Linda Ewing-Cobbs

Objective: To evaluate the effect of child and family factors on children's participation outcomes 2 to 3 years following traumatic brain injury (TBI). Setting: Two level 1 pediatric trauma centers. Participants: Children aged 0 to 15 years with TBI at all severity levels or an orthopedic injury. Design: Prospective cohort. Main Measures: Caregivers completed the Child and Adolescent Scale of Participation (CASP) at 2- and 3-year follow-ups. The CASP was categorized as more than 90 or 90 or less on a 100-point scale, with 90 or less representing the 10th percentile and below in this sample. Modified Poisson regression models were used to describe relative risk of the CASP at 90 or less at 2 to 3 years postinjury, adjusting for preinjury family environment variables and injury group. A secondary analysis only included children who were 31 months or older at injury (n = 441) to determine whether changes in functional outcome (Pediatric Injury Functional Outcome Scale, PIFOS) and executive functions (Behavior Rating Inventory of Executive Function, BRIEF) from preinjury to 1 year after injury predicted CASP scores at the 2- or 3-year follow-up. Results: Seventy-eight percent (596/769) of children who had a completed preinjury survey had a completed CASP. In the adjusted model, children with severe TBI had a nearly 3 times higher risk (RR = 2.90; 95% CI, 1.43-5.87) of reduced participation than children with an orthopedic injury. In the secondary analysis, lower functional skills (5-point increase in 1-year postinjury PIFOS score) (RR = 1.36; 95% CI, 1.18-1.57) and less favorable family function (RR = 1.46; 95% CI, 1.02-2.10) were associated with reduced participation in both girls and boys. Conclusion: Participation in home, school, and community activities after TBI is related to multiple biopsychosocial factors. Participation-focused interventions are needed to reduce barriers to involvement and assist children and families to close the participation gap across settings.

Traumatic injury is linked increasingly to alterations in both stress response systems and psychological health. We investigated reactivity of salivary analytes of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (salivary alpha amylase, sAA) during a psychosocial stress procedure in relation to psychological health outcomes. In a prospective cohort design, stress reactivity of children ages 8 to 15 years hospitalized for traumatic brain injury (TBI; n = 74) or extracranial injury (EI; n = 35) was compared with healthy controls ( n = 51) 7 months after injury. Area under the curve increase (AUCinc) assessed pre-stressor to post-stressor cortisol and sAA values. Multi-variable general linear models evaluated demographic, family functioning, group, cortisol, and sAA AUCinc, and their interactions in relation to concurrent child and parent ratings of emotion regulation and internalizing and externalizing problems. Although AUCinc values were similar across groups, their relations with outcomes varied by group. Higher stress reactivity is typically associated with fewer adjustment problems. Relative to controls, greater sAA reactivity was associated with greater emotion dysregulation after TBI. In contrast, the relation of sAA reactivity with internalizing and generalized anxiety scores was flatter for both TBI and EI groups. The flattened and/or reversed direction of sAA reactivity with psychological health outcomes after TBI, and to a lesser degree EI, suggests autonomic nervous system dysregulation. Across groups, sAA reactivity interacted with sex on several psychological health outcomes with greater dysregulation in girls than in boys. Our findings highlight altered sAA, but not cortisol reactivity, as a potential mechanism of biological vulnerability associated with poorer adjustment after TBI.

Following pediatric traumatic brain injury (TBI), post-concussion symptoms (PCS) and post-traumatic stress symptoms (PTSS) occur commonly; however, it is unknown to what degree they overlap. The study examined PCS and PTSS persisting 7 weeks after injury in children and adolescents ages 8-15 years with TBI ( n = 89) or extracranial injury (EI; n = 40) after vehicle collisions. TBI was divided into mild, complicated-mild/moderate, and severe groups. Parents retrospectively rated children's pre-injury symptoms and behavior problems, and children completed self-report measures after injury. PCS and PTSS total scores were significantly correlated in TBI and EI groups, respectively, for child ( r _s = 0.75; r _s = 0.44), and adolescent ( r _s = 0.61; r _s = 0.67) cohorts. Generalized linear models examined whether injury type and severity, age, sex, and pre-injury symptom ratings predicted PCS and PTSS total scores and factor scores. Specific PCS and PTSS factor scores were elevated in different TBI severity groups, with most frequent problems following mild or severe TBI. PCS did not differ by age; however, girls had more emotional symptoms than boys. Only PTSS were predicted by pre-injury externalizing behavior. Significant age by sex interactions indicated that adolescent girls had more total, avoidance, and hyperarousal PTSS symptoms than younger girls or all boys. PCS and PTSS significantly overlapped in both TBI and EI groups, highlighting shared persistent symptoms after injury. Shared vulnerability factors included female sex, milder TBI, and poorer pre-injury adjustment. Older age was a unique vulnerability factor for PTSS. Psychological health interventions after injury should be customized to address comorbid symptoms.

Objective: To model pre-injury child and family factors associated with the trajectory of internalizing and externalizing behavior problems across the first 3 years in children with pediatric traumatic brain injury (TBI) relative to children with orthopedic injuries (OI). Parent-reported emotional symptoms and conduct problems were expected to have unique and shared predictors. We hypothesized that TBI, female sex, greater pre-injury executive dysfunction, adjustment problems, lower income, and family dysfunction would be associated with less favorable outcomes.Methods: In a prospective longitudinal cohort study, we examined the level of behavior problems at 12 months after injury and rate of change from pre-injury to 12 months and from 12 to 36 months in children ages 4–15 years with mild to severe TBI relative to children with OI. A structural equation model framework incorporated injury characteristics, child demographic variables, as well as pre-injury child reserve and family attributes. Internalizing and externalizing behavior problems were indexed using the parent-rated Emotional Symptoms and Conduct Problems scales from the Strengths and Difficulties questionnaire.Results: The analysis cohort of 534 children [64% boys, M (SD) 8.8 (4.3) years of age] included 395 with mild to severe TBI and 139 with OI. Behavior ratings were higher after TBI than OI but did not differ by TBI severity. TBI, higher pre-injury executive dysfunction, and lower income predicted the level and trajectory of both Emotional Symptoms and Conduct Problems at 12 months. Female sex and poorer family functioning were vulnerability factors associated with greater increase and change in Emotional Symptoms by 12 months after injury; unique predictors of Conduct Problems included younger age and prior emotional/behavioral problems. Across the long-term follow-up from 12 to 36 months, Emotional Symptoms increased significantly and Conduct Problems stabilized. TBI was not a significant predictor of change during the chronic stage of recovery.Conclusions: After TBI, Emotional Symptoms and Conduct Problem scores were elevated, had different trajectories of change, increased or stayed elevated from 12 to 36 months after TBI, and did not return to pre-injury levels across the 3 year follow-up. These findings highlight the importance of addressing behavioral problems after TBI across an extended time frame.

Traumatic brain injury (TBI) produces microstructural damage to white matter pathways connecting neural structures in pre-frontal and striatal regions involved in self-regulation (SR). Dorsal and ventral frontostriatal pathways have been linked to cognitive (“cool”) and emotional (“hot”) SR, respectively. We evaluated the relation of frontostriatal pathway fractional anisotropy (FA) 2 months post-TBI on cool and hot SR assessed 7 months post-TBI. Participants were 8–15 years of age, including children with uncomplicated mild TBI (mTBI; n = 24), more severe TBI (complicated-mild, moderate, severe [cms]TBI; n = 60), and typically developing (TD) children ( n = 55). Diffusion tensor tractography was used to map frontostriatal pathways. Cool SR included focused and sustained attention performance, and parent-reported attention, whereas hot SR included risk-taking performance and parent-reported emotional control. Multivariate general linear models showed that children with cmsTBI had greater parent-reported cool and hot SR difficulties and lower dorsal and ventral FA than TD children. Focused attention, risk taking, and emotional control correlated with FA of specific dorsal and ventral pathways; however, only the effect of TBI on focused attention was mediated by integrity of dorsal pathways. Results suggest that frontostriatal FA may serve as a biomarker of risk for SR difficulties or to assess response to interventions targeting SR in pediatric TBI and in broader neurodevelopmental populations.

This study investigated patterns of cortical organization in adolescents who had sustained a traumatic brain injury (TBI) during early childhood to determine ways in which early head injury may alter typical brain development. Increased gyrification in other patient populations is associated with polymicrogyria and aberrant development, but this has not been investigated in TBI. Seventeen adolescents (mean age = 14.1 ± 2.4) who sustained a TBI between 1–8 years of age, and 17 demographically-matched typically developing children (TDC) underwent a high-resolution, T1-weighted 3-Tesla magnetic resonance imaging (MRI) at 6–15 years post-injury. Cortical white matter volume and organization was measured using FreeSurfer's Local Gyrification Index (LGI). Despite a lack of significant difference in white matter volume, participants with TBI demonstrated significantly increased LGI in several cortical regions that are among those latest to mature in normal development, including left parietal association areas, bilateral dorsolateral and medial frontal areas, and the right posterior temporal gyrus, relative to the TDC group. Additionally, there was no evidence of increased surface area in the regions that demonstrated increased LGI. Higher Vineland-II Socialization scores were associated with decreased LGI in right frontal and temporal regions. The present results suggest an altered pattern of expected development in cortical gyrification in the TBI group, with changes in late-developing frontal and parietal association areas. Such changes in brain structure may underlie cognitive and behavioral deficits associated with pediatric TBI. Alternatively, increased gyrification following TBI may represent a compensatory mechanism that allows for typical development of cortical surface area, despite reduced brain volume.

Annually, approximately 3 million children around the world experience traumatic brain injuries (TBIs), of which up to 20% are characterized as moderate to severe (msTBI) and/or have abnormal imaging findings. Affected children are vulnerable to long-term cognitive and behavioral dysfunction, as injury can disrupt or alter ongoing brain maturation. Post-injury outcomes are highly variable, and there is only limited understanding of how inter-individual differences in outcomes arise. Small sample sizes have also complicated efforts to better understand factors influencing the impact of TBI on the developing brain. White matter (WM) disruption is a critical aspect of TBI neuropathology and diffusion MRI (dMRI) is particularly sensitive to microstructural abnormalities. Here we present the results of a coordinated analysis of dMRI data across ten cohorts from three countries. We had three primary aims: (1) to characterize the nature and extent of WM disruption across key post-injury intervals (acute/subacute - within 2 months, post-acute - 2-6 months, chronic - 6+ months); (2) evaluate the impact of age and sex on WM in the context of injury; and (3) to examine associations between WM and neurobehavioral outcomes. Based on data from 507 children and adolescents (244 with complicated mild to severe TBI and 263 control children), we report widespread WM disruption across all post-injury intervals. As expected, injury severity was a significant contributor to the pattern and extent of WM degradation, but explained less variance in dMRI measures with increasing time since injury, supporting other research indicating that other factors contribute increasingly to outcomes over time. The corpus callosum appears to be particularly vulnerable to injury, an effect that persists years post-TBI. We also report sex differences in the effect of TBI on the uncinate fasciculus (UNC), a structure with a key role in emotion regulation. Females with a TBI had significantly lower fractional anisotropy (FA) in the UNC than those with no TBI, and this phenomenon was further associated with more frequent parent-reported behavioral problems as measured by the Child Behavior Checklist (CBCL). These effects were not detected in males. With future harmonization of imaging and neurocognitive data, more complex modeling of factors influencing outcomes will be possible and help to identify clinically-meaningful patient subtypes.

Pre-frontal limbic circuitry is vulnerable to effects of stress and injury. We examined microstructure of pre-frontal limbic circuitry after traumatic brain injury (TBI) or extracranial injury (EI) and its relation to post-traumatic stress symptoms (PTSS). Participants aged 8 to 15 years who sustained mild to severe TBI ( n = 53) or EI ( n = 26) in motor vehicle incidents were compared with healthy children ( n = 38) in a prospective longitudinal study. At the seven-week follow-up, diffusion tensor imaging was obtained in all groups; injured children completed PTSS ratings using a validated scale. Using probabilistic diffusion tensor tractography, pathways were seeded from bilateral amygdalae and hippocampi to estimate the trajectory of white matter connecting them to each other and to targeted pre-frontal cortical (PFC) regions. Microstructure was estimated using fractional anisotropy (FA) in white matter and mean diffusivity (MD) in gray matter. Pre-frontal limbic microstructure was similar across groups, except for reduced FA in the right hippocampus to orbital PFC pathway in the injured versus healthy group. We examined microstructure of components of pre-frontal limbic circuitry with concurrently obtained PTSS cluster scores in the injured children. Neither microstructure nor PTSS scores differed significantly in the TBI and EI groups. Across PTSS factors, specific symptom clusters were related positively to higher FA and MD. Higher hyperarousal, avoidance, and re-experiencing symptoms were associated with higher FA in amygdala to pre-frontal and hippocampus to amygdala pathways. Higher hippocampal MD had a central role in hyperarousal and emotional numbing symptoms. Age moderated the relation of white and gray matter microstructure with hyperarousal scores. Our findings are consistent with models of traumatic stress that implicate disrupted top-down PFC and hippocampal moderation of overreactive subcortical threat arousal systems. Alterations in limbic pre-frontal circuitry and PTSS place children with either brain or body injuries at elevated risk for both current and future psychological health problems.

OBJECTIVES: We examined whether preinjury, demographic, and family factors influenced vulnerability to postconcussion symptoms (PCSs) persisting the year after mild traumatic brain injury (mTBI). METHODS: Children with mTBI (n = 119), complicated mild traumatic brain injury (cmTBI) (n = 110), or orthopedic injury (OI) (n = 118), recruited from emergency departments, were enrolled in a prospective, longitudinal cohort study. Caregivers completed retrospective surveys to characterize preinjury demographic, child, and family characteristics. PCSs were assessed using a validated rating scale. With multivariable general linear models adjusted for preinjury symptoms, we examined predictors of PCSs 3, 6, and 12 months after injury in children ages 4 to 8, 9 to 12, and 13 to 15 years at injury. With logistic regression, we examined predictors of chronic PCSs 1 year after traumatic brain injury. RESULTS: Postinjury somatic, emotional, cognitive, and fatigue PCSs were similar in the mTBI and cmTBI groups and significantly elevated compared with the OI group. PCS trajectories varied with age and sex. Adolescents had elevated PCSs that improved; young children had lower initial symptoms and less change. Despite similar preinjury PCSs, girls had elevated symptoms across all time points compared with boys. PCS vulnerability factors included female sex, adolescence, preinjury mood problems, lower income, and family discord. Social capital was a protective factor. PCSs persisted in 25% to 31% of the traumatic brain injury group and 18% of the OI group at 1 year postinjury. The odds of chronic PCSs were almost twice as high in girls as in boys and were >4 times higher in young children with cmTBI than in those with mTBI. CONCLUSIONS: A significant minority of children with mTBI and OI have PCSs that persisted 1 year after injury.

This prospective longitudinal study investigated sleep disturbance (SD) and internalizing problems after traumatic injury, including traumatic brain injury (TBI) or extracranial/bodily injury (EI) in children and adolescents, relative to typically developing (TD) children. We also examined longitudinal relations between SD and internalizing problems postinjury. Participants (N = 87) ages 8-15 included youth with TBI, EI, and TD children. Injury groups were recruited from a Level 1 trauma center after sustaining vehicle-related injuries. Parent-reported SD and internalizing problems were assessed at preinjury/baseline, and 6 and 12 months postinjury. Linear mixed models evaluated the relation of group and time of assessment on outcomes. Controlling for age, the combined traumatic injury group experienced significantly higher postinjury levels of SD (p = .042) and internalizing problems (p = .024) than TD children; however, TBI and EI injury groups did not differ from each other. Injury severity was positively associated with SD in the EI group only, but in both groups SD was associated with additional postinjury sequelae, including fatigue and externalizing behavior problems. Internalizing problems predicted subsequent development of SD but not vice versa. The relation between injury and SD 1 year later was consistent with mediation by internalizing problems at 6 months postinjury. Children with both types of traumatic injury demonstrated higher SD and internalizing problems than healthy children. Internalizing problems occurring either prior to or following pediatric injury may be a risk factor for posttraumatic SD. Consequently, internalizing problems may be a promising target of intervention to improve both SD and related adjustment concerns. (PsycINFO Database Record