Stress Reactivity After Pediatric Traumatic Brain Injury: Relation With Behavioral Adjustment.

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.

Post-Traumatic Stress Symptoms after Pediatric Injury: Relation to Pre-Frontal Limbic Circuitry.

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.

Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms.

Injury is the leading cause of death and disability in childhood. Injured children are at high risk for developing alterations in stress response systems and post-traumatic stress symptoms (PTSS) that may compromise long-term physical and psychological health. In a prospective, observational cohort study, we examined individual differences in, and correlates of, stress-reactivity of the hypothalamic-pituitary-adrenal axis (HPA; salivary cortisol) and autonomic nervous system (ANS; salivary alpha amylase, sAA) following pediatric injury. Participants were 8-15 years of age and hospitalized for traumatic brain injury (TBI; n=55; M age=13.9 yrs; 40 males) or extracranial injury (EI; n=29; M age 12.3 yrs, 20 males) following vehicular accidents. Six months post-injury, saliva was collected before and after the Trier Social Stress Test and later assayed for cortisol and sAA. Relative to a healthy non-injured comparison group (n=33; M age=12.5 yrs, 16 males), injured children (ages 8-12 years), but not adolescents (ages 13-15 yrs), had higher cortisol levels; regardless of age, injured participants showed dampened cortisol reactivity to social evaluative threat. Compared to participants with EI, children with TBI had elevated cortisol and adolescents had elevated sAA. With respect to PTSS, individual differences in sAA were negatively correlated with avoidance in the TBI group and positively correlated with emotional numbing within the EI group. Importantly, psychological and neurobiological sequelae were weakly related to injury severity. Given the high prevalence of pediatric injury, these sequelae affect many children and represent a significant public health concern. Consequently, surveillance of post-traumatic sequelae should include the full spectrum of injury severity. Monitoring the activity, reactivity, and regulation of biological systems sensitive to environmental insults may advance our understanding of individual differences in sequelae and adaptation following traumatic pediatric injury.

Comparing treatments for children with ADHD and word reading difficulties: A randomized clinical trial.

OBJECTIVE: This trial compared attention-deficit/hyperactivity disorder (ADHD) treatment alone, intensive reading intervention alone, and their combination for children with ADHD and word reading difficulties and disabilities (RD). METHOD: Children (n = 216; predominantly African American males) in Grades 2-5 with ADHD and word reading/decoding deficits were randomized to ADHD treatment (medication + parent training), reading treatment (reading instruction), or combined ADHD + reading treatment. Outcomes were parent and teacher ADHD ratings and measures of word reading/decoding. Analyses utilized a mixed models covariate-adjusted gain score approach with posttest regressed onto pretest. RESULTS: Inattention and hyperactivity/impulsivity outcomes were significantly better in the ADHD (parent Hedges's g = .87/.75; teacher g = .67/.50) and combined (parent g = 1.06/.95; teacher g = .36/41) treatment groups than reading treatment alone; the ADHD and Combined groups did not differ significantly (parent g = .19/.20; teacher g = .31/.09). Word reading and decoding outcomes were significantly better in the reading (word reading g = .23; decoding g = .39) and combined (word reading g = .32; decoding g = .39) treatment groups than ADHD treatment alone; reading and combined groups did not differ (word reading g = .09; decoding g = .00). Significant group differences were maintained at the 3- to 5-month follow-up on all outcomes except word reading. CONCLUSIONS: Children with ADHD and RD benefit from specific treatment of each disorder. ADHD treatment is associated with more improvement in ADHD symptoms than RD treatment, and reading instruction is associated with better word reading and decoding outcomes than ADHD treatment. The additive value of combining treatments was not significant within disorder, but the combination allows treating both disorders simultaneously. (PsycINFO Database Record

Long-Term School Outcomes of Children and Adolescents With Traumatic Brain Injury.

OBJECTIVE: To better understand the impact of age at injury, severity of injury, and time since injury on long-term school outcomes of children with traumatic brain injury (TBI). PARTICIPANTS: Four groups of children: complicated mild/moderate TBI (n = 23), severe TBI (n = 56), orthopedic injury (n = 35), and healthy controls (n = 42). Children with TBI were either 2 years postinjury or 6 years postinjury. DESIGN: Cross-sectional design. MEASURES: School records as well as parental ratings of functional academic skills and school competency. RESULTS: Children with severe TBI had consistently high usage of school services and low school competency ratings than children with orthopedic injuries and healthy controls. In contrast, children with complicated-mild/moderate TBI were significantly more likely to receive school support services and have lower competence ratings at 6 years than at 2 years postinjury. Students injured at younger ages had lower functional academic skill ratings than those injured at older ages. CONCLUSIONS: These findings highlight the increasing academic challenges faced over time by students with complicated-mild/moderate TBI and the vulnerability of younger children to poorer development of functional academic skills.

Assessing recovery and disability after physical trauma: the Pediatric Injury Functional Outcome Scale.

OBJECTIVE: To establish reliability and validity of the Pediatric Injury Functional Outcome Scale (PIFOS), a brief injury-specific rating scale covering motor, self-care, communication, social-emotional, cognition, physical, and academic areas. METHODS: In a prospective longitudinal study, the PIFOS structured interview was administered to parents of children 3-15 years of age at 3 and 12 months after hospitalization for traumatic brain injury (TBI) or orthopedic injury (OI). RESULTS: The total score had good internal consistency (α = .90-.93) and inter-rater reliability (α = .90) and correlated significantly with injury severity and neurodevelopmental outcomes. Generalized linear modeling showed the PIFOS was sensitive to the type and severity of injury, showed specific initial and persisting difficulties following TBI and OI, and was responsive to change during the first year after injury. Both groups had residual difficulties with coordination, emotionality, social participation, and discomfort. CONCLUSION: The PIFOS is useful in examining recovery in natural history and intervention studies.

Social interaction in young children with inflicted and accidental traumatic brain injury: relations with family resources and social outcomes.

Core social interaction behaviors were examined in young children 0-36 months of age who were hospitalized for accidental (n = 61) or inflicted (n = 64) traumatic brain injury (TBI) in comparison to typically developing children (n = 60). Responding to and initiating gaze and joint attention (JA) were evaluated during a semi-structured sequence of social interactions between the child and an examiner at 2 and 12 months after injury. The accidental TBI group established gaze less often and had an initial deficit initiating JA that resolved by the follow-up. Contrary to expectation, children with inflicted TBI did not have lower rates of social engagement than other groups. Responding to JA was more strongly related than initiating JA to measures of injury severity and to later cognitive and social outcomes. Compared to complicated-mild/moderate TBI, severe TBI in young children was associated with less responsiveness in social interactions and less favorable caregiver ratings of communication and social behavior. JA response, family resources, and group interacted to predict outcomes. Children with inflicted TBI who were less socially responsive and had lower levels of family resources had the least favorable outcomes. Low social responsiveness after TBI may be an early marker for later cognitive and adaptive behavior difficulties.

Recommendations for the use of common outcome measures in pediatric traumatic brain injury research.

This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.

Social communication in young children with traumatic brain injury: relations with corpus callosum morphometry.

The purpose of the present investigation was to characterize the relations of specific social communication behaviors, including joint attention, gestures, and verbalization, with surface area of midsagittal corpus callosum (CC) subregions in children who sustained traumatic brain injury (TBI) before 7 years of age. Participants sustained mild (n=10) or moderate-severe (n=26) noninflicted TBI. The mean age at injury was 33.6 months; mean age at MRI was 44.4 months. The CC was divided into seven subregions. Relative to young children with mild TBI, those with moderate-severe TBI had smaller surface area of the isthmus. A semi-structured sequence of social interactions between the child and an examiner was videotaped and coded for specific social initiation and response behaviors. Social responses were similar across severity groups. Even though the complexity of their language was similar, children with moderate-severe TBI used more gestures than those with mild TBI to initiate social overtures; this may indicate a developmental lag or deficit as the use of gestural communication typically diminishes after age 2. After controlling for age at scan and for total brain volume, the correlation of social interaction response and initiation scores with the midsagittal surface area of the CC regions was examined. For the total group, responding to a social overture using joint attention was significantly and positively correlated with surface area of all regions, except the rostrum. Initiating joint attention was specifically and negatively correlated with surface area of the anterior midbody. Use of gestures to initiate a social interaction correlated significantly and positively with surface area of the anterior and posterior midbody. Social response and initiation behaviors were selectively related to regional callosal surface areas in young children with TBI. Specific brainbehavior relations indicate early regional specialization of anterior and posterior CC for social communication.

Mean diffusivity in the amygdala correlates with anxiety in pediatric TBI.

Traumatic brain injury (TBI) and orthopedic injury (OI) patients are prone to anxiety and mood disorders. In the present study, we integrated anatomical and diffusion tensor neuroimaging to investigate structural properties of the amygdala and hippocampus, gray matter regions implicated in anxiety and mood disorders. Children and adolescents were evaluated during the late sub-acute phase of recovery following trauma resulting from either moderate to severe TBI or OI. Mean diffusivity (MD) of the amygdala and hippocampus was elevated following TBI. An interaction of hemisphere, structure, and group revealed that MD of the right amygdala was elevated in females with TBI. Self-reported anxiety scores were not related to either volume or microstructure of the hippocampus, or to volume or fractional anisotropy of the amygdala. Left amygdala MD in the TBI group accounted for 17.5% of variance in anxiety scores. Anxiety symptoms may be mediated by different mechanisms in patients with TBI or OI.

Predicting behavioral deficits in pediatric traumatic brain injury through uncinate fasciculus integrity.

Behavioral dysregulation is a common and detrimental consequence of traumatic brain injury (TBI) in children that contributes to poor academic achievement and deficits in social development. Unfortunately, behavioral dysregulation is difficult to predict from either injury severity or early neuropsychological evaluation. The uncinate fasciculus (UF) connects orbitofrontal and anterior temporal lobes, which are commonly implicated in emotional and behavioral regulation. Using probabilistic diffusion tensor tractography (DTT), we examined the relationship between the integrity of the UF 3 months post-injury and ratings of executive functions 12 months post-injury in children with moderate to severe TBI and a comparison group with orthopedic injuries. As expected, fractional anisotropy of the UF was lower in the TBI group relative to the orthopedic injury group. DTT metrics from the UF served as a biomarker and predicted ratings of emotional and behavior regulation, but not metacognition. In contrast, the Glasgow Coma Scale score was not related to either UF integrity or to executive function outcomes. Neuroanatomical biomarkers like the uncinate fasciculus may allow for early identification of behavioral problems and allow for investigation into the relationship of frontotemporal networks to brain-behavior relationships.

Arrested development and disrupted callosal microstructure following pediatric traumatic brain injury: relation to neurobehavioral outcomes.

Chronic pediatric traumatic brain injury (TBI) is associated with significant and persistent neurobehavioral deficits. Using diffusion tensor imaging (DTI), we examined area, fractional anisotropy (FA), radial diffusion, and axial diffusion from six regions of the corpus callosum (CC) in 41 children and adolescents with TBI and 31 comparison children. Midsagittal cross-sectional area of the posterior body and isthmus was similar in younger children irrespective of injury status; however, increased area was evident in the older comparison children but was obviated in older children with TBI, suggesting arrested development. Similarly, age was correlated significantly with indices of tissue microstructure only for the comparison group. TBI was associated with significant reduction in FA and increased radial diffusivity in the posterior third of the CC and in the genu. The axial diffusivity did not differ by either age or group. Logistic regression analyses revealed that FA and radial diffusivity were equally sensitive to post-traumatic changes in 4 of 6 callosal regions; radial diffusivity was more sensitive for the rostral midbody and splenium. IQ, working memory, motor, and academic skills were correlated significantly with radial diffusion and/or FA from the isthmus and splenium only in the TBI group. Reduced size and microstructural changes in posterior callosal regions after TBI suggest arrested development, decreased organization, and disrupted myelination. Increased radial diffusivity was the most sensitive DTI-based surrogate marker of the extent of neuronal damage following TBI; FA was most strongly correlated with neuropsychological outcomes.

Late intellectual and academic outcomes following traumatic brain injury sustained during early childhood.

OBJECT: Although long-term neurological outcomes after traumatic brain injury (TBI) sustained early in life are generally unfavorable, the effect of TBI on the development of academic competencies is unknown. The present study characterizes intelligence quotient (IQ) and academic outcomes an average of 5.7 years after injury in children who sustained moderate to severe TBI prior to 6 years of age. METHODS: Twenty-three children who suffered inflicted or noninflicted TBI between the ages of 4 and 71 months were enrolled in a prospective, longitudinal cohort study. Their mean age at injury was 21 months; their mean age at assessment was 89 months. The authors used general linear modeling approaches to compare IQ and standardized academic achievement test scores from the TBI group and a community comparison group (21 children). Children who sustained early TBI scored significantly lower than children in the comparison group on intelligence tests and in the reading, mathematical, and language domains of achievement tests. Forty-eight percent of the TBI group had IQs below the 10th percentile. During the approximately 5-year follow-up period, longitudinal IQ testing revealed continuing deficits and no recovery of function. Both IQ and academic achievement test scores were significantly related to the number of intracranial lesions and the lowest postresuscitation Glasgow Coma Scale score but not to age at the time of injury. Nearly 50% of the TBI group failed a school grade and/or required placement in self-contained special education classrooms; the odds of unfavorable academic performance were 18 times higher for the TBI group than the comparison group. CONCLUSIONS: Traumatic brain injury sustained early in life has significant and persistent consequences for the development of intellectual and academic functions and deleterious effects on academic performance.

Executive functions following traumatic brain injury in young children: a preliminary analysis.

To examine executive processes in young children with traumatic brain injury (TBI), we evaluated performance of 44 children who sustained moderate-to-severe TBI prior to age 6 and to 39 comparison children on delayed response (DR), stationary boxes, and spatial reversal (SR) tasks. The tasks have different requirements for holding mental representations in working memory (WM) over a delay, inhibiting prepotent responses, and shifting response set. Age at the time of testing was divided into 10- to 35- and 36- to 85-month ranges. In relation to the community comparison group, children with moderate-to-severe TBI scored significantly lower on indexes of WM/inhibitory control (IC) on DR and stationary boxes tasks. On the latter task, the Age x Group interaction indicated that performance efficiency was significantly reduced in the older children with TBI relative to the older comparison group; performance was similar in younger children irrespective of injury status. The TBI and comparison groups did not differ on the SR task, suggesting that shifting response set was not significantly altered by TBI. In both the TBI and comparison groups, performance improved with age on the DR and stationary boxes tasks. Age at testing was not significantly related to scores on the SR task. The rate of acquisition of working memory (WM) and IC increases steeply during preschool years, but the abilities involved in shifting response set show less increase across age groups (Espy, Kaufmann, & Glisky, 2001; Luciana & Nelson, 1998). The findings of our study are consistent with the rapid development hypothesis, which predicts that skills in a rapid stage of development will be vulnerable to disruption by brain injury.

Predictors of outcome following traumatic brain injury in young children.

The relationship between clinical and neuroimaging variables and multiple outcome measures was examined in a longitudinal, prospective study of 60 children less than 6 years of age who sustained either inflicted or noninflicted traumatic brain injury. Hierarchical multiple regression indicated that the modified Glasgow Coma Scale score, the duration of impaired consciousness and the number of intracranial lesions visualized on CT/MRI accounted for a significant amount of the variance in the Glasgow Outcome Scale (GOS), cognitive and motor scores at baseline, 3- and 12-month evaluations. Inflicted brain injury adversely affected both GOS and cognitive outcomes. Pupillary abnormalities were associated with poorer motor outcome. Neither age at injury nor the Injury Severity Score accounted for significant variability in outcomes.