Nicholas P. Ryan

Social communication mediates the relationship between emotion perception and externalizing behaviors in young adult survivors of pediatric traumatic brain injury (TBI)

Traumatic brain injury (TBI) is a common cause of childhood disability, and is associated with elevated risk for long‐term social impairment. Though social (pragmatic) communication deficits may be among the most debilitating consequences of childhood TBI, few studies have examined very long‐term communication outcomes as children with TBI make the transition to young adulthood. In addition, the extent to which reduced social function contributes to externalizing behaviors in survivors of childhood TBI remains poorly understood. The present study aimed to evaluate the extent of social communication difficulty among young adult survivors of childhood TBI (n = 34, injury age: 1.0–7.0 years; M time since injury: 16.55 years) and examine relations among aspects of social function including emotion perception, social communication and externalizing behaviors rated by close‐other proxies. Compared to controls the TBI group had significantly greater social communication difficulty, which was associated with more frequent externalizing behaviors and poorer emotion perception. Analyses demonstrated that reduced social communication mediated the association between poorer emotion perception and more frequent externalizing behaviors. Our findings indicate that socio‐cognitive impairments may indirectly increase the risk for externalizing behaviors among young adult survivors of childhood TBI, and underscore the need for targeted social skills interventions delivered soon after injury, and into the very long‐term.

Longitudinal outcome and recovery of social problems after pediatric traumatic brain injury (TBI): Contribution of brain insult and family environment

Pediatric traumatic brain injury (TBI) can result in a range of social impairments, however longitudinal recovery is not well characterized, and clinicians are poorly equipped to identify children at risk for persisting difficulties. Using a longitudinal prospective design, this study aimed to evaluate the contribution of injury and non‐injury related risk and resilience factors to longitudinal outcome and recovery of social problems from 12‐ to 24‐months post‐TBI. 78 children with TBI (injury age: 5.0–15.0 years) and 40 age and gender‐matched typically developing (TD) children underwent magnetic resonance imaging including a susceptibility‐weighted imaging (SWI) sequence 2–8 weeks post‐injury (M = 39.25, SD = 27.64 days). At 12 and 24‐months post‐ injury, parents completed questionnaires rating their childs social functioning, and environmental factors including socioeconomic status, caregiver mental health and family functioning. Results revealed that longitudinal recovery profiles differed as a function of injury severity, such that among children with severe TBI, social problems significantly increased from 12‐ to 24‐months post‐injury, and were found to be significantly worse than TD controls and children with mild and moderate TBI. In contrast, children with mild and moderate injuries showed few problems at 12‐months post‐injury and little change over time. Pre‐injury environment and SWI did not significantly contribute to outcome at 24‐months, however concurrent caregiver mental health and family functioning explained a large and significant proportion of variance in these outcomes. Overall, this study shows that longitudinal recovery profiles differ as a function of injury severity, with evidence for late‐emerging social problems among children with severe TBI. Poorer long‐term social outcomes were associated with family dysfunction and poorer caregiver mental health at 24‐months post injury, suggesting that efforts to optimize the childs environment and bolster family coping resources may enhance recovery of social problems following pediatric TBI.

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. Hum Brain Mapp 36:1677–1691, 2015.

Social dysfunction after pediatric traumatic brain injury: A translational perspective

Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood and adolescence. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI.

Predictors of longitudinal outcome and recovery of pragmatic language and its relation to externalizing behaviour after pediatric traumatic brain injury

The purpose of the present investigation was to evaluate the contribution of age-at-insult and brain pathology on longitudinal outcome and recovery of pragmatic language in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with mild to severe 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 socio-economic status (SES) to a typically developing (TD) control group (n=43). Participants underwent magnetic resonance imaging (MRI) including a susceptibility weighted imaging (SWI) sequence 2-8 weeks after injury and were assessed on measures of pragmatic language and behavioural functioning at 6- and 24-months after injury. Children and adolescents with TBI of all severity levels demonstrated impairments in these domains at 6-months injury before returning to age-expected levels at 2-years post-TBI. However, while adolescent TBI was associated with post-acute disruption to skills that preceded recovery to age-expected levels by 2-years post injury, the middle childhood TBI group demonstrated impairments at 6-months post-injury that were maintained at 2-year follow up. Reduced pragmatic communication was associated with frontal, temporal and corpus callosum lesions, as well as more frequent externalizing behaviour at 24-months post injury. Findings show that persisting pragmatic language impairment after pediatric TBI is related to younger age at brain insult, as well as microhemorrhagic pathology in brain regions that contribute to the anatomically distributed social brain network. Relationships between reduced pragmatic communication and more frequent externalizing behavior underscore the need for context-sensitive rehabilitation programs that aim to increase interpersonal effectiveness and reduce risk for maladaptive behavior trajectories into the long-term post injury.

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.

Recovery of White Matter following Pediatric Traumatic Brain Injury Depends on Injury Severity

Previous studies in pediatric traumatic brain injury (TBI) have been variable in describing the effects of injury severity on white-matter development. The present study used diffusion tensor imaging to investigate prospective sub-acute and longitudinal relationships between early clinical indicators of injury severity, diffusion metrics, and neuropsychological outcomes. Pediatric patients with TBI underwent magnetic resonance imaging (MRI) (n = 78, mean [M] = 10.56, standard deviation [SD] = 2.21 years) at the sub-acute stage after injury (M = 5.55, SD = 3.05 weeks), and typically developing children were also included and imaged (n = 30, M = 10.60, SD = 2.88 years). A sub-set of the patients with TBI (n = 15) was followed up with MRI 2 years post-injury. Diffusion MRI images were acquired at sub-acute and 2-year follow-up time points and analyzed using Tract-Based Spatial Statistics. At the sub-acute stage, mean diffusivity and axial diffusivity were significantly higher in the TBI group compared with matched controls (p < 0.05). TBI severity significantly predicted diffusion profiles at the sub-acute and 2-year post-injury MRI. Patients with more severe TBI also exhibited poorer information processing speed at 6-months post-injury, which in turn correlated with their diffusion metrics. These findings highlight that the severity of the injury not only has an impact on white-matter microstructure, it also impacts its recovery over time. Moreover, findings suggest that sub-acute microstructural changes may represent a useful prognostic marker to identify children at elevated risk for longer term deficits.

Uncovering the neuroanatomical correlates of cognitive, affective and conative theory of mind in paediatric traumatic brain injury: a neural systems perspective

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

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study

BACKGROUND Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. METHODS The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. RESULTS Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. CONCLUSIONS Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

Social Competence at Two Years after Childhood Traumatic Brain Injury.

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