Role of Neurocognitive Factors in Academic Fluency for Children and Adults With Spina Bifida Myelomeningocele.

OBJECTIVES: Fluency is a major problem for individuals with neurodevelopmental disorders, including fluency deficits for academic skills. The aim of this study was to determine neurocognitive predictors of academic fluency within and across domains of reading, writing, and math, in children and adults, with and without spina bifida. In addition to group differences, we expected some neurocognitive predictors (reaction time, inattention) to have similar effects for each academic fluency outcome, and others (dexterity, vocabulary, nonverbal reasoning) to have differential effects across outcomes. METHODS: Neurocognitive predictors were reaction time, inattention, dexterity, vocabulary, and nonverbal reasoning; other factors included group (individuals with spina bifida, n=180; and without, n=81), age, and demographic and untimed academic content skill covariates. Univariate and multivariate regressions evaluated hypotheses. RESULTS: Univariate regressions were significant and robust (R 2 =.78, .70, .73, for reading, writing, and math fluency, respectively), with consistent effects of covariates, age, reaction time, and vocabulary; group and group moderation showed small effect sizes (<2%). Multivariate contrasts showed differential prediction across academic fluency outcomes for reaction time and vocabulary. CONCLUSIONS: The novelty of the present work is determining neurocognitive predictors for an important outcome (academic fluency), within and across fluency domains, across population (spina bifida versus typical), over a large developmental span, in the context of well-known covariates. Results offer insight into similarities and differences regarding prediction of different domains of academic fluency, with implications for addressing academic weakness in spina bifida, and for evaluating similar questions in other neurodevelopmental disorders. (JINS, 2019, 25, 249-265).

Theory of Mind and Parental Nurturance as Predictors of Peer Relationships After Childhood Traumatic Brain Injury: A Test of Moderated Mediation.

OBJECTIVE: Traumatic brain injury (TBI) sustained in childhood is associated with poor social outcomes. This study investigated the role of theory of mind (ToM) as a mediator of the relation between TBI and peer rejection/victimization and reciprocated friendships, as well as the moderating effect of parental nurturance on those relationships. METHOD: Participants were children of 8-13 years old (M = 10.45, SD = 1.47), including 13 with severe TBI, 39 with complicated mild/moderate TBI, and 32 children with orthopedic injuries. Data on peer rejection/victimization and friendship were collected in school classrooms using the Extended Class Play and friendship nominations. Parents rated parental nurturance using the Child-Rearing Practices Report. Finally, ToM was measured based on children's average performance across three tasks measuring different aspects of ToM. RESULTS: Severe TBI was associated with poorer ToM, greater peer rejection/victimization, and fewer reciprocated friendships. ToM mediated the relation between severe TBI and peer rejection/victimization (i.e., severe TBI predicted poorer ToM, which in turn predicted greater rejection/victimization). Parental nurturance significantly moderated this relation, such that the mediating effect of ToM was significant only at low and average levels of parental nurturance, for both severe and complicated mild/moderate TBI groups. Neither the mediating effect of ToM nor the moderating effect of parental nurturance was significant for reciprocated friendships. CONCLUSION: High parental nurturance may mitigate the negative effects of ToM deficits on risk of peer rejection/victimization among children with TBI. Interventions designed to increase parental nurturance or ToM may promote better social outcomes among children with TBI.

Rejection Sensitivity as a Moderator of Psychosocial Outcomes Following Pediatric Traumatic Brain Injury.

OBJECTIVES: The current study examines whether psychosocial outcomes following pediatric traumatic brain injury (TBI) vary as a function of children's rejection sensitivity (RS), defined as their disposition to be hypersensitive to cues of rejection from peers. METHODS: Children ages 8-13 with a history of severe TBI (STBI, n=16), complicated mild/moderate TBI (n=35), or orthopedic injury (OI, n=49) completed measures assessing self-esteem and RS on average 3.28 years post-injury (SD=1.33, range=1.25-6.34). Parents reported on their child's emotional and behavioral functioning and social participation. RESULTS: Regression analyses found moderation of group differences by RS for three outcomes: social participation, self-perceptions of social acceptance, and externalizing behavior problems. Conditional effects at varying levels of RS indicated that externalizing problems and social participation were significantly worse for children with STBI at high levels of RS, compared to children with OI. Social participation for the STBI group remained significantly lower than the OI group at mean levels of RS, but not at low levels of RS. At high levels of RS, self-perceptions of social acceptance were lower for children with moderate TBI compared to OI, but group differences were not significant at mean or low levels of RS. No evidence of moderation was found for global self-worth, self-perceptions of physical appearance or athletic ability, or internalizing problems. CONCLUSIONS: The findings highlight the salient nature of social outcomes in the context of varying levels of RS. These findings may have implications for the design of interventions to improve social outcomes following TBI. (JINS, 2017, 23, 451-459).

Profiles of Executive Function Across Children with Distinct Brain Disorders: Traumatic Brain Injury, Stroke, and Brain Tumor.

OBJECTIVES: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. METHODS: Participants were children with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke (N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch) subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. RESULTS: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. CONCLUSIONS: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).

Brain biomarkers and pre-injury cognition are associated with long-term cognitive outcome in children with traumatic brain injury.

BACKGROUND: Children with traumatic brain injury (TBI) are frequently at risk of long-term impairments of attention and executive functioning but these problems are difficult to predict. Although deficits have been reported to vary with injury severity, age at injury and sex, prognostication of outcome remains imperfect at a patient-specific level. The objective of this proof of principle study was to evaluate a variety of patient variables, along with six brain-specific and inflammatory serum protein biomarkers, as predictors of long-term cognitive outcome following paediatric TBI. METHOD: Outcome was assessed in 23 patients via parent-rated questionnaires related to attention deficit hyperactivity disorder (ADHD) and executive functioning, using the Conners 3rd Edition Rating Scales (Conners-3) and Behaviour Rating Inventory of Executive Function (BRIEF) at a mean time since injury of 3.1 years. Partial least squares (PLS) analyses were performed to identify factors measured at the time of injury that were most closely associated with outcome on (1) the Conners-3 and (2) the Behavioural Regulation Index (BRI) and (3) Metacognition Index (MI) of the BRIEF. RESULTS: Higher levels of neuron specific enolase (NSE) and lower levels of soluble neuron cell adhesion molecule (sNCAM) were associated with higher scores on the inattention, hyperactivity/impulsivity and executive functioning scales of the Conners-3, as well as working memory and initiate scales of the MI from the BRIEF. Higher levels of NSE only were associated with higher scores on the inhibit scale of the BRI. CONCLUSIONS: NSE and sNCAM show promise as reliable, early predictors of long-term attention-related and executive functioning problems following paediatric TBI.

Are Shunt Revisions Associated with IQ in Congenital Hydrocephalus? A Meta -Analysis.

Although it is generally acknowledged that shunt revisions are associated with reductions in cognitive functions in individuals with congenital hydrocephalus, the literature yields mixed results and is inconclusive. The current study used meta-analytic methods to empirically synthesize studies addressing the association of shunt revisions and IQ in individuals with congenital hydrocephalus. Six studies and three in-house datasets yielded 11 independent samples for meta-analysis. Groups representing lower and higher numbers of shunt revisions were coded to generate effect sizes for differences in IQ scores. Mean effect size across studies was statistically significant, but small (Hedges' g = 0.25, p < 0.001, 95 % CI [0.08, 0.43]) with more shunt revisions associated with lower IQ scores. Results show an association of lower IQ and more shunt revisions of about 3 IQ points, a small effect, but within the error of measurement associated with IQ tests. Although clinical significance of this effect is not clear, results suggest that repeated shunt revisions because of shunt failure is associated with a reduction in cognitive functions.

Investigating a Proposed Model of Social Competence in Children With Traumatic Brain Injuries.

OBJECTIVE: The goal of the current study was to test a proposed model of social competence for children who have suffered a traumatic brain injury (TBI). We hypothesized that both peer and teacher reports of social behavior would mediate the relation between intraindividual characteristics (e.g., executive function) and peer acceptance. METHODS: Participants were 52 children with TBI (M age = 10.29; M time after injury: 2.46 years). Severity of TBI ranged from complicated mild to severe. Classroom and laboratory measures were used to assess executive function, social behavior, and peer acceptance. RESULTS: Analyses revealed that peer reports of social behavior were a better mediator than teacher reports of the associations between executive function, social behaviors, and peer acceptance. DISCUSSION: The results underscore the importance of including peer reports of social behavior when developing interventions designed to improve the social, emotional, and behavioral outcomes of children with TBI.

Serum Biomarkers Help Predict Attention Problems in Critically Ill Children With Traumatic Brain Injury.

OBJECTIVE: To evaluate the association between acute serum biomarkers, and the changes in attention at 1 year following traumatic brain injury. DESIGN AND SETTING: A prospective observational and laboratory study conducted in PICUs at five Canadian children's hospitals. STUDY POPULATION AND MEASUREMENTS: Fifty-eight patients aged 5 to 17 years with traumatic brain injury were enrolled in the study. Nine brain-specific and inflammatory serum protein biomarkers were measured multiple times over the first week following injury. Attention was measured at "baseline" to represent pre-injury function and at 1 year following injury using the Conners Third Parent Rating Scale. RESULTS: Compared with baseline, there were significantly more clinical symptoms of inattention at 1 year post injury. The Glasgow Coma Scale score, age at injury, baseline levels of inattention, and highest levels of serum biomarkers were used to estimate the probability of developing inattention. These independent variables were first evaluated individually followed by combinations of the best predictors using area under the receiver operating characteristic curve analyses. A combination of high baseline levels of inattention and high serum levels of the biomarker neuron-specific enolase was the best predictor for inattention. Glasgow Coma Scale and age at injury were not associated with inattention at 1 year post injury. CONCLUSIONS: Combining baseline assessment of attention with measurement of serum biomarkers shows promise as reliable, early predictors of long-term attention after childhood traumatic brain injury.

Children with Traumatic Brain Injury: Associations Between Parenting and Social Adjustment.

Similarities and differences in parenting practices of children (Mage = 10; range 8-13 years) with traumatic brain injury (TBI) and socially-typical controls were examined. In addition, parenting practices were examined as moderators between injury group status (TBI or socially-typical) and social adjustment in the peer group. Mothers completed assessments of parenting practices; children's peers reported about children's social adjustment. The mothers of children with TBI reported significantly lower levels of nurturance and significantly higher levels of restrictiveness than mothers of socially-typical children. In addition, mothers' nurturance moderated the relation between injury group and peer rejection, such that children with TBI were more rejected by classmates compared to their socially-typical peers at low levels of maternal nurturance. The findings are interpreted as supporting the important role parents play in the development of children with a history of TBI, as well as the implications for family-level interventions.

Personality Change Due to Traumatic Brain Injury in Children and Adolescents: Neurocognitive Correlates.

Personality change due to traumatic brain injury (PC) in children is an important psychiatric complication of injury and is a form of severe affective dysregulation. This study aimed to examine neurocognitive correlates of PC. The sample included 177 children 5-14 years old with traumatic brain injury who were enrolled from consecutive admissions to five trauma centers. Patients were followed up prospectively at baseline and at 6 months, and they were assessed with semistructured psychiatric interviews. Injury severity, socioeconomic status, and neurocognitive function (measures of attention, processing speed, verbal memory, IQ, verbal working memory, executive function, naming/reading, expressive language, motor speed, and motor inhibition) were assessed with standardized instruments. Unremitted PC was present in 26 (18%) of 141 participants assessed at 6 months postinjury. Attention, processing speed, verbal memory, IQ, and executive function were significantly associated with PC even after socioeconomic status, injury severity, and preinjury attention deficit hyperactivity disorder were controlled. These findings are a first step in characterizing concomitant cognitive impairments associated with PC. The results have implications beyond brain injury to potentially elucidate the neurocognitive symptom complex associated with mood instability regardless of etiology.

Psychiatric disorders in children and adolescents 24 months after mild traumatic brain injury.

This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5-14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning.

Self-awareness of peer-rated social attributes in children with traumatic brain injury.

OBJECTIVE: This study investigated self-awareness of peer-rated social attributes and its relations to executive function (EF), theory of mind (TOM), and psychosocial adjustment in children with traumatic brain injury (TBI). METHODS: Self- and peer perceptions of classroom social behavior were assessed for 87 children 8-13 years of age: 15 with severe TBI, 40 with complicated mild/moderate TBI, and 32 with orthopedic injury. Participants completed measures of EF and TOM, and parents rated children's psychosocial adjustment. RESULTS: Self-ratings of classroom social behavior did not differ between injury groups. Self- and peer ratings generally agreed, although children with severe TBI rated themselves as less rejected/victimized than did their peers. Higher EF predicted better self- and peer ratings and smaller self-peer discrepancies, which in turn predicted better adjustment. CONCLUSIONS: Children with TBI show variable social self-awareness, which relates to EF and adjustment. Future studies should identify additional factors that contribute to limited insight.

Social problem-solving and social adjustment in paediatric traumatic brain injury.

OBJECTIVE: Little is known regarding the predictors of social deficits that occur following childhood traumatic brain injury (TBI). The current study sought to investigate social problem solving (SPS) and its relationship to social adjustment after TBI. METHODS: Participants included 8-13 year old children, 25 with severe TBI, 57 with complicated mild-to-moderate TBI and 61 with orthopaedic injuries (OI). Children responded to scenarios involving negative social situations by selecting from a fixed set of choices their causal attribution for the event, their emotional reaction to the event and how they would behave in response. Parent ratings of social behaviours and classmate friendship nominations and sociometric ratings were obtained for a sub-set of all participants. RESULTS: Children with severe TBI were less likely than children with OI to indicate they would attribute external blame or respond by avoiding the antagonist; they were more likely to indicate they would feel sad and request adult intervention. Although several SPS variables had indirect effects on the relationship between TBI and social adjustment, clinical significance was limited. CONCLUSIONS: The findings suggest that, while children with TBI display atypical SPS skills, SPS cannot be used in isolation to accurately predict social adjustment.

Day of injury CT and late MRI findings: Cognitive outcome in a paediatric sample with complicated mild traumatic brain injury.

OBJECTIVES: Complicated mild traumatic brain injury (mTBI) or cmTBI is based on the presence of visibly identifiable brain pathology on the day-of-injury computed tomography (CT) scan. In a paediatric sample the relation of DOI CT to late MRI findings and neuropsychological outcome was examined. METHODS: MRI (>12 months) was obtained in paediatric cmTBI patients and a sample of orthopaedically injured (OI) children. Those children with positive imaging findings (MRI+) were quantitatively compared to those without (MRI-) or with the OI sample. Groups were also compared in neurocognitive outcome from WASI sub-tests and the WISC-IV Processing Speed Index (PSI), along with the Test of Everyday Attention for Children (TEA-Ch) and a parent-rated behavioural functioning measure (ABAS-II). RESULTS: Despite the MRI+ group having significantly more DOI CT findings than the MRI- group, no quantitative differences were found. WASI Vocabulary and Matrix Reasoning scores were significantly lower, but not PSI, TEA-Ch or ABAS-II scores. MRI+ and MRI- groups did not differ on these measures. CONCLUSIONS: Heterogeneity in the occurrence of MRI-identified focal pathology was not associated with uniform changes in quantitative analyses of brain structure in cmTBI. Increased number of DOI CT abnormalities was associated with lowered neuropsychological performance.

Functional plasticity in childhood brain disorders: when, what, how, and whom to assess.

At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome.

Covert orienting in three etiologies of congenital hydrocephalus: the effect of midbrain and posterior fossa dysmorphology.

Covert orienting is related to the integrity of the midbrain, but the specificity of the relation is unclear. We compared covert orienting in three etiologies of congenital hydrocephalus (aqueductal stenosis [AS], Dandy-Walker malformation [DWM], and spina bifida myelomeningocele [SBM]--with and without tectal beaking) to explore the effects of midbrain and posterior fossa malformations. We hypothesized a stepwise order of group performance reflecting the degree of midbrain tectum dysmorphology. Performance on an exogenously cued covert orienting task was compared using repeated measures analysis of covariance, controlling for age. Individuals with SBM and tectal beaking demonstrated the greatest disengagement cost in the vertical plane, whereas individuals with AS performed as well as a typically developing (TD) group. Individuals with SBM but no tectal beaking and individuals with DWM showed greater disengagement costs in the vertical plane relative to the TD group, but better performance relative to the group with SBM and tectal beaking. Individuals with AS, DWM, and SBM and tectal beaking demonstrated poorer inhibition of return than TD individuals. Impairments in attentional disengagement in SBM are not attributable to the general effects of hydrocephalus, but are instead associated with specific midbrain anomalies that are part of the Chiari II malformation.

Friendship quality and psychosocial outcomes among children with traumatic brain injury.

This study examined differences in friendship quality between children with traumatic brain injury (TBI) and orthopedic injury (OI) and behavioral outcomes for children from both groups. Participants were 41 children with TBI and 43 children with OI (M age=10.4). Data were collected using peer- and teacher-reported measures of participants' social adjustment and parent-reported measures of children's post-injury behaviors. Participants and their mutually nominated best friends also completed a measure of the quality of their friendships. Children with TBI reported significantly more support and satisfaction in their friendships than children with OI. Children with TBI and their mutual best friend were more similar in their reports of friendship quality compared to children with OI and their mutual best friends. Additionally, for children with TBI who were rejected by peers, friendship support buffered against maladaptive psychosocial outcomes, and predicted skills related to social competence. Friendship satisfaction was related to higher teacher ratings of social skills for the TBI group only. Positive and supportive friendships play an important role for children with TBI, especially for those not accepted by peers. Such friendships may protect children with TBI who are rejected against maladaptive psychosocial outcomes, and promote skills related to social competence.

Neuropsychological performance of youth with secondary attention-deficit/hyperactivity disorder 6- and 12-months after traumatic brain injury.

The present study compared executive dysfunction among children with attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (S-ADHD), pre-injury ADHD and children with TBI only (i.e., no ADHD). Youth aged 6-16 years admitted for TBI to five trauma centers were enrolled (n=177) and evaluated with a semi-structured psychiatric interview scheduled on three occasions (within 2 weeks of TBI, i.e., baseline assessment for pre-injury status; 6-months and 12-months post-TBI). This permitted the determination of 6- and 12-month post-injury classifications of membership in three mutually exclusive groups (S-ADHD; pre-injury ADHD; TBI-only). Several executive control measures were administered. Unremitted S-ADHD was present in 17/141 (12%) children at the 6-month assessment, and in 14/125 (11%) children at 12-months post-injury. The study found that children with S-ADHD exhibited deficient working memory, attention, and psychomotor speed as compared to children with pre-injury ADHD. Furthermore, the children with S-ADHD and the children with TBI-only were impaired compared to the children with pre-injury ADHD with regard to planning. No group differences related to response inhibition emerged. Age, but not injury severity, gender, or adaptive functioning was related to executive function outcome. Neuropsychological sequelae distinguish among children who develop S-ADHD following TBI and those with TBI only. Moreover, there appears to be a different pattern of executive control performance in those who develop S-ADHD than in children with pre-injury ADHD suggesting that differences exist in the underlying neural mechanisms that define each disorder, underscoring the need to identify targeted treatment interventions.

Functional significance of atypical cortical organization in spina bifida myelomeningocele: relations of cortical thickness and gyrification with IQ and fine motor dexterity.

The cortex in spina bifida myelomeningocele (SBM) is atypically organized, but it is not known how specific features of atypical cortical organization promote or disrupt cognitive and motor function. Relations of deviant cortical thickness and gyrification with IQ and fine motor dexterity were investigated in 64 individuals with SBM and 26 typically developing (TD) individuals, aged 8-28 years. Cortical thickness and 3D local gyrification index (LGI) were quantified from 33 cortical regions per hemisphere using FreeSurfer. Results replicated previous findings, showing regions of higher and lower cortical thickness and LGI in SBM relative to the TD comparison individuals. Cortical thickness and LGI were negatively associated in most cortical regions, though less consistently in the TD group. Whereas cortical thickness and LGI tended to be negatively associated with IQ and fine motor outcomes in regions that were thicker or more gyrified in SBM, associations tended to be positive in regions that were thinner or less gyrified in SBM. The more deviant the levels of cortical thickness and LGI-whether higher or lower relative to the TD group-the more impaired the IQ and fine motor outcomes, suggesting that these cortical atypicalities in SBM are functionally maladaptive, rather than adaptive.

Neuropsychological profiles of children with aqueductal stenosis and Spina Bifida myelomeningocele.

We compared neuropsychological profiles in children with shunted hydrocephalus secondary to aqueductal stenosis (AS), a rare form of congenital hydrocephalus, and spina bifida myelomeningocele (SBM), a common form of congenital hydrocephalus. Participants were 180 children with shunted hydrocephalus grouped according to etiology: SBM (n = 151), AS (n = 29), and typically developing (TD; n = 60) individuals. The group with AS performed below the TD group on all tasks except for reading, and their overall performance was higher than the group with SBM, who had the lowest performance in the sample. Both clinical groups significantly differed from the TD group on tasks of spatial function, concept formation, motor function, and memory. Performance of the subgroup of AS children with normal cerebellum status approximated that of the TD group, while those with cerebellar anomalies performed lower than others with AS. Cerebellar abnormalities (present in the whole SBM group and in a subset of the AD group) are associated with more compromise of cognitive as well as motor function.