Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

OBJECTIVES: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC). METHODS: Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. RESULTS: The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. CONCLUSIONS: This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Adolescents with ADHD and co-occurring motor difficulties show a distinct pattern of maturation within the corticospinal tract from those without: A longitudinal fixel-based study.

It is well documented that attention-deficit hyperactivity disorder (ADHD) often presents with co-occurring motor difficulties. However, little is known about the biological mechanisms that explain compromised motor skills in approximately half of those with ADHD. To provide insight into the neurobiological basis of poor motor outcomes in ADHD, this study profiled the development of white matter organization within the cortico-spinal tract (CST) in adolescents with ADHD with and without co-occurring motor problems, as well as non-ADHD control children with and without motor problems. Participants were 60 children aged 9-14 years, 27 with a history of ADHD and 33 controls. All underwent high-angular resolution diffusion MRI data at up to three time points (115 in scans total). We screened for motor impairment in all participants at the third time point (≈14 years) using the Developmental Coordination Disorder Questionnaire (DCD-Q). Following pre-processing of diffusion MRI scans, fixel-based analysis was performed, and the bilateral CST was delineated using TractSeg. Mean fiber density (FD) and fiber cross-section (FC) were extracted for each tract at each time-point. To investigate longitudinal trajectories of fiber development, linear mixed models were performed separately for the left and right CST, controlling for nuisance variables. To examine possible variations in fiber development between groups, we tested whether the inclusion of group and the interaction between age and group improved model fit. At ≈10 years, those with ADHD presented with lower FD within the bilateral CST relative to controls, irrespective of their prospective motor status. While these microstructural abnormalities persisted into adolescence for individuals with ADHD and co-occurring motor problems, they resolved for those with ADHD alone. Divergent maturational pathways of motor networks (i.e., the CST) may, at least partly, explain motor problems individuals with ADHD.

Association of neurostructural biomarkers with secondary attention-deficit/hyperactivity disorder (ADHD) symptom severity in children with traumatic brain injury: a prospective cohort study.

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.

Categorical and dimensional approaches to the developmental relationship between ADHD and irritability.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and irritability commonly co-occur, and follow similar developmental trajectories from childhood to adolescence. Understanding of the developmental relationship between these co-occurrences is limited. This study provides a longitudinal assessment of how ADHD diagnostic status and symptom patterns predict change in irritability. METHODS: A community sample of 337 participants (45.2% ADHD), recruited for the Childhood Attention Project, completed the Affective Reactivity Index (ARI) to measure irritability at baseline (mean age 10.5 years) and follow-up after 18-months. Latent change score models were used to assess how (a) baseline ADHD vs. control group status, (b) baseline symptom domain (inattention, hyperactivity-impulsivity) and (c) longitudinal change in ADHD symptom severity predicted change in irritability. RESULTS: Irritability was significantly higher among the ADHD group than controls; however, change in irritability over time did not differ between groups. When assessed across the entire cohort, change in irritability was predicted by higher symptom count in the hyperactive-impulsive domain, but not the inattentive domain. Greater declines in ADHD symptoms over time significantly predicted greater declines in irritability. Baseline ADHD symptom severity was found to significantly predict change in irritability; however, baseline irritability did not significantly predict change in ADHD symptoms. CONCLUSIONS: ADHD symptoms-particularly hyperactive-impulsive symptoms-predict the degree and trajectory of irritability during childhood and adolescence, even when symptoms are below diagnostic thresholds. The use of longitudinal, dimensional and symptom domain-specific measures provides additional insight into this relationship.

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

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.

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

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.

Cognitive, behavioral, and social functioning in children and adults with Dravet syndrome.

AIM: The objective of the study was to delineate the cognitive, behavioral, psychological, and social functioning of individuals with Dravet syndrome. METHOD: Cognitive, behavioral, and social functioning were assessed in patients with Dravet syndrome by comprehensive, age-appropriate standardized neuropsychological testing. Primary caregivers completed standardized measures regarding participants' behavior, psychological status, adaptive functioning, and social skills, including their involvement with intervention services. RESULTS: The cohort comprised 45 patients, aged 2-30 years. Intellectual functioning ranged from average intellect to profound intellectual disability, with a decrease in cognitive and adaptive functioning with age. Only 6 children were able to complete the entire neuropsychological battery and showed a range of cognitive profiles. Five of 6 participants scored within the average range on Affect Recognition and 5/6 on Motor Free Visual Perception tests. Twenty-one (58%) participants had deficits in social skills and 18/27 (67%) in social communication, with 10 participants, who did not yet have a diagnosis of autism spectrum disorder (ASD), screening positive for social communication deficits. Behavioral problems were frequently reported, with attention problems in 24 (65%) and atypicality in 25 (70%). Despite this, parents reported that psychological services were the least utilized health interventions. CONCLUSIONS: Cognitive functioning varies markedly in individuals with Dravet syndrome, with some patients demonstrating global impairment while others have a discordant neuropsychological profile. Behavioral, psychological, social problems, and ASD are common. Social deficits should be reviewed to identify those who warrant ASD assessment. Early identification of behavioral and psychological disorders and targeted use of psychological intervention are essential components of holistic care in Dravet syndrome.

Sleep Disturbances in Young Adults with Childhood Traumatic Brain Injury: Relationship with Fatigue, Depression, and Quality of Life.

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.

Social Function and Autism Spectrum Disorder in Children and Adults with Neurofibromatosis Type 1: a Systematic Review and Meta-Analysis.

In light of the proliferation of recent research into social function in neurofibromatosis type 1 (NF1), a systematic review and meta-analysis is required to synthesise data and place findings within the context of a theoretical framework. This paper reviews findings from research into social function and autism spectrum disorder (ASD) in children and adults with NF1 and integrates these findings with the Socio-Cognitive Integration Abilities Model (SOCIAL). It also critically appraises links between social outcomes, internal and external factors moderating social functioning, cognitive domains implicated in social functioning, and underlying neural pathology in NF1. A systematic literature search conducted in MedLine (Ovid), PsycINFO (Ovid), Embase (Ovid), and PubMed electronic databases yielded 35 papers that met inclusion criteria for the systematic review. Out of these papers, 22 papers provided sufficient data for meta-analysis. Findings from this review and meta-analysis provide evidence that children and adults with NF1 exhibit significantly higher prevalence and severity of social dysfunction and ASD symptomatology. To date, very few studies have examined social cognition in NF1 but results indicate the presence of both perceptual and higher-level impairments in this population. The results of this review also provide support for age, gender, and comorbid ADHD as moderating factors for social outcomes in NF1. Suggestions for future research are offered to further our understanding of the social phenotype in NF1 and to facilitate the development of targeted interventions.

Featured Article: Trajectories of Posttraumatic Stress Symptoms in Parents of Children With a Serious Childhood Illness or Injury.

Objective: Serious childhood illness is associated with significant parent psychological distress. This study aimed to (a) document acute and posttraumatic stress symptoms (PTSS) in parents of children with various life-threatening illnesses; (b) identify trajectory patterns of parental PTSS and recovery over 18 months; (c) determine psychosocial, demographic, and illness factors associated with trajectory group membership. Methods: In total, 159 parents (115 mothers, 44 fathers) from 122 families participated in a prospective, longitudinal study that assessed parent psychological responses across four time points-at diagnosis, and 3, 6, and 18 months later. Children were admitted to the Cardiology, Oncology, and Pediatric Intensive Care Departments in a tertiary pediatric hospital. The primary outcome was parent PTSS. Results: Three distinct parent recovery profiles were identified-"Resilient," "Recovery," and "Chronic." The "Resilient" class (33%) showed low distress responses across the trajectory period, whereas the "Recovery" class (52%) showed significantly higher levels of distress at the time of diagnosis that gradually declined over the first months following their child's illness. Both of these classes nevertheless remained within the normative range throughout. In contrast, the "Chronic" class (13%) was consistently high in severity, remaining within the clinical range across the entire period. Psychosocial factors such as mood, anxiety, and emotional responses predicted group membership, whereas demographic and illness factors did not. Conclusions: Parents show considerable resilience in the face of children's life-threatening illnesses. Early assessment of parent psychosocial factors may aid identification of those who would benefit from early intervention.

Prediction of Multidimensional Fatigue After Childhood Brain Injury.

OBJECTIVES: To determine (1) the presence of fatigue symptoms and predictors of fatigue after childhood brain injury and examine (2) the feasibility, reliability, and validity of a multidimensional fatigue measure (PedsQL Multidimensional Fatigue Scale [MFS]) obtained from parent and child perspectives. SETTING: Emergency and intensive care units of a hospital in Melbourne, Australia. PARTICIPANTS: Thirty-five families (34 parent-proxies and 32 children) aged 8 to 18 years (mean child age = 13.29 years) with traumatic brain injury (TBI) of all severities (27 mild, 5 moderate, and 3 severe) admitted to the Royal Children's Hospital. DESIGN: Longitudinal prospective study. Fatigue data collected at 6-week follow-up (mean = 6.9 weeks). MAIN OUTCOME MEASURES: Postinjury child- and parent-rated fatigue (PedsQL MFS), mood, sleep, and pain based on questionnaire report: TBI severity (mild vs moderate/severe TBI). RESULTS: A score greater than 2 standard deviations below healthy control data indicated the presence of abnormal fatigue, rates of which were higher compared with normative data for both parent and child reports (47% and 29%). Fatigue was predicted by postinjury depression and sleep disturbance for parent, but not child ratings. Fatigue, as rated by children, was not significantly predicted by TBI severity or other symptoms. The PedsQL MFS demonstrated acceptable measurement properties in child TBI participants, evidenced by good feasibility and reliability (Cronbach α values >0.90). Interrater reliability between parent and child reports was poor to moderate. CONCLUSIONS: Results underscore the need to assess fatigue and associated sleep-wake disturbance and depression after child TBI from both parent and child perspectives.

Psychosocial, Demographic, and Illness-Related Factors Associated With Acute Traumatic Stress Responses in Parents of Children With a Serious Illness or Injury.

This study investigated factors associated with acute stress symptoms in parents of seriously ill children across a range of illnesses and treatment settings within a pediatric hospital setting. It was hypothesized that psychosocial variables would be more strongly associated with acute stress responses than demographic and child illness variables. Participants were 115 mothers and 56 fathers of children treated within the oncology, cardiology, and intensive care departments of a pediatric hospital. Acute stress, psychosocial, demographic, and medical data were collected within the first 4 weeks of the child's hospital admission. A robust hierarchical regression model revealed that psychosocial factors significantly explained 36.8% of the variance in parent acute stress responses (p < .001); demographic variables significantly added a further 4.5% (p = .022), but illness-related factors did not contribute to the model. Findings support the implementation of a general psychosocial screening approach for parents across the wider hospital system, and that psychosocial risk factors may be targeted in interventions across different illnesses and treatment settings to improve parent outcomes.

Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery.

Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery-related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI-based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530-3543, 2016. © 2016 Wiley Periodicals, Inc.

Family Psychosocial Risk Screening in Infants and Older Children in the Acute Pediatric Hospital Setting Using the Psychosocial Assessment Tool.

OBJECTIVE: To examine the validity of the Psychosocial Assessment Tool (PAT) with families of infants (<2 years) and children admitted to hospital with acute life-threatening illnesses. METHODS: A total of 235 parents of 177 children admitted to oncology, cardiology, or pediatric intensive care completed the PAT and measures of acute stress, trait anxiety, family functioning, and quality of life, a mean 3.7 weeks following diagnosis. A modified PAT was used for families of infants, rendering two forms, PAT (<2) and PAT (2+). RESULTS: Psychometrics for PAT (<2) and PAT (2+) were acceptable. PAT Total and Subscale scores for each version were significantly correlated with validation measures. Internal consistency for PAT subscales was variable. Receiver Operating Characteristics provided some support for PAT cutoffs. PAT scores across illness groups were comparable. CONCLUSIONS: This study provides promising support for the PAT as a psychosocial screener for families of infants and older children across illness conditions.

Take A Breath: study protocol for a randomized controlled trial of an online group intervention to reduce traumatic stress in parents of children with a life threatening illness or injury.

BACKGROUND: A substantial proportion of parents whose child is diagnosed with a life-threatening illness, experience high levels of distress that can lead to long-term difficulties in mental health, family functioning and child adjustment. This study evaluates the efficacy of an Acceptance Commitment Therapy-based group intervention designed to reduce distress symptoms in these parents. The program is delivered using videoconferencing to overcome factors that prevent participation in traditional face-to-face therapy. METHOD/DESIGN: The study is a randomized control trial of the Take A Breath group intervention for parents demonstrating elevated symptoms of acute stress, delivered via videoconferencing in six 90 min group sessions. Participants are the primary caregivers of children aged 0 to 18 years admitted for a life threatening illness or injury to the Oncology, Cardiology, Neurology or Intensive Care Departments of a tertiary pediatric hospital. Parents will be randomized to intervention or waitlist control 4-10 months after their child's diagnosis. Measures will be collected prior to and immediately post intervention for intervention and waitlist parents to assess program efficacy. Intervention parents will be followed up at 6 months to assess the maintenance of program effects. We predict that intervention parents will show fewer symptoms post intervention than waitlist parents (primary outcomes: traumatic stress, depression, anxiety, stress symptoms), reflecting improvements in the psychological skills addressed in the intervention (mediating factors). It is anticipated that reductions in mental health difficulties for intervention parents will be maintained up to 6 months post-intervention and will be associated with broader improvements in parents' adjustment, child adjustment and child wellbeing (secondary outcomes). DISCUSSION: This study is unique in evaluating a group intervention delivered to parents of children affected by of a diverse range life-threatening illness or injury. Online communication technology is employed to reduce participation barriers. If proven efficacious, this trans-diagnostic approach offers the potential for broad use as part of the suite of psychosocial services provided to families through tertiary pediatric settings. TRIAL REGISTRATION: ACTRN12611000090910 . Trial Registration Date: 14/09/2011 Protocol Date/version: September 2015, version M Study Status: Ongoing.

Early Traumatic Stress Responses in Parents Following a Serious Illness in Their Child: A Systematic Review.

A systematic review of the literature investigating the early traumatic stress responses in parents of children diagnosed with a serious illness/injury. A literature review was conducted (September 2013) using Medline, PsycINFO, and CINAHL databases. Twenty-four studies related to parents of children hospitalized due to diagnosis of cancer, type 1 diabetes, meningococcal disease, trauma or serious injury, preterm birth and other serious illnesses requiring admission to intensive care were included. Parents were assessed for early traumatic stress symptoms within 3 months of their child's diagnosis/hospitalization. Prevalence rates of acute stress disorder in parents ranged from 12 to 63%. Prevalence of posttraumatic stress disorder ranged from 8 to 68%. Variability was related to methodological factors including differences in study design, timing of assessments, measurement tools, and scoring protocols. Psychosocial factors rather than medical factors predicted parent distress. This review integrates and compares early traumatic reactions in parents with children suffering a range of serious illnesses. Findings suggest a high prevalence of acute and posttraumatic stress symptoms in parents. Methodological inconsistencies made comparison of early traumatic stress prevalence rates difficult. Risk factors associated with traumatic stress symptoms were identified.

The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: a longitudinal prospective analysis using susceptibility-weighted imaging.

Childhood and adolescence are critical periods for maturation of neurobiological processes that underlie complex social and emotional behavior including Theory of Mind (ToM). While structural correlates of ToM are well described in adults, less is known about the anatomical regions subsuming these skills in the developing brain or the impact of cerebral insult on the acquisition and establishment of high-level social cognitive skills. This study aimed to examine the differential influence of age-at-insult and brain pathology on ToM in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with TBI (n = 112) were categorized according to timing of brain insult: (i) middle childhood (5-9 years; n = 41); (ii) late childhood (10-11 years; n = 39); and (iii) adolescence (12-15 years; n = 32) and group-matched for age, gender, and socioeconomic status to a typically developing (TD) control group (n = 43). Participants underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks postinjury and were assessed on a battery of ToM tasks at 6- and 24-months after injury. Results showed that for adolescents with TBI, social cognitive dysfunction at 6- and 24-months postinjury was associated with diffuse neuropathology and a greater number of lesions detected using SWI. In the late childhood TBI group, we found a time-dependent emergence of social cognitive impairment, linked to diffuse neuropathology. The middle childhood TBI group demonstrated performance unrelated to SWI pathology and comparable to TD controls. Findings indicate that the full extent of social cognitive deficits may not be realized until the associated skills reach maturity. Evidence for brain structure-function relationships suggests that the integrity of an anatomically distributed network of brain regions and their connections is necessary for the acquisition and establishment of high-level social cognitive skills.

Parent distress reactions following a serious illness or injury in their child: a protocol paper for the take a Breath Cohort Study.

BACKGROUND: Diagnosis of life threatening childhood illness or injury can lead to significant distress reactions in parents, with many experiencing clinically significant levels of post-traumatic stress symptoms. These symptoms can have long-term adverse impacts on parent mental health, family functioning, and the adjustment of the ill child. Independent studies have found such reactions in several different illness groups. However, very little research has systematically compared the prevalence, impact and trajectories over time of post-traumatic stress symptoms in parents across different childhood illness groups with an acute life threat. The current study seeks to map the course of post-traumatic stress reactions in parents of children with various life threatening illnesses over an 18 month period, and identify factors that predict successful adaptation in families. METHOD/DESIGN: The current study described is of a prospective, longitudinal design. The sample included parents of children admitted to four major hospital departments at the Royal Children's Hospital, Melbourne, Australia, for a life threatening illness or injury. Eligible parents were those who were caregivers of children aged 0-to 18-years admitted to the Oncology, Cardiology, Neurology and Pediatric Intensive Care Unit. Parents were recruited acutely, and completed self-report questionnaires at four time-points: within the first 4 weeks (T1:); then at 4 months (T2); 7 months (T3); and 19 months (T4) after admission. Questionnaires assessed parent and child mental health and wellbeing, and a number of risk and reliance factors such child illness factors, parent demographic factors, and psychosocial factors. DISCUSSION: This study is one of the first to document the trajectory of post-traumatic stress responses in parents of very ill children, across illness groups. Given that it will also identify risk and resilience factors, and map the course of parent outcomes over an 18 monthperiod, it has the potential to inform novel strategies for intervention.

Prevalence and predictors of externalizing behavior in young adult survivors of pediatric traumatic brain injury.

OBJECTIVES: To investigate rates of clinically significant externalizing behavior (EB) in young adult survivors of pediatric traumatic brain injury (TBI) and evaluate the contribution of pre- and postinjury risk and resilience factors to EB outcomes 16 years after injury. SETTING: Melbourne, Australia. PARTICIPANTS: Fifty-five young adults (mean age = 23.85 years; injury age: 1.0-12 years) admitted to an emergency department following TBI between 1993 and 1997. DESIGN: Longitudinal prospective study with data collected at the acute, 10-year, and 16-year postinjury time points. MAIN MEASURES: Severity of TBI, adaptive functioning, family functioning, full-scale IQ, executive functioning, social communication, and symptoms of EB. RESULTS: One of every 4 young people with a history of pediatric TBI demonstrated clinical or subthreshold levels of EB in young adulthood. More frequent EB was associated with poorer preinjury adaptive functioning, lower full-scale IQ, and more frequent pragmatic communication difficulty. CONCLUSION: Pediatric TBI is associated with an elevated risk for externalizing disorders in the transition to adulthood. Results underscore the need for screening and assessment of TBI among young offenders and suggest that early and long-term targeted interventions may be required to address risk factors for EB in children and young people with TBI.

Regional brain morphometric characteristics of nonsyndromic cleft lip and palate.

Nonsyndromic cleft lip and palate (NSCLP) encompasses a group of orofacial abnormalities. Emerging evidence has revealed the presence of structural brain abnormalities in affected individuals. Previous studies have performed structure-based volumetric analysis of the brain assessing gross lobular subdivisions of the cerebral cortex and white matter which may have only vague relationships to the functional subregions implicated in behavioral and cognitive deficits observed in NSCLP patients. High-resolution magnetic resonance imaging structural data were acquired to provide a detailed characterization of the brain with respect to both regional cortical volume and thickness in 26 children with NSCLP and 26 age- and demographically matched typically developing children. Children with NSCLP exhibited abnormally large cerebral cortex grey matter volumes with decreased volumes of subcortical grey matter and cerebral white matter structures. Hemisphere-specific patterns of cortical volume and thickness abnormalities were identified. This study is the first to examine cortical thickness abnormalities in NSCLP. Overall, these findings suggest that the brains of children with NSCLP are less mature than those of their age-matched peers. Gender-specific comparisons reveal that NSCLP females were more immature compared to their typically developing peers compared to NSCLP males.