to report this data. Relevant findings, including rates, progression, and possible predictors of post-concussive signs and symptoms were also identified. Databases (Ovid MEDLINE, EMBASE, PsycInfo, PubMed, Scopus) and reference lists were searched for relevant articles, which were screened based on specified criteria. Eleven articles met the inclusion criteria, being original studies published in English and presenting data on post-concussive signs and symptoms specific to preschool children with mTBI. Most reviewed studies investigated acute presentations of mTBI, and identified that preschool children demonstrate post-concussive symptoms (PCS) similar to other age groups. Post-traumatic amnesia duration of approximately one day was reported in preschool children following mTBI, as were changes in mood and behavior during the recovery period. Parents were the main informants, with data obtained through either interview or questionnaire. Review findings highlight the lack of empirical data regarding the presentation and progression of PCS in preschoolers following mTBI and evidence on how to best manage this group during recovery.
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http://dx.doi.org/10.1007/s11065-021-09518-zDOI Listing
August 2021

Inter-individual performance differences in the stop-signal task are associated with fibre-specific microstructure of the fronto-basal-ganglia circuit in healthy children.

Cortex 2021 09 26;142:283-295. Epub 2021 Jun 26.

Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia. Electronic address:

Previous Diffusion Tensor Imaging (DTI) studies in children suggest that developmental improvements in inhibitory control is largely mediated by the degree of white matter organisation within a right-lateralised network of fronto-basal-ganglia regions. Recent advances in diffusion imaging analysis now permit greater biological specificity, both in identifying specific fibre populations within a voxel, as well as in the underlying microstructural properties of that white matter. In the present work, employing a novel fixel-based analysis (FBA) framework, we aimed to comprehensively investigate microstructure within the fronto-basal-ganglia circuit in childhood, and its contribution to inhibition performance. Diffusion MRI data were obtained from 43 healthy children and adolescents aged 9-11 years (10.42 ± .41 years, 18 females). Response inhibition for each participant was assessed using the Stop-signal Task (SST) and quantified as a Stop-Signal Reaction Time (SSRT). All steps relevant to FBA were implemented in MRtrix3Tissue, a fork of the MRtrix3 software library. The fronto-basal-ganglia circuit were delineated using probabilistic tractography to identify the tracts connecting the subthalamic nucleus, pre-supplementary motor area and the inferior frontal gyrus. Connectivity-based fixel enhancement (CFE) was then used to assess the association between fibre density (FD) and fibre cross-section (FC) with inhibitory ability. Significant negative associations were identified for FD in both the right and left fronto-basal-ganglia circuit whereby greater FD was associated with better inhibition performance (e.g., reduced SSRTs). This effect was specifically localised to clusters of fixels within white matter proximal to the right subthalamic nucleus. We did not report any meaningful associations between SSRT and FC. Whilst findings are broadly consistent with prior DTI evidence, current results suggest that SSRT is predominantly facilitated by subcortical microstructure of the connections projecting from the subthalamic nucleus to the cortical regions of the network. Our findings extend current understanding of the role of white matter in childhood response inhibition.
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http://dx.doi.org/10.1016/j.cortex.2021.06.002DOI Listing
September 2021

Fatigue Following Pediatric Arterial Ischemic Stroke: Prevalence and Associated Factors.

Stroke 2021 Oct 28;52(10):3286-3295. Epub 2021 Jun 28.

Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia (M.G., A.C., S.H., R.W.H., M.T.M., P.M., V.A.).

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.033000DOI Listing
October 2021

Intra- and inter-hemispheric structural connectome in agenesis of the corpus callosum.

Neuroimage Clin 2021 5;31:102709. Epub 2021 Jun 5.

Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Switzerland; Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland; Brain and Mind Research, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Switzerland. Electronic address:

Agenesis of the corpus callosum (AgCC) is a congenital brain malformation characterized by the complete or partial failure to develop the corpus callosum. Despite missing the largest white matter bundle connecting the left and right hemispheres of the brain, studies have shown preserved inter-hemispheric communication in individuals with AgCC. It is likely that plasticity provides mechanisms for the brain to adjust in the context of AgCC, as the malformation disrupts programmed developmental brain processes very early on. A proposed candidate for neuroplastic response in individuals with AgCC is strengthening of intra-hemispheric structural connections. In the present study, we explore this hypothesis using a graph-based approach of the structural connectome, which enables intra- and inter-hemispheric analyses at multiple resolutions and quantification of structural characteristics through graph metrics. Structural graph metrics of 19 children with AgCC (13 with complete, 6 with partial AgCC) were compared to those of 29 typically developing controls (TDC). Associations between structural graph metrics and a wide range of neurobehavioral outcomes were examined using a multivariate data-driven approach (Partial Least Squares Correlation, PLSC). Our results provide new evidence suggesting structural strengthening of intra-hemispheric pathways as a neuroplastic response in the acallosal brain, and highlight regional variability in structural connectivity in children with AgCC compared to TDC. There was little evidence that structural graph properties in children with AgCC were associated with neurobehavioral outcomes. To our knowledge, this is the first report leveraging graph theory tools to explicitly characterize whole-brain intra- and inter-hemispheric structural connectivity in AgCC, opening avenues for future research on neuroplastic responses in AgCC.
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http://dx.doi.org/10.1016/j.nicl.2021.102709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209843PMC
September 2021

Revisiting brain rewiring and plasticity in children born without corpus callosum.

Dev Sci 2021 Nov 1;24(6):e13126. Epub 2021 Jun 1.

Medical Image Processing Lab, Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, Lausanne, VD, Switzerland.

The corpus callosum is the largest white matter pathway connecting homologous structures of the two cerebral hemispheres. Remarkably, children and adults with developmental absence of the corpus callosum (callosal dysgenesis, CD) show typical interhemispheric integration, which is classically impaired in adult split-brain patients, for whom the corpus callosum is surgically severed. Tovar-Moll and colleagues (2014) proposed alternative neural pathways involved in the preservation of interhemispheric transfer. In a sample of six adults with CD, they revealed two homotopic bundles crossing the midline via the anterior and posterior commissures and connecting parietal cortices, and the microstructural properties of these aberrant bundles were associated with functional connectivity of these regions. The aberrant bundles were specific to CD and not visualised in healthy brains. We extended this study in a developmental cohort of 20 children with CD and 29 typically developing controls (TDC). The two anomalous white-matter bundles were visualised using tractography. Associations between structural properties of these bundles and their regional functional connectivity were explored. The proposed atypical bundles were observed in 30% of our CD cohort crossing via the anterior commissure, and in 30% crossing via the posterior commissure (also observed in 6.9% of TDC). However, the structural property measures of these bundles were not associated with parietal functional connectivity, bringing into question their role and implication for interhemispheric functional connectivity in CD. It is possible that very early disruption of embryological callosal development enhances neuroplasticity and facilitates the formation of these proposed alternative neural pathways, but further evidence is needed.
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http://dx.doi.org/10.1111/desc.13126DOI Listing
November 2021

Associations between cognitive and affective empathy and internalizing symptoms in late childhood.

J Affect Disord 2021 07 25;290:245-253. Epub 2021 Apr 25.

Melbourne Neuropsychiatry Centre (MNC), Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, Australia.

Background: Empathy is a multidimensional construct, which includes cognitive and affective components. Studies in adults have demonstrated that both cognitive and affective empathy are associated with anxious and depressive symptoms. The aim of this study was to examine these associations in childhood.

Methods: Participants were 127 9- and 10-year-old children, recruited from the community. Self-report measures of cognitive and affective empathy, and internalizing symptoms were administered, as well as a task-based measure of cognitive empathy.

Results: Canonical correlation analysis demonstrated that components of affective empathy, specifically affective sharing and empathic distress, were associated with internalizing (particularly social anxiety) symptoms (R = 0.63, non-parametric p < .001). Cognitive empathy was not associated with internalizing symptoms.

Limitations: Most of our findings were based around self-report measures of empathy, which may not accurately reflect empathy ability.

Conclusions: Findings suggests that children who share each other's emotions strongly are more likely to experience anxiety, particularly of a social nature.
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http://dx.doi.org/10.1016/j.jad.2021.04.034DOI Listing
July 2021

Mental health after paediatric concussion: a systematic review and meta-analysis.

Br J Sports Med 2021 Sep 29;55(18):1048-1058. Epub 2021 Apr 29.

Brain and Mind Research, Clinical Sciences Theme, Murdoch Children's Research Institute, Parkville, Victoria, Australia

Objective: This systematic review and meta-analysis sought to rigorously examine mental health outcomes following paediatric concussion. To date, heterogeneous findings and methodologies have limited clinicians' and researchers' ability to meaningfully synthesise existing literature. In this context, there is a need to clarify mental health outcomes in a homogeneous sample, controlling for key methodological differences and applying a consistent definition of concussion across studies.

Design: Systematic review and meta-analysis.

Data Sources: We searched Medline, Embase, PsycINFO, CINAHL, SportDiscus, Scopus and PubMed.

Eligibility: Peer-reviewed studies published between 1980 and June 2020 that prospectively examined mental health outcomes after paediatric concussion, defined as per the Berlin Consensus Statement on Concussion in Sport.

Results: Sixty-nine articles characterising 60 unique samples met inclusion criteria, representing 89 114 children with concussion. Forty articles (33 studies) contributed to a random effects meta-analysis of internalising (withdrawal, anxiety, depression, post-traumatic stress), externalising (conduct problems, aggression, attention, hyperactivity) and total mental health difficulties across three time points post-injury (acute, persisting and chronic). Overall, children with concussion (n=6819) experienced significantly higher levels of internalising (g=0.41-0.46), externalising (g=0.25-0.46) and overall mental health difficulties compared with controls (g=0.18-0.49; n=56 271), with effects decreasing over time.

Summary/conclusions: Our review highlights that mental health is central to concussion recovery. Assessment, prevention and intervention of mental health status should be integrated into standard follow-up procedures. Further research is needed to clarify the mechanisms underlying observed relationships between mental health, post-concussion symptoms and other psychosocial factors. Results suggest that concussion may both precipitate and exacerbate mental health difficulties, thus impacting delayed recovery and psychosocial outcomes.
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http://dx.doi.org/10.1136/bjsports-2020-103548DOI Listing
September 2021

Preventing internalising problems in preschoolers with chronic physical health conditions.

J Child Health Care 2021 Apr 29:13674935211013192. Epub 2021 Apr 29.

School of Psychology and Public Health, 2080La Trobe University, Melbourne, Australia.

This pilot study aimed to explore the suitability of a preventative intervention for internalising problems in young children with chronic physical health conditions. The pilot study focused on a subsample of 27 children with chronic physical health conditions within a population-level randomised controlled trial of the Cool Little Kids parenting programme. The Cool Little Kids parenting programme aims to prevent the development of internalising problems in inhibited (shy/anxious) preschool children by educating parents to reduce young children's avoidant coping styles and manage their anxiety/distress. The wider trial recruited 545 temperamentally inhibited preschool children. Measures included child health/development concerns and internalising symptoms at baseline, feedback on Cool Little Kids post-intervention and child internalising problems at one- and two-year longitudinal follow-up. At baseline, inhibited children with and without chronic physical health conditions had levels of internalising symptoms above the normative mean. At post-intervention, parents of children with chronic physical health conditions gave feedback that Cool Little Kids was helpful for managing their child's emotional distress. At follow-up, significantly fewer intervention than control children with chronic physical health conditions had specific phobia after 1 year (25% vs 70%) and specific fear symptoms after 2 years (mean 9.57 vs 16.89). As the pilot findings are promising, a further trial of Cool Little Kids in a physical health treatment service with a larger sample of children with chronic physical illness diagnoses would be worthwhile.
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http://dx.doi.org/10.1177/13674935211013192DOI Listing
April 2021

Social Cognitive Dysfunction Following Pediatric Arterial Ischemic Stroke: Evidence From a Prospective Cohort Study.

Stroke 2021 May 8;52(5):1609-1617. Epub 2021 Apr 8.

Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia (N.P.R., M.G., L.C., A.C, L.C., R.W.H., P.M., M.T.M., V.A.).

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032955DOI Listing
May 2021

No Evidence of a Difference in Susceptibility-Weighted Imaging Lesion Burden or Functional Network Connectivity between Children with Typical and Delayed Recovery Two Weeks Post-Concussion.

J Neurotrauma 2021 Sep 30;38(17):2384-2390. Epub 2021 Jul 30.

Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Susceptibility weighted imaging (SWI) and resting state functional magnetic resonance imaging have been highlighted as two novel neuroimaging modalities that have been underutilized when attempting to predict whether a child with concussion will recover normally or have a delayed recovery course. This study aimed to investigate whether there was a difference between children who recover normally from a concussion and children with delayed recovery in terms of SWI lesion burden and resting state network makeup. Forty-one children who presented to the emergency department of a tertiary level pediatric hospital with concussion participated in this study as a part of a larger prospective, longitudinal observational cohort study into concussion assessment and recovery. Children underwent neuroimaging 2 weeks post-injury and were classified as either normally recovering ( = 27), or delayed recovering ( = 14) based on their post-concussion symptoms at 2 weeks post-injury. No participants showed lesions detected using SWI; therefore, no group differences could be assessed. No between-group resting state network differences were uncovered using dual regression analysis. These findings, alongside previously published work, suggest that potential causes of delayed recovery from concussion may not be found using current neuroimaging paradigms.
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http://dx.doi.org/10.1089/neu.2021.0069DOI Listing
September 2021

White matter tract signatures of fiber density and morphology in ADHD.

Cortex 2021 05 3;138:329-340. Epub 2021 Mar 3.

Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia; Developmental Imaging, Murdoch Children's Research Institute, Parkville, Australia.

Previous studies investigating white matter organization in attention deficit hyperactivity disorder (ADHD) have adopted diffusion tensor imaging (DTI). However, attempts to derive pathophysiological models from this research have had limited success, possibly reflecting limitations of the DTI method. This study investigated the organization of white matter tracts in ADHD using fixel based analysis (FBA), a fiber specific analysis framework that is well placed to provide novel insights into the pathophysiology of ADHD. High angular diffusion weighted imaging and clinical data were collected in a large paediatric cohort (N = 144; 76 with ADHD; age range 9-11 years). White matter tractography and FBA were performed across 14 white matter tracts. Permutation based inference testing (using FBA derived measures of fiber density and morphology) assessed differences in white matter tract profiles between children with and without ADHD. Analysis further examined the association between white matter properties and ADHD symptom severity. Relative to controls, children with ADHD showed reduced white matter connectivity along association and projection pathways considered critical to behavioral control and motor function. Increased ADHD symptom severity was associated with reduced white matter organization in fronto-pontine fibers projecting to and from the supplementary motor area. Providing novel insight into the neurobiological foundations of ADHD, this is the first research to uncover fiber specific white matter alterations across a comprehensive set of white matter tracts in ADHD using FBA. Findings inform pathophysiological models of ADHD and hold great promise for the consistent identification and systematic replication of brain differences in this disorder.
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http://dx.doi.org/10.1016/j.cortex.2021.02.015DOI Listing
May 2021

Validation of the SCAT5 and Child SCAT5 Word-List Memory Task.

J Neurotrauma 2021 May 10. Epub 2021 May 10.

Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

The Sports Concussion Assessment Tool-5th Edition (SCAT5) and the child version (Child SCAT5) are the current editions of the SCAT and have updated the memory testing component from previous editions. This study aimed to validate this new memory component against the Rey Auditory Verbal Learning Test (RAVLT) as the validated standard. This prospective, observational study, carried out within The Royal Children's Hospital Emergency Department, Melbourne, Australia, recruited 198 participants: 91 with concussion and 107 upper limb injury or healthy sibling controls. Partial Pearson correlations showed that memory acquisition and recall on delay aspects of the SCAT5 were significantly correlated with the RAVLT equivalents when controlling for age ( < 0.001,  = 0.565 and  < 0.001,  = 0.341, respectively). Factor analysis showed that all RAVLT and SCAT5 memory components load on to the same factor, accounting for 59.13% of variance. Logistic regression models for both the RAVLT and SCAT5, however, did not predict group membership ( > 0.05). Receiver operating curve analysis found that the area under the curve for all variables and models was below the recommended 0.7 threshold. This study demonstrated that the SCAT5 and Child SCAT5 memory paradigm is a valid measure of memory in concussed children.
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http://dx.doi.org/10.1089/neu.2020.7414DOI Listing
May 2021

Importance of accounting for sibling age when examining the association between family size and early childhood cognition, language and emotional behaviour: a birth cohort study.

BMJ Open 2021 03 19;11(3):e041984. Epub 2021 Mar 19.

Murdoch Children's Research Institute,Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia

Objectives: Larger sibships are associated with poorer cognitive and language outcomes but have different impacts on child emotional development. Previous studies have not taken into account sibling age, nor have impacts across multiple neurodevelopmental domains been considered in the same participant group. This study investigated the influence of family size indicators on early childhood cognitive, language and emotional-behavioural development. The effect of sibling age was considered by evaluating these relationships separately for different sibling age categories.

Design: Prospective birth cohort study.

Setting: Participants in the Barwon Infant Study were recruited from two major hospitals in the Barwon region of Victoria, Australia, between 2010 and 2013 (n=1074 children).

Participants: The 755 children with any neurodevelopmental data at age 2-3 years excluding twins and those with an acquired neurodisability.

Outcome Measures: Cognitive and language development was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition, and emotional-behavioural development was measured with the Child Behaviour Checklist for Ages 1½-5.

Results: Greater household size was associated with a reduced cognitive development score (adjusted mean difference (AMD) -0.66 per extra household member; 95% CI -0.96 to -0.37; p<0.001) without age-specific differences. However, poorer expressive language was only observed for exposure to siblings between 2-6 and 6-10 years older. Having siblings 2-6 years older was associated with less internalising behaviour (AMD -2.1 per sibling; 95% CI -3.1 to -1.0; p<0.001). These associations persisted after multiple comparison adjustment.

Conclusions: The influence of siblings on early childhood development varies substantially by sibling age and the neurodevelopmental outcome under study. Although family size alone appears important for cognitive development, age-specific findings emphasise the importance of sibling interaction in early childhood expressive language development and emotional behaviour.
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http://dx.doi.org/10.1136/bmjopen-2020-041984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986776PMC
March 2021

Executive function mediates the prospective association between neurostructural differences within the central executive network and anti-social behavior after childhood traumatic brain injury.

J Child Psychol Psychiatry 2021 Sep 24;62(9):1150-1161. Epub 2021 Feb 24.

Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Vic., Australia.

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.
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http://dx.doi.org/10.1111/jcpp.13385DOI Listing
September 2021

Protocol for a randomised clinical trial of multimodal postconcussion symptom treatment and recovery: the Concussion Essentials study.

BMJ Open 2021 02 11;11(2):e041458. Epub 2021 Feb 11.

Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Introduction: While most children recover from a concussion shortly after injury, approximately 30% experience persistent postconcussive symptoms (pPCS) beyond 1-month postinjury. Existing research into the treatment of pPCS have evaluated unimodal approaches, despite evidence suggesting that pPCS likely represent an interaction across various symptom clusters. The primary aim of this study is to evaluate the effectiveness of a multimodal, symptom-tailored intervention to accelerate symptom recovery and increase the proportion of children with resolved symptoms at 3 months postconcussion.

Methods And Analysis: In this open-label, assessor-blinded, randomised clinical trial, children with concussion aged 8-18 years will be recruited from The Royal Children's Hospital (The RCH) emergency department, or referred by a clinician, within 17 days of initial injury. Based on parent ratings of their child's PCS at ~10 days postinjury, symptomatic children (≥2 symptoms at least 1-point above those endorsed preinjury) will undergo a baseline assessment at 3 weeks postinjury and randomised into either Concussion Essentials (CE, n=108), a multimodal, interdisciplinary delivered, symptom-tailored treatment involving physiotherapy, psychology and education, or usual care (UC, n=108) study arms. CE participants will receive 1 hour of intervention each week, for up to 8 weeks or until pPCS resolve. A postprogramme assessment will be conducted at 3 months postinjury for all participants. Effectiveness of the CE intervention will be determined by the proportion of participants for whom pPCS have resolved at the postprogramme assessment (primary outcome) relative to the UC group. Secondary outcome analyses will examine whether children receiving CE are more likely to demonstrate resolution of pPCS, earlier return to normal activity, higher quality of life and a lower rate of utilisation of health services, compared with the UC group.

Ethics And Dissemination: Ethics were approved by The RCH Human Research Ethics Committee (HREC: 37100). Parent, and for mature minors, participant consent, will be obtained prior to commencement of the trial. Study results will be disseminated at international conferences and international peer-reviewed journals.

Trial Registration Number: ACTRN12617000418370; pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880104PMC
February 2021

Australian and New Zealand Guideline for Mild to Moderate Head Injuries in Children.

Emerg Med Australas 2021 04 2;33(2):214-231. Epub 2021 Feb 2.

Children's Emergency Department, Starship Children's Hospital, Auckland, New Zealand.

Objective: Children frequently present with head injuries to acute care settings. Although international paediatric clinical practice guidelines for head injuries exist, they do not address all considerations related to triage, imaging, observation versus admission, transfer, discharge and follow-up of mild to moderate head injuries relevant to the Australian and New Zealand context. The Paediatric Research in Emergency Departments International Collaborative (PREDICT) set out to develop an evidence-based, locally applicable, practical clinical guideline for the care of children with mild to moderate head injuries presenting to acute care settings.

Methods: A multidisciplinary Guideline Working Group (GWG) developed 33 questions in three key areas - triage, imaging and discharge of children with mild to moderate head injuries presenting to acute care settings. We identified existing high-quality guidelines and from these guidelines recommendations were mapped to clinical questions. Updated literature searches were undertaken, and key new evidence identified. Recommendations were created through either adoption, adaptation or development of de novo recommendations. The guideline was revised after a period of public consultation.

Results: The GWG developed 71 recommendations (evidence-informed = 35, consensus-based = 17, practice points = 19), relevant to the Australian and New Zealand setting. The guideline is presented as three documents: (i) a detailed Full Guideline summarising the evidence underlying each recommendation; (ii) a Guideline Summary; and (iii) a clinical Algorithm: Imaging and Observation Decision-making for Children with Head Injuries.

Conclusions: The PREDICT Australian and New Zealand Guideline for Mild to Moderate Head Injuries in Children provides high-level evidence and practical guidance for front line clinicians.
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http://dx.doi.org/10.1111/1742-6723.13722DOI Listing
April 2021

Lesion Induced Error on Automated Measures of Brain Volume: Data From a Pediatric Traumatic Brain Injury Cohort.

Front Neurosci 2020 30;14:491478. Epub 2020 Nov 30.

College of Health and Life Sciences, Aston Institute of Health and Neurodevelopment, Aston University, Birmingham, United Kingdom.

Structural segmentation of T1-weighted (T1w) MRI has shown morphometric differences, both compared to controls and longitudinally, following a traumatic brain injury (TBI). While many patients with TBI present with abnormalities on structural MRI images, most neuroimaging software packages have not been systematically evaluated for accuracy in the presence of these pathology-related MRI abnormalities. The current study aimed to assess whether acute MRI lesions (MRI acquired 7-71 days post-injury) cause error in the estimates of brain volume produced by the semi-automated segmentation tool, Freesurfer. More specifically, to investigate whether this error was global, the presence of lesion-induced error in the contralesional hemisphere, where no abnormal signal was present, was measured. A dataset of 176 simulated lesion cases was generated using actual lesions from 16 pediatric TBI (pTBI) cases recruited from the emergency department and 11 typically-developing controls. Simulated lesion cases were compared to the "ground truth" of the non-lesion control-case T1w images. Using linear mixed-effects models, results showed that hemispheric measures of cortex volume were significantly lower in the contralesional-hemisphere compared to the ground truth. Interestingly, however, cortex volume (and cerebral white matter volume) were not significantly different in the lesioned hemisphere. However, percent volume difference (PVD) between the simulated lesion and ground truth showed that the magnitude of difference of cortex volume in the contralesional-hemisphere (mean PVD = 0.37%) was significantly smaller than that in the lesioned hemisphere (mean PVD = 0.47%), suggesting a small, but systematic lesion-induced error. Lesion characteristics that could explain variance in the PVD for each hemisphere were investigated. Taken together, these results suggest that the lesion-induced error caused by simulated lesions was not focal, but globally distributed. Previous post-processing approaches to adjust for lesions in structural analyses address the focal region where the lesion was located however, our results suggest that focal correction approaches are insufficient for the global error in morphometric measures of the injured brain.
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http://dx.doi.org/10.3389/fnins.2020.491478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793828PMC
November 2020

A longitudinal analysis of puberty-related cortical development.

Neuroimage 2021 03 29;228:117684. Epub 2020 Dec 29.

School of Psychology, Deakin University, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; Developmental Imaging, Murdoch Children's Research Institute, Parkville, Australia.

The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether individual differences in the rate of pubertal maturation (or "pubertal tempo") was associated with variations in cortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important individual differences in the coupling of these developmental processes.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117684DOI Listing
March 2021

A longitudinal analysis of puberty-related cortical development.

Neuroimage 2021 03 29;228:117684. Epub 2020 Dec 29.

School of Psychology, Deakin University, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; Developmental Imaging, Murdoch Children's Research Institute, Parkville, Australia.

The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether individual differences in the rate of pubertal maturation (or "pubertal tempo") was associated with variations in cortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important individual differences in the coupling of these developmental processes.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117684DOI Listing
March 2021

Predictors of participation and quality of life following major traumatic injuries in childhood: a systematic review.

Disabil Rehabil 2020 Nov 24:1-17. Epub 2020 Nov 24.

Murdoch Children's Research Institute, Parkville, VIC, Australia.

Objective: Review the literature on predictors of participation and quality of life in children and young people who sustained a traumatic brain injury (TBI), spinal cord injury (SCI), and/or multi-trauma in a motor vehicle or other accident or trauma.

Design: This systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol was registered on PROSPERO (registration number CRD42020131698). Electronic databases were searched for studies published between January 2000 and August 2020. Prospective and retrospective cohort studies were considered and risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool.

Results: The search yielded 5771 articles of which 30 studies met the inclusion criteria. Nineteen studies included patients with TBI and 11 with SCI. No studies of patients with multi-trauma met criteria. Evidence was found for associations with various factors (e.g., injury severity, level of education, mental health problems), although these findings are limited due to the quality of the studies (5 studies moderate and 25 high risk of bias).

Conclusion: Research on predictors of participation and quality of life following major traumatic injuries in childhood is lacking. More methodologically sound prospective, longitudinal studies are needed across different injury groups to further elucidate predictors of outcome.IMPLICATIONS FOR REHABILITATIONWhile long-term participation and quality of life is influenced by injury characteristics (i.e., injury severity), a number of potential modifiable factors can be targeted to improve outcomes following traumatic injuries in childhood.Young people should be provided with support to stay in school and pursue further education.Early intervention and prevention of mental health problems may improve long-term outcomes.Better management of ongoing medical problems and greater support for functional independence may improve participation.
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http://dx.doi.org/10.1080/09638288.2020.1849425DOI Listing
November 2020

Long-Term Intellectual Function After Traumatic Brain Injury in Very Young Children.

J Head Trauma Rehabil 2021 Mar-Apr 01;36(2):E126-E133

Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia (Drs Crowe, Catroppa, Babl, Godfrey, and Anderson); School of Psychological Science, University of Melbourne, Melbourne, Victoria, Australia (Drs Crowe, Godfrey, and Anderson); and Psychology Service (Drs Crowe, Godfrey, and Anderson) and Emergency Department (Dr Babl), Royal Children's Hospital, Melbourne, Victoria, Australia.

Objective: To investigate long-term intellectual function following a traumatic brain injury (TBI) in early childhood and to identify the contribution of injury and environment to outcome.

Participants: Fifty children younger than 3 years with a diagnosis of accidental TBI were recruited through a pediatric hospital emergency department. Children with TBI were compared with a group (n = 33) of typically developing children (TDC) matched on demographics.

Design: Longitudinal, single-site, case-control study.

Measures: Children completed intellectual assessments (IQ) at 4.5 to 5.5 years of age (average 3.5 years after TBI) and at 7.5 to 9 years of age (average 6.5 years after TBI). Information on injury and environmental predictors of outcome was collected.

Results: IQ scores for all groups were in the average range; however, children with TBI of any severity had lower scores than TDC at both time points. There was some suggestion of children with TBI achieving lower verbal IQ scores over time than TDC. IQ scores were predicted by family environment, not injury characteristics.

Conclusions: A TBI in early childhood is associated with lower IQ scores that persist several years postinjury. Socioeconomic status is an influential factor on IQ at 6.5 years post-TBI.
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http://dx.doi.org/10.1097/HTR.0000000000000626DOI Listing
October 2021

Social competence in early childhood: An empirical validation of the SOCIAL model.

J Neuropsychol 2021 Sep 6;15(3):477-499. Epub 2020 Nov 6.

Department of Psychology, University of Montreal, Montreal, Quebec, Canada.

Social skills are the basis of human interactions and functioning in society. Social competence (SC) is thought to evolve gradually during childhood and adolescence via the interplay of multiple factors. In particular, the early years of life are marked by the emergence of basic social abilities and constitute the foundation for successful social development. The biopsychosocial SOcio-Cognitive Integration of Abilities modeL (SOCIAL) posits that internal (child-based), external (environment), and cognitive factors are critical to SC in the context of normal brain maturation; but this has yet to be shown empirically and comprehensively. This study tested the SOCIAL model in a sample of typically developing preschool children. Parents of 103 children (M = 67.59 months, SD = 11.65) completed questionnaires and children underwent neuropsychological assessment of executive functioning (EF), communication skills and social cognition. Three-step hierarchical regression analyses (1) Internal factors, 2) External factors, 3) Cognitive factors) confirmed that each step of the regression model significantly predicted SC. In the final model, general cognitive and socio-cognitive factors significantly predicted SC above and beyond internal and external factors: children with lower temperamental negative affect and less parent-reported executive dysfunction, as well as better non-verbal communication and theory of mind had better SC. Our findings support the conceptual SOCIAL model, and highlight the importance of internal, external, and cognitive factors for SC in the preschool years. Identification of factors associated with early social development can inform both normative and clinical approaches to identifying intervention loci and optimizing SC in those at risk for maladaptive social functioning.
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http://dx.doi.org/10.1111/jnp.12230DOI Listing
September 2021
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