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

Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d  = 0.44), cognitive fatigue (Cohen d  = 0.59), sleep/rest fatigue (Cohen d  = 0.37), and total fatigue (Cohen d  = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.

Although childhood traumatic brain injury (TBI) has been linked to heightened risk of impaired social skills and behavior, current evidence is weakened by small studies of variable methodological quality. To address these weaknesses, this international multi-cohort study involved synthesis of data from two large observational cohort studies of complicated mild-severe child TBI in Australia and North America. Both studies adopted a unified approach to data collection and coding procedures, providing the opportunity to merge datasets from multiple, well-characterized cohorts for which gold standard measures of social outcomes were collected during the chronic recovery phase. The study involved 218 children, including 33 children with severe TBI, 83 children with complicated mild-moderate TBI, 59 children with orthopedic injury, and 43 age- and sex-matched typically developing control children. All injured children were recruited from academic children's hospitals and underwent direct cognitive assessments including measures of theory of mind (ToM) at least 1-year post- injury. Parents rated their child's social adjustment using standardized measures of social skills, communication and behavior. Results showed a brain-injury specific effect on ToM abilities, such that children with both complicated mild to moderate and severe TBI displayed significantly poorer ToM than children without TBI. In mediator models, poorer ToM predicted poorer parent-rated self-direction and social skills, as well as more frequent behavioral symptoms. The ToM mediated the effect of severe TBI on parent ratings of communication and social skills, as well as on overall behavior symptoms. The findings suggest that deficits in ToM are evident across the spectrum of TBI severity and represent one mechanism linking severe child TBI to long-term social adjustment difficulties. The findings underscore the value of large-scale data harmonization projects to increase the quality of evidence regarding the outcomes of TBI. Clinical and scientific implications are discussed.

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

Social dysfunction is a common and disabling outcome of childhood traumatic brain injury (TBI); however, the mechanisms that link early brain injury to impaired social behavior are unclear. This longitudinal prospective study involved 129 children, including 86 children with TBI (53 mild, 33 moderate-severe TBI) and 43 age-matched typically developing control (TDC) children. Children with TBI were recruited via consecutive admissions to the emergency department of the Royal Children's Hospital, Melbourne Australia. At 6 months post-injury, all participants were assessed on measures of intellectual functioning, and parents provided ratings of children's self-regulation skills using gold standard measures of everyday executive function. At 12-month follow up, parents rated children's social adjustment using standardized measures of social skills, communication, and behavior. As expected, children with moderate-severe TBI were rated by parents as having greater self-regulation problems, worse social skills, and poorer communication than the mild TBI and TDC groups. In mediation models, greater self-regulation problems at 6 months post-injury were predictive of poorer social skills and worse overall social adjustment at 12-month follow-up. Moreover, self-regulation skills mediated the effect of moderate-severe TBI, but not mild TBI, on social skills and overall social adjustment. Our findings show that, while impaired social adjustment is common at 12 months following moderate-severe child TBI, the impact of TBI on these outcomes is likely mediated by its effect on self-regulation skills. Evidence for robust prospective associations between self-regulation deficits and later social adjustment difficulties have implications for early identification of children at high risk for chronic social problems.

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.

Emotion perception (EP) forms an integral part of social communication and is critical to attain developmentally appropriate goals. This skill, which emerges relatively early in development, is driven by increasing connectivity among regions of a distributed sociocognitive neural network and may be vulnerable to disruption from early-childhood traumatic brain injury (TBI). The present study aimed to evaluate the very-long-term effect of childhood TBI on EP, as well as examine the contribution of injury- and non-injury-related risk and resilience factors to variability in sociocognitive outcomes. Thirty-four young adult survivors of early-childhood TBI (mean [M], 20.62 years; M time since injury, 16.55 years) and 16 typically developing controls matched for age, gender, and socioeconomic status were assessed using tasks that required recognition and interpretation of facial and prosodic emotional cues. Survivors of severe childhood TBI were found to have significantly poorer emotion perception than controls and young adults with mild-to-moderate injuries. Further, poorer emotion perception was associated with reduced volume of the posterior corpus callosum, presence of frontal pathology, lower SES, and a less-intimate family environment. Our findings lend support to the vulnerability of the immature "social brain" network to early disruption and underscore the need for context-sensitive rehabilitation that optimizes early family environments to enhance recovery of EP skills after childhood TBI.