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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.

Traumatic brain injury (TBI) is known to contribute to deficits in executive functioning (EF). Executive functioning abilities are disrupted in adolescents with either conduct disorder or o...

BACKGROUND: Traumatic brain injury (TBI) is associated with considerable mortality and morbidity in adolescents, but positive outcomes are possible. Resilience is the concept that some individuals flourish despite significant adversity. OBJECTIVE: To determine if there is a relationship between resilience-promoting factors that are known to promote resilience and white matter microstructure 1 year after complicated mild TBI or moderate or severe TBI that is sustained by adolescents. METHOD: We examined the relationship between performance on a self-report measure of resilience-promoting factors and white matter integrity assessed by diffusion tensor imaging (DTI) in a group of adolescents who had sustained either a TBI (n = 38) or an orthopedic injury (OI) (n = 23). RESULTS: Immediately following injury, the individuals with TBI and the OI controls had comparable levels of resilience-promoting factors; however, at 1 year post injury, the TBI group endorsed fewer resilience-promoting factors and exhibited white matter disruption compared with the OI controls. The individuals with TBI who had more resilience-promoting factors at 1 year post injury exhibited increased white matter integrity, but the OI controls did not. Findings were particularly strong for the following structures: anterior corona radiata, anterior limb of the internal capsule, and genu of the corpus callosum—structures that are implicated in social cognition and are frequently disrupted after TBI. Relationships were notable for caregiver and community-level resilience-promoting factors. CONCLUSION: The current findings are some of the first to indicate neurobiological evidence of previously noted buffering effects of resilience-promoting factors in individuals with TBI.

The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity.Between a paediatric group with TBI and a group of typically-developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity.Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to-severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests.The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching).TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits.

Microstructural neuropathology occurs in the corpus callosum (CC) after repetitive sports concussion in boxers and can be dose-dependent. However, the specificity and relation of CC changes to boxing exposure extent and post-career psychiatric and neuropsychological outcomes are largely unknown. Using deterministic diffusion tensor imaging (DTI) techniques, boxers and demographically-matched, noncontact sport athletes were compared to address literature gaps. Ten boxers and 9 comparison athletes between 26 and 59 years old (M = 44.63, SD = 9.24) completed neuropsychological testing and MRI. Quantitative DTI metrics were estimated for CC subregions. Group×Region interaction effects were observed on fractional anisotropy (FA; η2p ≥ .21). Follow-up indicated large effects of group (η2p ≥ .26) on splenium FA (boxers comparisons), but not radial diffusivity (RD). The group of boxers had moderately elevated number of psychiatric symptoms and reduced neuropsychological scores relative to the comparison group. In boxers, years sparring, professional bouts, and knockout history correlated strongly (r > |.40|) with DTI metrics and fine motor dexterity. In the comparison group, splenium FA correlated positively with psychiatric symptoms. In the boxer group, neuropsychological scores correlated with DTI metrics in all CC subregions. Results suggested relative vulnerability of the splenium and, to a lesser extent, the genu to chronic, repetitive head injury from boxing. Dose-dependent associations of professional boxing history extent with DTI white matter structure indices as well as fine motor dexterity were supported. Results indicated that symptoms of depression and executive dysfunction may provide the strongest indicators of global CC disruption from boxing.

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.

Although most patients with mild traumatic brain injury (mTBI) recover within 3 months, a subgroup of patients experience persistent symptoms. Yet, the prevalence and predictors of persistent dysfunction in patients with mTBI remain poorly understood. In a longitudinal study, we evaluated predictors of symptomatic and cognitive dysfunction in adolescents and young adults with mTBI, compared with two control groups-patients with orthopedic injuries and healthy uninjured individuals. Outcomes were assessed at 3 months post-injury. Poor symptomatic outcome was defined as exhibiting a symptom score higher than 90% of the orthopedic control (OC) group, and poor cognitive outcome was defined as exhibiting cognitive performance poorer than 90% of the OC group. At 3 months post-injury, more than half of the patients with mTBI (52%) exhibited persistently elevated symptoms, and more than a third (36.4%) exhibited poor cognitive outcome. The rate of high symptom report in mTBI was markedly greater than that of typically developing (13%) and OC (17%) groups; the proportion of those with poor cognitive performance in the mTBI group exceeded that of typically developing controls (15.8%), but was similar to that of the OC group (34.9%). Older age at injury, female sex, and acute symptom report were predictors of poor symptomatic outcome at 3 months. Socioeconomic status was the only significant predictor of poor cognitive outcome at 3 months.

OBJECTIVE AND BACKGROUND: We examined sleep-related problems in adolescents and young adults after a mild traumatic brain injury (MTBI) or orthopedic injury. We extended the analysis of data from a study of early emotional and neuropsychological sequelae in these populations (McCauley et al. 2014. J Neurotrauma. 31:914). METHODS: We gave the Pittsburgh Sleep Quality Index to 77 participants with MTBI, 71 with orthopedic injury, and 43 non-injured controls. The age range was 12 to 30 years. We tested sleep quality within 96 hours of injury and at 1- and 3-month follow-up. Participants also completed measures of pain and fatigue, drug and alcohol use, and post-traumatic stress symptoms. RESULTS: Older participants (mean age=25 years) in the MTBI group exhibited a sharp increase in sleep-related symptoms between the baseline assessment and 1 month, and still had difficulties at 3 months. Younger participants with MTBI (mean age=15 years) and older participants with an orthopedic injury had modest increases in sleep difficulties between baseline and 1 month. The participants with MTBI also had more clinically significant sleep difficulties at all 3 assessments. At 3 months, Pittsburgh Sleep Quality Index scores in younger participants with MTBI and all participants with orthopedic injury did not differ significantly from the non-injured controls'. The controls had no significant change in their sleep symptoms during the 3 months. CONCLUSIONS: Sleep difficulties in young adults may persist for ≤3 months after MTBI and exceed those after orthopedic injury. Clinicians should seek and treat sleep-related problems after MTBI. Language: en

Although mild traumatic brain injury (mTBI) is now recognized as a major health issue, there have been relatively few studies of its acute effects. Previous studies of mTBI assessed at 1 week or less post-injury have produced inconsistent results, spanning reports of no ill effects to findings of robust dysfunction. These gross disparities reflect study differences such as the criteria for mTBI diagnosis and selection of comparison groups. In consideration of these issues, this study investigated outcome in the first 96 hours after injury in adolescents and adults ages 12-30 years with mTBI (n=73) compared with orthopedically injured (OI, n=65) and typically developing controls (TDC, n=40). The mTBI group reported significantly greater general psychological distress, post-concussion symptom severity, and post-traumatic stress severity than OI (all p

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition.

Purpose – The study is a preliminary attempt to identify cognitive factors (e.g., executive functions and intelligence) promoting resilience in youth in an underprivileged population. Sample consisted of 26 adolescents (seven female, 19 male) between the ages of 13 and 19 years (M=16.62, SD=1.53) from an underserved population who live in circumstances of poverty and family dysfunction and who had experienced multiple traumas. Design/methodology/approach – Resilience was measured with the Child and Youth Resilience Measure (CYRM)-28. Intelligence, working memory, and information processing speed were the cognitive factors of interest. Socioeconomic status was the environmental factor in interest. Findings – The protective factors (i.e. individual skills, relationship with caregivers and contextual factors) promoting resilience were correlated with cognitive factors. Further analyses yielded gender differences in these relations. Originality/value – Long-held beliefs that intelligence is positively associated with resilience are brought into question by these findings. The relationship between these concepts seems to differ in accordance with socioeconomic status.

Low birth weight (LBW; below 2500 grams) is a general risk factor for a variety of neurodevelopmental difficulties. However, these children may remain more vulnerable to neurologic and environmental insults occurring years later. This prospective case series reports on children who sustained a mild, moderate, or severe traumatic brain injury (TBI) in middle childhood but who had also been born with birth weights below 2500 grams.PARTICIPANTS were 14 children with mild, moderate, or severe traumatic brain injury (TBI), 5 of whom had birth weights under 2500 grams (LBW) and 9 children with normal birth weight (NBW). All participants were drawn from a larger study on the long-term cognitive and behavioral impact of pediatric TBI and were matched on age, estimated socioeconomic status (SES), and severity of TBI (with NBW children actually having a slightly worse overall injury severity).At baseline, both groups exhibited similar scores on WJ-R Letter Word Identification and Calculations, Tower of London number solved, and CVLT-C total correct. Baseline group differences were observed on the CELF-III Formulated Sentences (NBWLBW) and on the VABS Adaptive Behavior Composite and Socialization subdomain (LBWNBW). Over 2 years, relative to the NBW group, the LBW group evidenced declines on both WJ-R subtests, CVLT-C total correct, CELF-III Formulated Sentences, and VABS Adaptive Behavior Composite and Socialization.Although preliminary in nature due to small sample size, findings suggest a history of LBW influences the recovery trajectory following childhood TBI. Academic and adaptive functioning and verbal memory appeared particularly affected.

The objective was to assess the nature, rate, predictive factors, and neurocognitive correlates of novel psychiatric disorders (NPD) after mild traumatic brain injury (MTBI). Children age 5-14 years with MTBI (N=87) from consecutive admissions to five trauma centers were enrolled and studied with semistructured psychiatric interviews soon after injury (baseline), and 70 of these children were assessed again 6 months post-injury. Injury severity; lesion characteristics; pre-injury variables, including psychiatric disorder, family psychiatric history, family functioning, socioeconomic status, psychosocial adversity, and adaptive functioning; and post-injury neurocognitive and adaptive functioning measures were assessed with standardized instruments. NPD occurred in 25 of 70 participants (36%) in the first 6 months after injury. NPD at 6 months was predicted by the presence of frontal white-matter lesions on MRI at 3 months post-injury, and was associated with concurrent decrements on neurocognitive indices of processing speed, expressive language, and intellectual functioning. NPD was not predicted by other indices of severity, pre-injury psychosocial variables, estimated pre-injury academic functioning, or adaptive and executive function decrements 6 months post-injury. These findings suggest that short-term psychiatric morbidity associated with MTBI in children and adolescents may be more common than previously thought and may have readily identifiable neuroimaging and neurocognitive correlates.

Few studies have examined the trajectory of recovery of executive function (EF) after mild TBI (mTBI). Therefore, consensus has not been reached on the incidence and extent of EF impairment after mTBI. The present study investigated trajectory of change in executive memory over 3 months after mTBI on 59 right-handed participants with mTBI, as defined by Centers for Disease Control criteria, ages 14–30 years, recruited within 96 hours post-injury and tested

For this pilot study, we compared performance of 15 adolescents with moderate–severe traumatic brain injury (TBI) to that of 13 typically developing (TD) adolescents in predicting social actions and consequences for avatars in a virtual microworld environment faced with dilemmas involving legal or moral infractions. Performance was analyzed in relation to cortical thickness in brain regions implicated in social cognition. Groups did not differ in number of actions predicted nor in reasons cited for predictions when presented only the conflict situation. After viewing the entire scenario, including the choice made by the avatar, TD and TBI adolescents provided similar numbers of short-term consequences. However, TD adolescents provided significantly more long-term consequences (p = .010). Additionally, for the Overall qualitative score, TD adolescents’ responses were more likely to reflect the long-term impact of the decision made (p = .053). Groups differed in relation of the Overall measure to thickness of right medial prefrontal cortex/frontal pole and precuneus, with stronger relations for the TD group (p < .01). For long-term consequences, the relations to the posterior cingulate, superior medial frontal, and precentral regions, and to a lesser extent, the middle temporal region, were stronger for the TBI group (p < .01). (JINS, 2013, 19, 1–10.)

The purpose of this study was to assess patterns of cortical development over time in children who had sustained traumatic brain injury (TBI) as compared to children with orthopedic injury (OI), and to examine how these patterns related to emotional control and behavioral dysregulation, two common post-TBI symptoms. Cortical thickness was measured at approximately 3 and 18 months post-injury in 20 children aged 8.2-17.5 years who had sustained moderate-to-severe closed head injury and 21 children aged 7.4-16.7 years who had sustained OI. At approximately 3 months post-injury, the TBI group evidenced decreased cortical thickness bilaterally in aspects of the superior frontal, dorsolateral frontal, orbital frontal, and anterior cingulate regions compared to the control cohort, areas of anticipated vulnerability to TBI-induced change. At 18 months post-injury, some of the regions previously evident at 3 months post-injury remained significantly decreased in the TBI group, including bilateral frontal, fusiform, and lingual regions. Additional regions of significant cortical thinning emerged at this time interval (bilateral frontal regions and fusiform gyrus and left parietal regions). However, differences in other regions appeared attenuated (no longer areas of significant cortical thinning) by 18 months post-injury including large bilateral regions of the medial aspects of the frontal lobes and anterior cingulate. Cortical thinning within the OI group was evident over time in dorsolateral frontal and temporal regions bilaterally and aspects of the left medial frontal and precuneus, and right inferior parietal regions. Longitudinal analyses within the TBI group revealed decreases in cortical thickness over time in numerous aspects throughout the right and left cortical surface, but with notable "sparing" of the right and left frontal and temporal poles, the medial aspects of both the frontal lobes, the left fusiform gyrus, and the cingulate bilaterally. An analysis of longitudinal changes in cortical thickness over time (18 months-3 months) in the TBI versus OI group demonstrated regions of relative cortical thinning in the TBI group in bilateral superior parietal and right paracentral regions, but relative cortical thickness increases in aspects of the medial orbital frontal lobes and bilateral cingulate and in the right lateral orbital frontal lobe. Finally, findings from analyses correlating the longitudinal cortical thickness changes in TBI with symptom report on the Emotional Control subscale of the Behavior Rating Inventory of Executive Function (BRIEF) demonstrated a region of significant correlation in the right medial frontal and right anterior cingulate gyrus. A region of significant correlation between the longitudinal cortical thickness changes in the TBI group and symptom report on the Behavioral Regulation Index was also seen in the medial aspect of the left frontal lobe. Longitudinal analyses of cortical thickness highlight an important deviation from the expected pattern of developmental change in children and adolescents with TBI, particularly in the medial frontal lobes, where typical patterns of thinning fail to occur over time. Regions which fail to undergo expected cortical thinning in the medial aspects of the frontal lobes correlate with difficulties in emotional control and behavioral regulation, common problems for youth with TBI. Examination of post-TBI brain development in children may be critical to identification of children that may be at risk for persistent problems with executive functioning deficits and the development of interventions to address these issues.

The aim of the study was to examine longitudinal patterns of decision making based on risk and reward using a modified version of the Iowa Gambling Task (IGT) in children who had sustained traumatic brain injury (TBI) and children with orthopedic injury (OI). Participants were 135 children and adolescents with TBI (n=71) or OI (n=64) who were 7-17 years at the time of injury were enrolled and assessed prospectively at baseline and at follow-up intervals of 3, 12, 18, and 24 months after injury. Groups were similar in age, socioeconomic status, and gender. Participants chose from four decks of cards with the aim of maximizing earnings across 100 trials. Two of the decks offered relatively small rewards and relatively small losses, but were advantageous over the course of the experiment. The other two decks offered large rewards, but also introduced occasional large losses, and were considered disadvantageous over the course of the experiment. The variable of interest was the proportion of advantageous decks chosen across trials. Longitudinal analysis of the pattern of change across 2 years revealed a three-way interaction among injury group, age, and the quadratic term of interval-since-injury. In this interaction, the effect of age weakened in the TBI group across time, as compared to the OI group, which showed stronger quadratic patterns across the recovery intervals that differed by age. The OI group generally outperformed the TBI group. In addition, analyses revealed a three-way interaction among group, gender and the cubic term of post-injury interval, such that overall, males improved a great deal with time, but females showed small gains, regardless of injury group.

Neural correlates of working memory (WM) based on the Sternberg Item Recognition Task (SIRT) were assessed in 40 children with moderate-to-severe traumatic brain injury (TBI) compared to 41 demographically-comparable children with orthopedic injury (OI). Multiple magnetic resonance imaging (MRI) methods assessed structural and functional brain correlates of WM, including volumetric and cortical thickness measures on all children; functional MRI (fMRI) and diffusion tensor imaging (DTI) were performed on a subset of children. Confirming previous findings, children with TBI had decreased cortical thickness and volume as compared to the OI group. Although the findings did not confirm the predicted relation of decreased frontal lobe cortical thickness and volume to SIRT performance, left parietal volume was negatively related to reaction time (RT). In contrast, cortical thickness was positively related to SIRT accuracy and RT in the OI group, particularly in aspects of the frontal and parietal lobes, but these relationships were less robust in the TBI group. We attribute these findings to disrupted fronto-parietal functioning in attention and WM. fMRI results from a subsample demonstrated fronto-temporal activation in the OI group, and parietal activation in the TBI group, and DTI findings reflected multiple differences in white matter tracts that engage fronto-parietal networks. Diminished white matter integrity of the frontal lobes and cingulum bundle as measured by DTI was associated with longer RT on the SIRT. Across modalities, the cingulate emerged as a common structure related to performance after TBI. These results are discussed in terms of how different imaging modalities tap different types of pathologic correlates of brain injury and their relationship with WM.

The integrity of the fornix using diffusion tensor imaging (DTI) in adolescent participants with acute mild traumatic brain injury (mTBI) compared to a demographically matched control group was examined. Fractional anisotropy (FA) in the fornix was elevated in the mild traumatic brain injured group. Performance on the Automated Neuropsychological Assessment Metrics (ANAM) was lower in the group with mTBI. A relation was found between lower performance on cognitive tasks and higher FA. The potential role of fornix injury as a basis of memory and processing speed deficits in mTBI is discussed.

Children with closed head injuries often experience significant and persistent disruptions in their social and behavioral functioning. Studies with adults sustaining a traumatic brain injury (TBI) indicate deficits in emotion recognition and suggest that these difficulties may underlie some of the social deficits. The goal of the current study was to examine if children sustaining a TBI exhibit difficulties with emotion recognition in terms of emotional prosody and face emotion recognition and to determine (1) how these abilities change over time and (2) what, if any, additional factors such as sex, age, and socioeconomic status (SES) affected the findings. Results provide general support for the idea that children sustaining a TBI exhibit deficits in emotional prosody and face emotion recognition performance. Further, although some gains were noted in the TBI group over the two-years following injury, factors such as SES and age at injury influenced the trajectory of recovery. The current findings indicate the relationship between TBI and emotion recognition is complex and may be influenced by a number of developmental and environmental factors. Results are discussed in terms of their similarity to previous investigations demonstrating the influence of environmental factors on behavioral recovery following pediatric TBI, and with regard to future investigations that can further explore the link between emotion recognition deficits and long-term behavioral and psychosocial recovery.

Compromised memory functioning is one of the commonly reported cognitive sequelae seen following mild traumatic brain injury (mTBI). Diffusion tensor imaging (DTI) has been shown to be sufficiently sensitive at detecting early microstructural pathological alterations after mTBI. Given its location and shape, the cingulate, which is comprised of the cingulate gyrus (gray matter) and cingulum bundles (white matter), is selectively vulnerable to mTBI. In this study we examined the integrity of cingulum bundles using DTI, and the relationship between cingulum bundles and memory functioning. Twelve adolescents with mTBI and 11 demographically-matched healthy controls were studied. All participants with mTBI had a Glasgow Coma Scale score of 15, and were without intracranial findings on CT scan. Brain scans were performed on average 2.92 days post-injury, and all participants were administered the Verbal Selective Reminding Test (VSRT), an episodic verbal learning and memory task. Participants with mTBI had a significantly lower apparent diffusion coefficient (ADC) bilaterally than controls (p

Oral reading and expressive language skills were examined in 2 cohorts of children aged 5–15 years, who had mild, moderate, or severe traumatic brain injury. Children recruited prospectively from time of injury were assessed on 5 occasions over 2 years in a longitudinal study of change in reading skills, using the Gray Oral Reading Test-3rd Edition, and in expressive language, using the Formulated Sentences subtest of the Clinical Evaluation of Language Fundamentals-3rd Edition. Contributions of related cognitive-linguistic skills were also examined. Children recruited retrospectively were studied on a single occasion in a cross-sectional design investigating the contribution of age-related variables to the reading and sentence formulation scores. Similar to previous studies of childhood traumatic brain injury, children injured when younger initially showed a more rapid rate of recovery but poorer overall performance on outcome measures than did children injured when older. Socioeconomic status strongly predicted outcome for both reading and expressive language.

Object The aim of this study was to determine whether the presence of intracranial pathophysiology on computed tomography (CT) scans obtained within 24 hours of mild traumatic brain injury (MTBI) in children adversely affects neuropsychological outcome during the 1st year postinjury. Methods A prospective longitudinal design was used to examine the neuropsychological outcomes in children (ages 5–15 years) who had been treated for MTBI, which was defined as a loss of consciousness for up to 30 minutes and a lowest Glasgow Coma Scale (GCS) score of 13–15. Exclusion criteria included any preinjury neurological disorder. Outcome assessments were performed within 2 weeks and at 3, 6, and 12 months postinjury. Outcomes were compared between patients with MTBI whose postinjury CT scans revealed complications of brain pathophysiology (32 patients, CMTBI group) and those with MTBI but without complications (48 patients, MTBI group). Results Significant interactions confirmed that the pattern of recovery over 12 months after injury differed depending on the intracranial pathology, presence and severity of injuries to body regions other than the head, preinjury attention-deficit hyperactivity disorder (ADHD), and socioeconomic status. Children in the CMTBI group had significantly poorer episodic memory, slower cognitive processing, diminished recovery in managing cognitive interference, and poorer performance in calculating and reading than patients in the MTBI group. Among the patients with mild or no extracranial injury, visuomotor speed was slower in those in the CMTBI group; and among patients without preinjury ADHD, working memory was worse in those in the CMTBI group. Conclusions Neuropsychological recovery during the 1st year following MTBI is related to the presence of radiographically detectable intracranial pathology. Children with intracranial pathology on acute CT performed more poorly in several cognitive domains when compared with patients whose CT findings were normal or limited to a linear skull fracture. Depending on the presence of preinjury ADHD and concomitant extracranial injury, working memory and visuomotor speed were also diminished in patients whose CT findings revealed complications following MTBI. Computed tomography within 24 hours postinjury appears to be useful for identifying children with an elevated risk for residual neuropsychological changes.

Eight adolescents (ages 13-18 years) who sustained traumatic brain injury (TBI) and eight gender- and age-matched typically developing (TD) adolescents underwent event-related functional MRI (fMRI) while performing a Sternberg letter recognition task. Encoding, maintenance, and retrieval were examined with memory loads of one or four items during imaging. Both groups performed above a 70% accuracy criterion and did not differ in performance. TD adolescents showed greater increase in frontal and parietal activation during high-load relative to low-load maintenance than the TBI group. The TBI patients showed greater increase in activation during high-load relative to low-load encoding and retrieval than the TD group. Results from this preliminary study suggest that the capability to differentially allocate neural resources according to memory load is disrupted by TBI for the maintenance subcomponent of working memory. The overrecruitment of frontal and extrafrontal regions during encoding and retrieval following TBI may represent a compensatory process.

Effects of pediatric traumatic brain injury (TBI) on social problem-solving were examined in a longitudinal study of 103 children with moderate-to-severe TBI (n = 52) or orthopedic injury (OI; n = 51) using the Interpersonal Negotiation Strategies task (INS). Children solved age-appropriate hypothetical social conflicts, with responses for four problem-solving steps scored by developmental level. The OI group performed better than the TBI group, but rate of change in performance over time did not differ between groups, suggesting improvement in children with TBI was not due to recovery from injury. Strong relations between INS performance and memory and language skills emerged, but emotional processing was only weakly related to INS performance. Frontal focal lesions influenced INS performance in younger (but not older) children with TBI. Diffusion tensor imaging (DTI), revealed strong relationships between the INS and increased apparent diffusion coefficient (ADC) measures indexing connectivity in the dorsolateral and cingulate regions in both TBI and OI groups, and in the temporal and parietal regions in the TBI group. These findings inform studies of social problem-solving skills during the first year post TBI. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

We investigated changes in inattentive and hyperactive symptoms over 2 years following traumatic brain injury (TBI) in relation to preinjury attention-deficit/hyperactivity disorder (ADHD), injury, and socioeconomic status (SES) variables. Postinjury stimulant medication treatment was also documented. Of 175 consecutive patients of ages 5 to 15 years with acute TBI, 148 consented, including 114 without preinjury ADHD (mean age, 10.0 years, SD = 2.76) and 34 with preinjury ADHD (mean age 10.36 years, SD = 2.75). The Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version, was administered at baseline and at 6, 12, and 24 months post-injury to assess the presence of nine core inattentive and nine hyperactive symptoms and associated impairment. The baseline assessment was performed within 1 month post-injury to establish preinjury diagnosis.Nonlinear change in inattentive symptoms in patients without preinjury ADHD contrasted with higher and more stable symptom levels in children with preinjury diagnosis, including the cubic trend (chi2(1) = 6.23, p = .0126). There was also a significant interaction of group x gender effect (chi2(1) = 4.08, p = .0435) as males had higher numbers of inattentive symptoms than females in the preinjury ADHD group. Change in hyperactive symptoms over time also differed by group, including both linear (chi2(1) = 5.42, p = .0199) and cubic trends (chi2(1) = 8.91, p = .0029), reflecting greater and more frequent fluctuations in children without preinjury ADHD. Socioeconomic level also contributed to change in hyperactive symptoms as reflected by the interaction of SES and linear time (chi2(1) = 6.91, p = .009), as well as quadratic time (chi2(1) = 4.90, p = .027). Occurrence of ADHD diagnosed post-injury ranged from 14.5% (12 months) to 18.3% (24 months) in the group without preinjury ADHD compared with a range from 86.4% (12 months) to 96.2% (6 months) in children with preinjury ADHD. In children without preinjury ADHD, SES was the only patient variable that predicted onset of ADHD, t(110) = -2.85, p = .0052. Treatment with stimulant medication post-injury was more frequently associated with preinjury ADHD (39% vs 7% of children without preinjury ADHD), p.0001 (Fisher exact test). Children with preinjury ADHD who were treated pre-injury with stimulant medication had fewer total symptoms at 24 months post-injury relative to untreated patients with preinjury ADHD (F[1,14] = 3.93, p = 0.069, Cohen's d = 1.28).Change in ADHD symptoms after TBI varies with preinjury diagnosis, reflects injury severity in children without preinjury ADHD, and is treated with stimulant medication mainly in those patients with preinjury ADHD.

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.

Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the microstructure of the cerebral white matter (WM) based on anisotropic diffusion (i.e., water molecules move faster in parallel to nerve fibers than perpendicular to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in adults with traumatic brain injury (TBI). However, previous DTI studies of pediatric TBI were case reports without detailed outcome measures. Using mean FA derived from DTI fiber tractography, we compared DTI findings of the corpus callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe TBI and individually matched, uninjured children. Interexaminer and intraexaminer reliability in measuring FA was satisfactory. FA was significantly lower in the patients for the genu, body, and splenium of the corpus callosum. Higher FA was related to increased cognitive processing speed and faster interference resolution on an inhibition task. In the TBI patients, higher FA was related to better functional outcome as measured by the dichotomized Glasgow Outcome Scale (GOS). FA also increased as a function of the area of specific regions of the corpus callosum such as the genu and splenium, and FA in the splenium was reduced with greater volume of lesions in this region. DTI may be useful in identifying biomarkers related to DAI and outcome of TBI in children.

To compare errorless learning with trial-and-error (TE) learning of declarative facts in children with memory disorders secondary to traumatic brain injury (TBI).Retrospective within-subjects concurrent treatment design.Participants' school or home.Thirty-four children, ages 6 to 18 years, with mild, moderate, or severe postacute TBI who met criteria for memory impairment.Conditions consisted of an errorless learning method and a TE method. Within a session, half the items were taught with the errorless learning method and half with the TE method. Each child received two 1-hour sessions a week for 7 weeks.Relative effectiveness of errorless learning and TE methods for (1) initial learning and (2) retention over time for learned items.There was an advantage for TE on initial learning. In children with mild, but not moderate or severe TBI, 2-day retention was better with the errorless learning technique; 7-day retention was better with errorless learning in young children with mild TBI. Seventy-seven-day retention revealed an advantage for errorless learning in younger children with severe TBI.Findings did not support errorless learning as a generalized intervention for learning difficulties after TBI or identify specific age- or injury-severity groups that benefited from this technique.

Emerging evidence suggests that a traumatic brain injury (TBI) in childhood may disrupt the ability to abstract the central meaning or gist-based memory from connected language (discourse). The current study adopts a novel approach to elucidate the role of immediate and working memory processes in producing a cohesive and coherent gist-based text in the form of a summary in children with mild and severe TBI as compared to typically developing children, ages 8-14 years at test. Both TBI groups showed decreased performance on a summary production task as well as retrieval of specific content from a long narrative. Working memory on n-back tasks was also impaired in children with severe TBI, whereas immediate memory performance for recall of a simple word list in both TBI groups was comparable to controls. Interestingly, working memory, but not simple immediate memory for a word list, was significantly correlated with summarization ability and ability to recall discourse content.

Inhibition was studied in 12 children who had had sustained as severe traumatic brain injury (TBI) at least 1 year earlier and in 15 control children. On the flanker task, which involved pressing a button corresponding to the direction of an arrow, the TBI group performed less accurately than controls under interference (flankers were incongruent with arrow) and go-no-go (adjacent stimulus signaled child to withhold response) conditions, but not neutral or facilitation (flankers were congruent) conditions. Response latency was related to age and task condition, but not group. Severe TBI in children may disrupt development of distributed networks mediating inhibition.

The impact of traumatic brain injury (TBI) on working memory (WM) was studied in 144 children (79 with mild, 23 with moderate, and 42 with severe injuries) who underwent magnetic resonance imaging (MRI) at 3 months and were tested at baseline and at 3, 6, 12, and 24 months postinjury. An n-back WM task for letter identity was administered with memory load ranging from 1- to 3-back and a 0-back condition. A TBI Severity x Quadratic Tune interaction showed that net percentage correct (correct detections of targets minus false alarms) was significantly lower in severe than in mild TBI groups. The Left Frontal Lesions x Age interaction approached significance. Mechanisms mediating late decline in WM and the effects of left frontal lesions are discussed.

Traumatic brain injury (TBI) in children has received increasing attention in recent years among parents, educators, clinicians and service providers, researchers and policymakers owing to the incidence and financial burden associated with injury during infancy, childhood or adolescence. Understanding the ways in which the immature brain may exhibit specific vulnerabilities to injury, how injury at a young age may interact with subsequent development, and anticipating the likely cognitive and functional consequences of child TBI is critical in detection of injury, monitoring recovery, and designing and evaluating rehabilitation strategies that may enhance recovery.

Selective learning (SL) is the ability to select items to learn from among other items. It requires the use of the executive processes of metacognitive control and working memory, which are considered to be mediated by the frontal cortex and its circuitry. We studied the efficiency with which verbal items of greater value are selectively learned from among items varying in value in 14 children ages 8-15 years who had sustained severe traumatic brain injury (TBI) and in 39 typically developing age-matched children. We hypothesized that children with TBI would be disproportionately compromised in selective learning efficiency in contrast to memory span when compared to normally developing children. The results supported our hypothesis, as children with TBI performed significantly worse than controls on a measure of selective learning efficiency, but the two groups performed similarly on a measure of word recall within the same task. Furthermore, the effect of TBI on performance was demonstrated to take place at the time of encoding, rather than at retrieval.

We examined relations of posttraumatic stress disorder (PTSD) symptoms with dimensions of trauma, including environment (Domestic vs. Community) and proximity (Indirect vs. Direct trauma) among inner-city youth. Participants (n = 65) reported traumatic events they had experienced on a version of the UCLA PTSD Reaction Index Trauma Exposure Screen, and reported PTSD symptoms with the PTSD Checklist—Civilian version (PCL-C). High rates of trauma and PTSD were found, consistent with other reports of inner-city youth. The 49% of youth surveyed met criteria for PTSD on the PCL-C symptom scale with a score cutoff of 35. Females reported elevated PTSD symptom scores and a higher incidence of Domestic trauma than did males but similar incidence of other trauma types. When males and females were combined, Domestic trauma significantly correlated with each of the PTSD symptom clusters of intrusions, numbing/avoidance, and hyperarousal. When participants with Community trauma were excluded from analyses to reduce confounding environmental influence, Domestic trauma marginally correlated with numbing/avoidance symptoms. Our findings suggest that Domestic trauma may result in more emotional numbing/avoidance symptoms than other types of trauma. Further analyses suggested that Community trauma may result in more intrusions and hyperarousal symptoms rather than emotional numbing. Environmental aspects of trauma, rather than the proximity of trauma, may have greater impact on presentation of PTSD. Future studies with larger samples are needed to confirm these findings.

A developmental case of phonological short-term memory deficit was studied in a highly educated subject. The subject, BS, who had obtained a Ph.D. in molecular biology, demonstrated striking deficits on some short-term memory tasks, particularly for auditorily presented nonword lists. With visual presentation and with meaningful words, he often scored at a normal level. The results indicate a deficit in retaining phonological information but an ability to use visual, lexical, and semantic information to boost recall. Despite this phonological short-term memory deficit, BS scored at a normal level on a syntactic comprehension test and on reading of nonwords. He was impaired, however, on repeated list learning, learning of foreign vocabulary, and transcribing dictated materials. The implications of these results for models of short-term memory and the uses of phonological retention in cognitive processing are discussed.

This paper reports the short-term memory and sentence processing performance of two head-injured children who were approximately 10 years of age at the time of test. The two children were found to have similarly reduced memory span on a variety of short-term memory tasks relative to age-matched control children, but differing patterns of performance. One child showed reduced (or absent) effects of phonological variables, and the other showed reduced effects of semantic variables. A dissociation in their performance on sentence processing tasks was also observed, with one child showing preserved comprehension but impaired repetition, and the other child showing the reverse. The results are consistent with previous findings from brain-damaged adults supporting a multiple-components model of short-term memory in which phonological and semantic components play different roles in sentence processing. Contrary to our initial hypothesis, the phonological component did not appear to play a more important role in sentence comprehension for children than for adults.

We studied the effects of working memory (WM) load on a sentence anomaly task in 12 children (mean age at study = 10.3 years) who had sustained a severe closed-head injury (CHI) at least 10 months previously and 12 healthy children (mean age = 8.92 years). Children were asked to judge whether each sentence (32 anomalous and 32 correct under high and low WM load conditions) was good or not good, and to identify and repair the anomaly. Group and age effects were significant, and both variables interacted with sentence type, reflecting greater sensitivity of anomalous than sensible sentences to CHI and age. A Group × WM load interaction was found. WM deficit contributes to impaired language processing after severe CHI and a metacognitive problem is dissociable from generalized cognitive dysfunction.

Murine adenosine deaminase (ADA) is a ubiquitous purine catabolic enzyme whose expression is subject to developmental and tissue-specific regulation. ADA is enriched in trophoblast cells of the chorioallantoic placenta and is essential for embryonic and fetal development. To begin to understand the genetic pathway controlling Ada gene expression in the placenta, we have identified and characterized a 770-base pair fragment located 5.4 kilobase pairs upstream of the Ada transcription initiation site, which directs reporter gene expression to the placenta of transgenic mice. The expression pattern of the reporter gene reflected that of the endogenous Ada gene in the placenta. Sequence analysis revealed potential binding sites for bHLH and GATA transcription factors. DNase I footprinting defined three protein binding regions, one of which was placenta-specific. Mutations in the potential protein binding sites and footprinting regions resulted in loss of placental expression in transgenic mice. These findings indicate that multiple protein binding motifs are necessary for Ada expression in the placenta.

Brain structures and their white matter connections that may contribute to emotion processing and may be vulnerable to disruption by a traumatic brain injury (TBI) occurring in childhood have not been thoroughly explored.The current investigation examines the relationship between diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA) and apparent diffusion coefficient (ADC), and 3-month post-injury performance on a task of emotion prosody recognition and a control task of phonological discrimination in a group of 91 children who sustained either a moderate-to-severe TBI (n = 45) or orthopaedic injury (OI) (n = 46).Brain-behaviour findings within OI participants confirmed relationships between several significant white matter tracts in emotional prosody performance (i.e. the cingulum bundle, genu of the corpus callosum, inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF). The cingulum and genu were also related to phonological discrimination performance. The TBI group demonstrated few strong brain behaviour relationships, with significant findings emerging only in the cingulum bundle for Emotional Prosody and the genu for Phonological Processing.The lack of clear relationships in the TBI group is discussed in terms of the likely disruption to cortical networks secondary to significant brain injuries.

Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at-risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved alphaII-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI) and normal uninjured controls (age range 12-30 years), and compared them with findings from diffusion tensor magnetic resonance imaging (DTI) and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the uninjured controls. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.

A muscle-specific isoform of adenylosuccinate synthetase (AdSS1, EC) is one of three enzymes that constitute the purine nucleotide cycle, a muscle-specific metabolic cycle. Previously, we showed that the muscle Adss1 gene was highly expressed in both skeletal muscle and heart of the adult mouse. Here we have shown that the Adss1 gene is initially activated early in embryonic development in skeletal muscle and heart precursors and is subsequently up-regulated perinatally. The earliest detectable gene expression corresponds with the establishment of the first myogenic and cardiac lineages. To allow identification of the genetic signals controlling this developmental pattern of expression, the Adss1 gene was cloned and its structure determined. Transgenic analysis has shown that 1.9 kilobase pairs of 5′ flank can activate expression in skeletal muscle progenitors and direct enhanced expression to adult cardiac muscle. Sequence analysis of the promoter and 5′ flanking region revealed the presence of numerous potential muscle-specific cis-regulatory elements.

The objective of this study was to understand how novel psychiatric disorders (NPD) in children with mild traumatic brain injury (MTBI) are related to pre-injury variables, injury-related variables, and concurrent neurocognitive outcome. A group of 79 children, ages 5 to 14 years, who had experienced MTBI, were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline); 60 children were reassessed 12 months post-injury. Standardized instruments were used to assess injury severity; lesion characteristics; pre-injury variables, including psychiatric disorder, family psychiatric history, family functioning, socioeconomic status, psychosocial adversity, adaptive functioning, and post-injury neurocognitive and adaptive functioning. NPD occurred in 17 of 60 participants (28%) in the 6-12-month interval after injury, with disorders that were significantly associated with socioeconomic status, psychosocial adversity, estimated pre-injury academic functioning, and concurrent deficits in adaptive functioning, academic performance, processing speed, memory, and expressive language. NPD was not significantly associated with pre-injury adaptive functioning, injury severity, family psychiatric history, pre-injury psychiatric disorder, lesion location, gender, or age at injury. These findings suggest that the short-term psychiatric morbidity associated with MTBI in children occurs more commonly than previously reported and is related to both pre-injury social factors and concurrent neurocognitive functioning.

The multitude of variables associated with a battery of outcome measures presents a risk for spurious findings in clinical trials and observational studies of mild traumatic brain injury (mTBI). We have used principal components analysis (PCA) to facilitate data reduction by identifying components which represent subsets of neuropsychological measures that are selectively correlated with each other. By merging data from two concurrent mTBI studies using the same outcome measures, we obtained a cohort of 102 mTBI patients and 85 orthopedic injury (OI) comparison patients whom we recruited from 24 hours to 96 hours post-injury and evaluated at one week, 1 month, and 3 months post-injury. Cognitive domains included episodic memory, evaluated by both verbal and visual memory tasks, cognitive processing speed tests, and executive function. Post-concussion and stress-related symptoms were measured by rating scales. PCA identified four components, including cognitive processing speed, verbal memory, visual memory, and a symptom composite representing post-concussion and stress symptoms. mTBI patients older than the mean age of 18 years had slower cognitive processing than the OI patients, but there was no group difference in cognitive processing speed in younger patients. The symptom component score differed significantly as mTBI patients had more severe symptoms than the OI group at each occasion. Our results encourage replication with other cohorts using either the same outcome measures or at least similar domains. PCA is an approach to data reduction that could mitigate spurious findings and increase efficiency in mTBI research.

The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.

OBJECTIVE: : To assess postinjury changes in learning, memory, and metamemory abilities following childhood traumatic brain injury. DESIGN: : Prospective, longitudinal with 5 assessments made from baseline to 24 months postinjury. PARTICIPANTS: : A total of 167 children (aged 5-15 years) with traumatic brain injury (TBI; 64 severe, 55 moderate, and 48 mild). METHODS: : Children completed a judgment of learning task with 4 recall trials and made 3 metamemory judgments. RESULTS: : Relative to those with mild TBI, children with moderate or severe TBI performed worse at earlier times postinjury and had a greater change in performance over time. Performance for moderate and severe groups peaked at 12 months and the performance gap between them and mild TBI group increased slightly from 12 to 24 months. Traumatic brain injury severity did not affect initial study-recall trial performance, but groups did diverge in performance with repeated study. Greater TBI severity was associated with poorer performance on prospective metamemory judgments, but not retrospective judgments. CONCLUSIONS: : Traumatic brain injury severity affected prospective judgments of memory performance and learning strategies, but did not appear to affect either word retention or the forgetting of words over a delay. Implications for rehabilitation are discussed. Language: en