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Find video protocols related to scientific articles indexed in Pubmed.
Sociosexual and communication deficits after traumatic injury to the developing murine brain.
PLoS ONE
PUBLISHED: 08-08-2014
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Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35 injury, suggesting that a longer period of lesion progression or differences in the kinetics of secondary pathogenesis after p21 injury may contribute to observed behavioral differences. Together, these findings indicate vulnerability of the developing brain to social dysfunction, and suggest that a younger age-at-insult results in poorer social and sociosexual outcomes.
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Dimensions of trauma and specific symptoms of complex posttraumatic stress disorder in inner-city youth: a preliminary study.
Violence Vict
PUBLISHED: 05-20-2014
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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.
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Emotional prosody and diffusion tensor imaging in children after traumatic brain injury.
Brain Inj
PUBLISHED: 11-26-2013
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Abstract Primary objective: 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. Research design and methods: 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). Main outcomes and results: 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. Conclusion: 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.
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Psychiatric Disorders in Children and Adolescents Six-to-Twelve Months After Mild Traumatic Brain Injury.
J Neuropsychiatry Clin Neurosci
PUBLISHED: 11-20-2013
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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.
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Preinjury resilience and mood as predictors of early outcome following mild traumatic brain injury.
J. Neurotrauma
PUBLISHED: 11-07-2013
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There is significant heterogeneity in outcomes following mild traumatic brain injury (mTBI). While several host factors (age, gender, and preinjury psychiatric history) have been investigated, the influence of preinjury psychological resilience and mood status in conjunction with mild TBI remains relatively unexplored. Euthymic mood and high resilience are potentially protective against anxiety and postconcussion symptoms, but their relative contributions are currently unknown. This prospective study obtained preinjury estimates of resilience and mood measures in addition to measures of anxiety (Acute Stress Disorder Scale and PTSD-Checklist-Civilian form) and postconcussion symptom severity (Rivermead Post Concussion Symptoms Questionnaire) <24 hours (Baseline), 1 week, and 1 month postinjury in patients with either mTBI (n=46) or a comparison group with orthopedic injuries not involving the head (OI, n=29). The groups did not differ on preinjury resilience or mood status at baseline, but differed significantly on measures of anxiety and postconcussion symptom severity at each subsequent study occasion. Multivariate linear regression analyses were conducted to determine if preinjury resilience and mood were significant contributors to anxiety and postconcussion symptoms during the first month postinjury after accounting for other known host factors (e.g., age at injury, gender, and education). Injury group and preinjury mood status were significant predictors for all three dependent variables at each study occasion (all p<0.007). Preinjury resilience showed a positive trend only for acute stress severity at baseline, but demonstrated significant prediction of all three dependent measures at one week and one month postinjury. These results suggest that preinjury depressed mood and resilience are significant contributors to the severity of postinjury anxiety and postconcussion symptoms, even after accounting for effects of other specific host factors.
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Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study.
Brain Imaging Behav
PUBLISHED: 11-06-2013
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The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographically-comparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALS-related memory impairment, with word-list learning performance relying more upon the integrity of frontal and temporal connections than memory components associated with story recall.
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Neural Activation during Response Inhibition Differentiates Blast from Mechanical Causes of Mild to Moderate Traumatic Brain Injury.
J. Neurotrauma
PUBLISHED: 11-01-2013
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Abstract Military personnel involved in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) commonly experience blast-induced mild to moderate traumatic brain injury (TBI). In this study, we used task-activated functional MRI (fMRI) to determine if blast-related TBI has a differential impact on brain activation in comparison with TBI caused primarily by mechanical forces in civilian settings. Four groups participated: (1) blast-related military TBI (milTBI; n=21); (2) military controls (milCON; n=22); (3) non-blast civilian TBI (civTBI; n=21); and (4) civilian controls (civCON; n=23) with orthopedic injuries. Mild to moderate TBI (MTBI) occurred 1 to 6 years before enrollment. Participants completed the Stop Signal Task (SST), a measure of inhibitory control, while undergoing fMRI. Brain activation was evaluated with 2 (mil, civ)×2 (TBI, CON) analyses of variance, corrected for multiple comparisons. During correct inhibitions, fMRI activation was lower in the TBI than CON subjects in regions commonly associated with inhibitory control and the default mode network. In contrast, inhibitory failures showed significant interaction effects in the bilateral inferior temporal, left superior temporal, caudate, and cerebellar regions. Specifically, the milTBI group demonstrated more activation than the milCON group when failing to inhibit; in contrast, the civTBI group exhibited less activation than the civCON group. Covariance analyses controlling for the effects of education and self-reported psychological symptoms did not alter the brain activation findings. These results indicate that the chronic effects of TBI are associated with abnormal brain activation during successful response inhibition. During failed inhibition, the pattern of activation distinguished military from civilian TBI, suggesting that blast-related TBI has a unique effect on brain function that can be distinguished from TBI resulting from mechanical forces associated with sports or motor vehicle accidents. The implications of these findings for diagnosis and treatment of TBI are discussed.
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Psychiatric disorders in children and adolescents in the first six months after mild traumatic brain injury.
J Neuropsychiatry Clin Neurosci
PUBLISHED: 09-13-2013
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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.
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Centrum semiovale and corpus callosum integrity in relation to information processing speed in patients with severe traumatic brain injury.
J Head Trauma Rehabil
PUBLISHED: 09-10-2013
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This study investigated white matter alterations in the corpus callosum (CC) and centrum semiovale (CSO), using diffusion tensor imaging and magnetization transfer imaging, in participants with severe traumatic brain injury (TBI) and related these changes to processing speed measures.
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Progress in developing common data elements for traumatic brain injury research: version two--the end of the beginning.
J. Neurotrauma
PUBLISHED: 09-09-2013
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To accelerate data sharing and research on traumatic brain injury (TBI), several federal agencies have been collaborating to support the development and implementation of common data elements (CDEs). The first recommendations for CDEs were made in 2010, and were well suited for hospital-based studies of acute TBI in adults. To broaden the utility of the TBI CDEs, experts were asked to update the recommendations to make them relevant to all ages, levels of injury severity, and phases of recovery. The second version of the TBI CDEs (v.2) was organized around four major study types: 1) epidemiological research; 2) studies on acute, hospitalized patients; 3) studies of the rehabilitation for moderate/severe TBI; and 4) mild TBI/concussion research. Given the heterogeneity of TBI, only a small set of core CDEs were found to be relevant across all study types. However, within groups, a much larger set of highly relevant CDEs were identified, and these were called basic CDEs. In addition, an expanded number of supplemental CDEs were specified and recommended for use depending upon the study goals. Version 2 provides a rich data dictionary for TBI research with about 900 CDEs. Many of the CDEs overlap across the study types, which will facilitate comparisons and meta-analysis across studies. Further modifications of the CDEs should be based on evaluation of their usefulness following implementation across a range of studies.
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How functional connectivity between emotion regulation structures can be disrupted: preliminary evidence from adolescents with moderate to severe traumatic brain injury.
J Int Neuropsychol Soc
PUBLISHED: 08-29-2013
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Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.
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The Soft Tissue Immunologic Response to Hydroxyapatite-Coated Transmucosal Implant Surfaces: A Study in Humans.
Clin Implant Dent Relat Res
PUBLISHED: 08-06-2013
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To evaluate the soft tissue response in humans immunologically and histologically after placement of mini-implants coated with or without nano-size hydroxyapatite coatings.
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Neurological outcome scale for traumatic brain injury: III. Criterion-related validity and sensitivity to change in the NABIS hypothermia-II clinical trial.
J. Neurotrauma
PUBLISHED: 08-02-2013
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The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16-45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearmans rank-order correlations were calculated between the NOS-TBI and the glasgow outcome scale (GOS), GOS-extended (GOS-E), disability rating scale (DRS), and neurobehavioral rating scale-revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxons signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.
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Updating memory after mild traumatic brain injury and orthopedic injuries.
J. Neurotrauma
PUBLISHED: 04-18-2013
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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 <1 week (baseline), 1 month, and 3 months after injury. Also included were 58 participants with orthopedic injury (OI) and 27 typically developing (TD) non-injured participants with similar age, socioeconomic status, sex, and ethnicity. MRI data were acquired at baseline and 3 months. Although criteria included a normal CT scan, lesions were detected by MRI in 19 mTBI patients. Participants completed the KeepTrack task, a verbal recall task placing demands on goal maintenance, semantic memory, and memory updating. Scores reflected items recalled and semantic categories maintained. The mTBI group was divided into two groups: high (score ?12) or low (score <12) symptoms based on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Mixed model analyses revealed the trajectory of change in mTBI patients (high and low RPQ), OI patients, and TD subjects were similar over time (although the TD group differed from other groups at baseline), suggesting no recovery from mTBI up to 90 days. For categories maintained, differences in trajectory of recovery were discovered, with the OI comparison group surprisingly performing similar to those in the mTBI group with high RPQ symptoms, and different from low RPQ and the TD groups, bringing up questions about utility of OIs as a comparison group for mTBI. Patients with frontal lesions (on MRI) were also found to perform worse than those without lesions, a pattern that became more pronounced with time.
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Neuropsychological outcome of mTBI: a principal component analysis approach.
J. Neurotrauma
PUBLISHED: 03-04-2013
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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.
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Effects of moderate to severe traumatic brain injury on anticipating consequences of actions in adolescents: a preliminary study.
J Int Neuropsychol Soc
PUBLISHED: 01-14-2013
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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).
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Evidence That the Blood Biomarker SNTF Predicts Brain Imaging Changes and Persistent Cognitive Dysfunction in Mild TBI Patients.
Front Neurol
PUBLISHED: 01-01-2013
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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 ?II-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI), and normal uninjured controls (UCs) (age range 12-30?years), and compared them with findings from diffusion tensor 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 UCs. 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.
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Emerging imaging tools for use with traumatic brain injury research.
J. Neurotrauma
PUBLISHED: 10-17-2011
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This article identifies emerging neuroimaging measures considered by the inter-agency Pediatric Traumatic Brain Injury (TBI) Neuroimaging Workgroup. This article attempts to address some of the potential uses of more advanced forms of imaging in TBI as well as highlight some of the current considerations and unresolved challenges of using them. We summarize emerging elements likely to gain more widespread use in the coming years, because of 1) their utility in diagnosis, prognosis, and understanding the natural course of degeneration or recovery following TBI, and potential for evaluating treatment strategies; 2) the ability of many centers to acquire these data with scanners and equipment that are readily available in existing clinical and research settings; and 3) advances in software that provide more automated, readily available, and cost-effective analysis methods for large scale data image analysis. These include multi-slice CT, volumetric MRI analysis, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), arterial spin tag labeling (ASL), functional MRI (fMRI), including resting state and connectivity MRI, MR spectroscopy (MRS), and hyperpolarization scanning. However, we also include brief introductions to other specialized forms of advanced imaging that currently do require specialized equipment, for example, single photon emission computed tomography (SPECT), positron emission tomography (PET), encephalography (EEG), and magnetoencephalography (MEG)/magnetic source imaging (MSI). Finally, we identify some of the challenges that users of the emerging imaging CDEs may wish to consider, including quality control, performing multi-site and longitudinal imaging studies, and MR scanning in infants and children.
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Decision making after pediatric traumatic brain injury: trajectory of recovery and relationship to age and gender.
Int. J. Dev. Neurosci.
PUBLISHED: 09-23-2011
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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.
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Recommendations for the use of common outcome measures in pediatric traumatic brain injury research.
J. Neurotrauma
PUBLISHED: 08-24-2011
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This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroups recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.
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The relationship of resting cerebral blood flow and brain activation during a social cognition task in adolescents with chronic moderate to severe traumatic brain injury: a preliminary investigation.
Int. J. Dev. Neurosci.
PUBLISHED: 08-06-2011
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Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI.
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Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury.
Soc Neurosci
PUBLISHED: 07-21-2011
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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.
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Diffusion tensor imaging of the perforant pathway zone and its relation to memory function in patients with severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 04-27-2011
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Based on the importance of the perforant pathway (PP) for normal hippocampal function, the vulnerability of temporal structures, and significant memory impairment in patients with traumatic brain injury (TBI), we investigated in vivo changes in the PP zone, hippocampus, and temporal lobe white and gray matter using diffusion tensor imaging (DTI) and volumetric analysis, and any specific relations with memory performance (Verbal Selective Reminding Test, Rey-Osterrieth Complex Figure Test), in 14 patients with severe TBI. Compared to a demographically-similar control group, our patients had significantly decreased fractional anisotropy (FA) and higher apparent diffusion coefficient (ADC) for the PP zone bilaterally, and higher ADC bilaterally in the hippocampus. Volumetric analysis revealed significantly decreased volumes in both hippocampi and temporal gray matter bilaterally. Consistent long-term retrieval (CLTR) and delayed recall were significantly related to (1) right and left PP zone ADC, (2) left hippocampus ADC, and (3) left hippocampal volume. Nonverbal memory (immediate and delayed recall) was significantly associated with (1) right and left PP zone ADC, (2) left hippocampal volume, and (3) gray (immediate recall) and white (immediate recall, bilaterally; delayed recall, left) matter temporal volumes. Advanced neuroimaging analysis can detect in vivo changes in the PP zone and temporal structures in patients with severe TBI, with these changes being highly associated with memory impairment.
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Depression in children and adolescents in the first 6 months after traumatic brain injury.
Int. J. Dev. Neurosci.
PUBLISHED: 04-17-2011
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The objective was to assess the nature, rate, predictive factors, and neuroimaging correlates of novel (new-onset) depressive disorders, both definite and subclinical, after traumatic brain injury (TBI). Children with TBI from consecutive admissions were enrolled and studied with psychiatric interviews soon after injury (baseline), and again 6 months post-injury. Novel definite/subclinical depressive disorders at 6-month follow up occurred in 11% (n=15) of the children and subsets of children with non-anxious depression (n=9) and anxious depression (n=6) were identified. Novel definite/subclinical depressive disorder was significantly associated with older age at the time of injury, family history of anxiety disorder, left inferior frontal gyrus (IFG) lesions, and right frontal white matter lesions. Non-anxious depressions were associated with older age at injury, left IFG and left temporal pole lesions. Anxious depressions were associated with family history of anxiety disorder, Personality Change due to TBI, right frontal white matter lesions, and left parietal lesions. These findings, which are similar to those reported after adult TBI, identify both similarities and differences in non-anxious and anxious depression following childhood TBI with respect to lesion laterality, genetic factors (in the form of family psychiatric history of anxiety disorder), age at injury, and more generalized affective dysregulation.
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Mental state attributions and diffusion tensor imaging after traumatic brain injury in children.
Dev Neuropsychol
PUBLISHED: 04-05-2011
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We studied social cognition in 49 children 3 months after moderate to severe traumatic brain injury (TBI) and in 39 children with orthopedic injury (OI). Children underwent diffusion tensor imaging (DTI) and a mental attribution task showing two triangles. Mental state attributions increased when one triangle reacted to intentions of the other, but less so in the TBI than the OI group. DTI identified injury to white matter microstructure in the TBI group, but the relation of DTI to mental attributions did not differ between groups. Moderate to severe TBI produces white matter disconnections that may affect social cognitive networks.
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Diffusion tensor imaging of incentive effects in prospective memory after pediatric traumatic brain injury.
J. Neurotrauma
PUBLISHED: 03-07-2011
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Few studies exist investigating the brain-behavior relations of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, children with moderate-to-severe TBI performed an EB-PM test with two motivational enhancement conditions and underwent concurrent diffusion tensor imaging (DTI) at 3 months post-injury. Children with orthopedic injuries (OI; n=37) or moderate-to-severe TBI (n=40) were contrasted. Significant group differences were found for fractional anisotropy (FA) and apparent diffusion coefficient for orbitofrontal white matter (WM), cingulum bundles, and uncinate fasciculi. The FA of these WM structures in children with TBI significantly correlated with EB-PM performance in the high, but not the low motivation condition. Regression analyses within the TBI group indicated that the FA of the left cingulum bundle (p=0.003), left orbitofrontal WM (p<0.02), and left (p<0.02) and right (p<0.008) uncinate fasciculi significantly predicted EB-PM performance in the high motivation condition. We infer that the cingulum bundles, orbitofrontal WM, and uncinate fasciculi are important WM structures mediating motivation-based EB-PM responses following moderate-to-severe TBI in children.
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Anxiety disorders in children and adolescents in the first six months after traumatic brain injury.
J Neuropsychiatry Clin Neurosci
PUBLISHED: 02-10-2011
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The studys objective was to assess the nature, rate, predictive factors, and neuroimaging correlates of novel (new-onset) definite anxiety disorders and novel definite/subclinical anxiety disorders (in a broader group of children with at least subclinical anxiety disorders) after traumatic brain injury (TBI). Children with TBI from consecutive admissions to five trauma centers were enrolled and studied with psychiatric interviews soon after injury (baseline) and again 6 months post-injury. Novel definite anxiety disorder and novel definite/subclinical anxiety disorders were heterogeneous and occurred in 8.5% (N=12) and 17% (N=24) of participants, respectively, in the first 6 months after injury. Novel definite anxiety disorder was significantly associated with younger age at injury and tended to be associated with novel depressive disorder, as well as lesions of the superior frontal gyrus. Novel definite/subclinical anxiety disorder was significantly associated with concurrent psychiatric problems of personality change due to TBI and novel definite/subclinical depressive disorder, as well as with lesions of the superior frontal gyrus and a trend-association with frontal lobe white-matter lesions. These findings suggest that anxiety after childhood TBI may be part of a broader problem of affective dysregulation related to damaged dorsal frontal lobe and frontal white-matter systems, with younger children being at greatest risk for developing novel anxiety disorder after TBI.
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Brain imaging correlates of verbal working memory in children following traumatic brain injury.
Int J Psychophysiol
PUBLISHED: 01-24-2011
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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.
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Alterations in white matter pathways in Angelman syndrome.
Dev Med Child Neurol
PUBLISHED: 12-01-2010
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Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity.
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Acute white matter differences in the fornix following mild traumatic brain injury using diffusion tensor imaging.
J Neuroimaging
PUBLISHED: 11-17-2010
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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.
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The temporal stem in traumatic brain injury: preliminary findings.
Brain Imaging Behav
PUBLISHED: 09-14-2010
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The temporal stem (TS) of the temporal lobe is a major white matter (WM) region containing several major pathways that connect the temporal lobe with the rest of the brain. Because of its location, it may be particularly vulnerable to shear-strain effects resulting from traumatic brain injury (TBI). A case vignette is presented in a patient with severe brain injury and focal TS pathology. Also, 12 severe TBI subjects unselected for TS pathology were compared to demographically matched, neurologically-intact controls using diffusion tensor imaging (DTI) to examine white matter tracts associated with the TS, including the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), arcuate fasciculus (AF), cingulum bundle (CB) and the uncinate fasciculus (UF). For each tract, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and compared between the two groups and also examined in relationship to memory performance in the TBI subjects. Significant FA and ADC differences were observed in all tracts in the TBI patients compared to controls, with several relationships with memory outcome noted in the IFOF, ILF and AF. Based on these preliminary findings, the potential role of TBI-induced WM disconnection involving the TS is discussed as well as the relationship of TS damage to neurobehavioral outcome. The need for future studies specifically examining the role of TS injury in TBI is emphasized.
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Effects of traumatic brain injury on a virtual reality social problem solving task and relations to cortical thickness in adolescence.
Neuropsychologia
PUBLISHED: 07-07-2010
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Social problem solving was assessed in 28 youth ages 12-19 years (15 with moderate to severe traumatic brain injury (TBI), 13 uninjured) using a naturalistic, computerized virtual reality (VR) version of the Interpersonal Negotiations Strategy interview (Yeates, Schultz, & Selman, 1991). In each scenario, processing load condition was varied in terms of number of characters and amount of information. Adolescents viewed animated scenarios depicting social conflict in a virtual microworld environment from an avatars viewpoint, and were questioned on four problem solving steps: defining the problem, generating solutions, selecting solutions, and evaluating the likely outcome. Scoring was based on a developmental scale in which responses were judged as impulsive, unilateral, reciprocal, or collaborative, in order of increasing score. Adolescents with TBI were significantly impaired on the summary VR-Social Problem Solving (VR-SPS) score in Condition A (2 speakers, no irrelevant information), p=0.005; in Condition B (2 speakers+irrelevant information), p=0.035; and Condition C (4 speakers+irrelevant information), p=0.008. Effect sizes (Cohens D) were large (A=1.40, B=0.96, C=1.23). Significant group differences were strongest and most consistent for defining the problems and evaluating outcomes. The relation of task performance to cortical thickness of specific brain regions was also explored, with significant relations found with orbitofrontal regions, the frontal pole, the cuneus, and the temporal pole. Results are discussed in the context of specific cognitive and neural mechanisms underlying social problem solving deficits after childhood TBI.
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Diffusion tensor imaging of the cingulum bundle in children after traumatic brain injury.
Dev Neuropsychol
PUBLISHED: 05-07-2010
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Structural damage to the prefrontal-cingulate network has been implicated in cognitive and neurobehavioral deficits associated with traumatic brain injury (TBI). Forty-six children who had sustained moderate-to-severe TBI and 43 children with extracranial injury were imaged using diffusion tensor imaging (DTI). Decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) values were found in the cingulum bundles bilaterally in the TBI group. Cingulum ADC was related to frontal lesion volume, injury severity, and injury mechanism. Finally, cingulum DTI parameters were related to cognitive control measures. DTI detects TBI-related injury to the cingulum, which may facilitate advances in assessment and treatment.
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Patterns of cortical thinning in relation to event-based prospective memory performance three months after moderate to severe traumatic brain injury in children.
Dev Neuropsychol
PUBLISHED: 05-07-2010
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While event-based prospective memory (EB-PM) tasks are a familiar part of daily life for children, currently no data exists concerning the relation between EB-PM performance and brain volumetrics after traumatic brain injury (TBI). This study investigated EB-PM in children (7 to 17 years) with moderate to severe TBI or orthopedic injuries. Participants performed an EB-PM task and concurrently underwent neuroimaging at three months postinjury. Surface reconstruction and cortical thickness analysis were performed using FreeSurfer software. Cortical thickness was significantly correlated with EB-PM (adjusting for age). Significant thinning in the left (dorsolateral and inferior prefrontal cortex, anterior and posterior cingulate, temporal lobe, fusiform, and parahippocampal gyri), and right hemispheres (dorsolateral, inferior, and medial prefrontal cortex, cingulate, and temporal lobe) correlated positively and significantly with EB-PM performance; findings are comparable to those of functional neuroimaging and lesion studies of EB-PM.
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Recommendations for the use of common outcome measures in traumatic brain injury research.
Arch Phys Med Rehabil
PUBLISHED: 04-23-2010
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This article summarizes the selection of outcome measures by the interagency Traumatic Brain Injury (TBI) Outcomes Workgroup to address primary clinical research objectives, including documentation of the natural course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements Workgroups, the TBI Outcomes Workgroup adopted the standard 3-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in TBI from each identified domain, including global level of function, neuropsychological impairment, psychological status, TBI-related symptoms, executive functions, cognitive and physical activity limitations, social role participation, and perceived health-related quality of life. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to some older ("legacy") measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.
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Deficits in analogical reasoning in adolescents with traumatic brain injury.
Front Hum Neurosci
PUBLISHED: 04-19-2010
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Individuals with traumatic brain injury (TBI) exhibit deficits in executive control, which may impact their reasoning abilities. Analogical reasoning requires working memory and inhibitory abilities. In this study, we tested adolescents with moderate to severe TBI and typically developing (TD) controls on a set of picture analogy problems. Three factors were varied: complexity (number of relations in the problems), distraction (distractor item present or absent), and animacy (living or non-living items in the problems). We found that TD adolescents performed significantly better overall than TBI adolescents. There was also an age effect present in the TBI group where older participants performed better than younger ones. This age effect was not observed in the TD group. Performance was affected by complexity and distraction. Further, TBI participants exhibited lower performance with distractors present than TD participants. The reasoning deficits exhibited by the TBI participants were correlated with measures of executive function that required working memory updating, attention, and attentional screening. Using MRI-derived measures of cortical thickness, correlations were carried out between task accuracy and cortical thickness. The TD adolescents showed negative correlations between thickness and task accuracy in frontal and temporal regions consistent with cortical maturation in these regions. This study demonstrates that adolescent TBI results in impairments in analogical reasoning ability. Further, TBI youth have difficulty effectively screening out distraction, which may lead to failures in comprehension of the relations among items in visual scenes. Lastly, TBI youth fail to show robust cortical-behavior correlations as observed in TD individuals.
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Longitudinal changes in the corpus callosum following pediatric traumatic brain injury.
Dev. Neurosci.
PUBLISHED: 03-25-2010
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Atrophy of the corpus callosum (CC) is a documented consequence of moderate-to-severe traumatic brain injury (TBI), which has been expressed as volume loss using quantitative magnetic resonance imaging (MRI). Other advanced imaging modalities such as diffusion tensor imaging (DTI) have also detected white matter microstructural alteration following TBI in the CC. The manner and degree to which macrostructural changes such as volume and microstructural changes develop over time following pediatric TBI, and their relation to a measure of processing speed is the focus of this longitudinal investigation. As such, DTI and volumetric changes in the CC in participants with TBI and a comparison group at approximately 3 and 18 months after injury as well as their relation to processing speed were determined.
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Diffusion tensor imaging analysis of frontal lobes in pediatric traumatic brain injury.
J. Child Neurol.
PUBLISHED: 03-23-2010
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This study examined the use of diffusion tensor imaging in detecting white matter changes in the frontal lobes following pediatric traumatic brain injury. A total of 46 children (ages 8-16 years) with moderate to severe traumatic brain injury and 47 children with orthopedic injury underwent 1.5 Tesla magnetic resonance imaging (MRI) at 3 months postinjury. Conventional MRI studies were obtained along with diffusion tensor imaging. Diffusion tensor imaging metrics, including fractional anisotropy, apparent diffusion coefficient, and radial diffusivity, were compared between the groups. Significant group differences were identified, implicating frontal white matter alterations in the injury group that were predictive of later Glasgow Outcome Scale ratings; however, focal lesions were not related to the Glasgow Outcome Scale ratings. Injury severity was also significantly associated with diffusion tensor imaging metrics. Diffusion tensor imaging holds great promise as an index of white matter integrity in traumatic brain injury and as a potential biomarker reflective of outcome.
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The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and convergent validity.
J. Neurotrauma
PUBLISHED: 03-10-2010
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A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9)
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The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): I. Construct validity.
J. Neurotrauma
PUBLISHED: 03-10-2010
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The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010 ). In the present study we evaluate the measures construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was rho = 0.76, p < 0.0001, suggesting a high degree of correspondence (construct validity) between these two measures of neurological function. Additionally, items from the NOS-TBI compared favorably to the neurological examination items, with correlations ranging from 0.60 to 0.99 (all p < 0.0001). On formal neurological examination, some degree of neurological impairment was observed in every participant in this cohort of individuals undergoing rehabilitation for TBI, and on the NOS-TBI neurological impairment was evident in all but one participant. This study documents the presence of measurable neurological sequelae in a sample of patients with TBI in a post-acute rehabilitation setting, underscoring the need for formal measurement of the frequency and severity of neurological deficits in this population. The results suggest that the NOS-TBI is a valid measure of neurological functioning in patients with TBI.
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Feasibility of the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) in adults.
J. Neurotrauma
PUBLISHED: 03-10-2010
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This article describes the design and initial implementation of the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) as an adaptation of the National Institutes of Health Stroke Scale (NIHSS), specifically for clinical and research use in patients with TBI, including (1) the addition of items specific to TBI, (2) adjustment to the scoring algorithm to allow quantification of deficits in patients who are comatose/vegetative or agitated, and (3) the reassignment of items (i.e., limb ataxia) that are problematic in TBI as supplemental items. The feasibility of using the NOS-TBI is discussed and limitations of the scale are highlighted. This scale offers (1) a cost-effective, brief, practicable, standardized, and quantifiable method of communicating and analyzing neurological deficits in a way that traditional neurological assessment alone cannot currently provide, and (2) a measure that non-physicians can administer. The NOS-TBI may serve a role in clinical practice in patients with TBI similar to the way the NIHSS has functioned for patients following stroke, by serving as a tool for initial stratification of injury severity, and as an outcome measure in clinical trials.
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Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae.
J. Neurotrauma
PUBLISHED: 01-22-2010
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To evaluate the effects of mild to moderate blast-related traumatic brain injury (TBI) on the microstructure of brain white matter (WM) and neurobehavioral outcomes, we studied 37 veterans and service members (mean age 31.5 years, SD = 7.2; post-injury interval 871.5 days; SD = 343.1), whose report of acute neurological status was consistent with sustaining mild to moderate TBI due to blast while serving in Iraq or Afghanistan. Fifteen veterans without a history of TBI or exposure to blast (mean age 31.4 years, SD = 5.4) served as a comparison group, including seven subjects with extracranial injury (post-injury interval 919.5 days, SD = 455.1), and eight who were uninjured. Magnetic resonance imaging disclosed focal lesions in five TBI participants. Post-concussion symptoms (Neurobehavioral Symptom Inventory), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist-Civilian), and global distress and depression (Brief Symptom Inventory) were worse in the TBI participants than the comparison group, but no group differences were found in perceived physical or mental functioning (SF-12). Verbal memory (Selective Reminding) was less efficient in the TBI group, but there were no group differences in nonverbal memory (Selective Reminding) or decision making (Iowa Gambling Task). Verbal memory in the TBI group was unrelated to PTSD severity. Diffusion tensor imaging (DTI) using tractography, standard single-slice region-of-interest measurement, and voxel-based analysis disclosed no group differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, FA of the left and right posterior internal capsule and left corticospinal tract was positively correlated with total words consistently recalled, whereas ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent. Our data do not show WM injury in mild to moderate blast-related TBI in veterans despite their residual symptoms and difficulty in verbal memory. Limitations of the study and implications for future research are also discussed.
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Diffuse damage in pediatric traumatic brain injury: a comparison of automated versus operator-controlled quantification methods.
Neuroimage
PUBLISHED: 01-01-2010
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This investigation had two main objectives: 1) to assess the comparability of volumes determined by operator-controlled image quantification with automated image analysis in evaluating atrophic brain changes related to traumatic brain injury (TBI) in children, and 2) to assess the extent of diffuse structural changes throughout the brain as determined by reduced volume of a brain structure or region of interest (ROI). Operator-controlled methods used ANALYZE software for segmentation and tracing routines of pre-defined brain structures and ROIs. For automated image analyses, the open-access FreeSurfer program was used. Sixteen children with moderate-to-severe TBI were compared to individually matched, typically developing control children and the volumes of 18 brain structures and/or ROIs were compared between the two methods. Both methods detected atrophic changes but differed in the magnitude of the atrophic effect with the best agreement in subcortical structures. The volumes of all brain structures/ROIs were smaller in the TBI group regardless of method used; overall effect size differences were minimal for caudate and putamen but moderate to large for all other measures. This is reflective of the diffuse nature of TBI and its widespread impact on structural brain integrity, indicating that both FreeSurfer and operator-controlled methods can reliably assess cross-sectional volumetric changes in pediatric TBI.
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Diffusion tensor imaging of hemispheric asymmetries in the developing brain.
J Clin Exp Neuropsychol
PUBLISHED: 07-10-2009
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Diffusion tensor imaging (DTI) was performed in 39 right-handed children to examine structural hemispheric differences and the impact of age, socioeconomic status, and sex on these differences. Apparent diffusion coefficient (ADC) values were smaller in the left than in the right temporal, prefrontal, anterior internal capsular and the thalamic regions, and fractional anisotropy (FA) values were larger in the left than in the right internal capsule, thalamus, and cingulate. Significant region-by-sex interactions disclosed that the relation of DTI asymmetries to performance depended on sex including the relation of temporal lobes to reading comprehension and the relation of frontal lobes to solving applied mathematical problems.
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Relationship between neuropsychological outcome and DBS surgical trajectory and electrode location.
J. Neurol. Sci.
PUBLISHED: 06-08-2009
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The outcome literature of subthalamic nuclei (STN) deep brain stimulation (DBS) suggests that cognitive declines are commonly reported following surgery. We hypothesized that differences in electrode position and surgical trajectory may lead to a differential neuropsychological outcome.
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The relation between Glasgow Coma Scale score and later cerebral atrophy in paediatric traumatic brain injury.
Brain Inj
PUBLISHED: 02-12-2009
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To examine initial Glasgow Coma Scale (GCS) score and its relationship with later cerebral atrophy in children with traumatic brain injury (TBI) using Quantitative Magnetic Resonance Imaging (QMRI) at 4 months post-injury. It was hypothesized that a lower GCS score would predict later generalized atrophy. As a guide in assessing paediatric TBI patients, the probability of developing chronic cerebral atrophy was determined based on the initial GCS score.
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Psychiatric disorders after pediatric traumatic brain injury: a prospective, longitudinal, controlled study.
J Neuropsychiatry Clin Neurosci
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The objective was to examine the effects of traumatic brain injury (TBI), as compared with orthopedic injury (OI), relative to the risk for psychiatric disorder. There has only been one previous prospective study of this nature. Participants were age 7-17 years at the time of hospitalization for either TBI (complicated mild-to-severe) or OI. The study used a prospective, longitudinal, controlled design, with standardized psychiatric assessments conducted at baseline (reflecting pre-injury functioning) and 3 months post-injury. Assessments of pre-injury psychiatric, adaptive functioning, family adversity, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales. The outcome measure was the presence of a psychiatric disorder not present before the injury ("novel"), during the first 3 months after TBI. Enrolled participants (N=141) included children with TBI (N=75) and with OI (N=66). The analyses focused on 118 children (84%) (TBI: N=65; OI: N=53) who returned for follow-up assessment at 3 months. Novel psychiatric disorder (NPD) occurred significantly more frequently in the TBI (32/65; 49%) than the OI (7/53; 13%) group. This difference was not accounted for by pre-injury lifetime psychiatric status; pre-injury adaptive functioning; pre-injury family adversity, family psychiatric history, socioeconomic status, injury severity, or age at injury. Furthermore, none of these variables significantly discriminated between children with TBI who developed, versus those who did not develop, NPD. These findings suggest that children with complicated mild-to-severe TBI are at significantly higher risk than OI-controls for the development of NPD in the first 3 months after injury.
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Neuroimaging correlates of novel psychiatric disorders after pediatric traumatic brain injury.
J Am Acad Child Adolesc Psychiatry
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To study magnetic resonance imaging (MRI) correlates of novel (new-onset) psychiatric disorders (NPD) after traumatic brain injury (TBI) and orthopedic injury (OI).
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Pediatric traumatic brain injury: neuroimaging and neurorehabilitation outcome.
NeuroRehabilitation
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Brain injury in the pediatric patient not only occurs in an immature brain, but potentially influences all subsequent brain and neurodevelopmental maturation. This presents unique challenges in neuroimaging the developing central nervous system, which is reviewed herein. The most significant neuroimaging advances in assessing pediatric traumatic brain injury (TBI) have occurred with magnetic resonance imaging (MRI), particularly diffusion tensor imaging and the multiple emerging techniques using functional MRI (fMRI). Pediatric neuroimaging findings of TBI are discussed in terms of techniques that can assess underlying neural networks and provide information about neuroplasticity of recovery. Neuroimaging methods also provide insights into the complexities of brain injury, cognitive and neurobehavioral recovery, and how multimodality contemporary neuroimaging methods best demonstrate underlying neuropathology that affects outcome.
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A primer of neuroimaging analysis in neurorehabilitation outcome research.
NeuroRehabilitation
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Although most neurological patients that enter a rehabilitation treatment program have had either a computed tomography (CT) or magnetic resonance imaging (MRI) scan, the utilization of neuroimaging in rehabilitation has been limited. However, a number of new MRI methods for image analysis hold great promise to better inform the neurorehabilitation clinician. The current review provides a foundation in neuroimaging fundamentals for neurorehabilitation specialists and examines the progress in using such techniques as quantitative MRI analyses, diffusion tensor imaging (DTI) and functional MRI to better understand the neurologically impaired patient.
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Neuroimaging in neurorehabilitation.
NeuroRehabilitation
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Tremendous advances in neuroimaging methods and analytic techniques hold great promise in providing the rehabilitation clinician with a much greater understanding of brain pathology and its potential influence on rehabilitation outcome. This special issues of NeuroRehabilitation overviews the field. Contemporary neuroimaging methods are reviewed specifically in traumatic brain injury (TBI), anoxic brain injury (ABI) and stroke. Innovative methods combined with standard quantitative metrics and traditional clinical assessment provide the rehabilitation clinician with multiple methods to best understand the nature and extent on underlying neuropathology and how to use this information in guiding rehabilitation therapies and predicting outcome.
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Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials.
J. Neurosurg.
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The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes.
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Serial measurement of memory and diffusion tensor imaging changes within the first week following uncomplicated mild traumatic brain injury.
Brain Imaging Behav
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Patients (n = 8) with uncomplicated mild traumatic brain injury (mTBI) underwent serial assessments (4) with diffusion tensor imaging (DTI) and neuropsychological testing within the first 8 days post-injury. Using a multi-case study design, we examined changes in brain parenchyma (via DTI-derived fractional anisotropy [FA], apparent diffusion coefficient [ADC], axial diffusivity [AD] and radial diffusivity [RD] in the left cingulum bundle) and in memory performance (via Hopkins Verbal Learning Test-Revised). Qualitative inspection of the results indicated that memory performance was transiently affected in most participants over the course of the week, with performance most negatively impacted on the second assessment (days 3-4 or 97-144 h post-injury), and then returning to within normal limits by 8 days post-injury. Alternatively, FA and other DTI metrics showed a more complex pattern, with the trajectory of some participants changing more prominently than others. For example, FA transiently increased in some participants over the study period, but the pattern was heterogeneous. Memory performance appeared to mirror changes in FA in certain cases, supporting a pathophysiological basis to memory impairment following mTBI. However, the pattern and the degree of symmetry between FA and memory performance was complex and did not always correspond. Serial imaging over the semi-acute recovery period may be important in reconciling conflicting findings in mTBI utilizing memory and/or DTI. Serial use of imaging modalities including DTI may aid understanding of underlying pathophysiological changes in the semi-acute post-injury period. Should a consistent pattern emerge that allows identification of patients at-risk for acute and/or persistent symptoms, such knowledge could guide development of therapeutic targets in mTBI and in understanding the most effective administration time window for these agents.
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Diffusion tensor imaging in moderate-to-severe pediatric traumatic brain injury: changes within an 18 month post-injury interval.
Brain Imaging Behav
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Traumatic brain injury (TBI) is a leading cause of death and disability in children, yet little is known regarding the pattern of TBI-related microstructural change and its impact on subsequent development. Diffusion tensor imaging (DTI) was used to examine between-group differences at two time points (planned intervals of 3 months and 18 months post-injury) and within-group longitudinal change in a group of children and adolescents aged 7-17 years with moderate-to-severe TBI (n?=?20) and a comparison group of children with orthopedic injury (OI) (n?=?21). In the 3- and 18-month cross-sectional analyses, tract-based spatial statistics (TBSS) generally revealed decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) in the TBI group in regions of frontal, temporal, parietal, and occipital white matter as well as several deep subcortical structures, though areas of FA decrease were more prominent at the 3-month assessment, and areas of ADC increase were more prominent at the 18 month assessment, particularly in the frontal regions. In terms of the within-group changes over time, the OI group demonstrated primarily diffuse increases in FA over time, consistent with previous findings of DTI-measured white matter developmental change. The TBI group demonstrated primarily regions of FA decrease and ADC increase over time, consistent with presumed continued degenerative change, though regions of ADC decrease were also appreciated. These results suggest that TBI-related microstructural changes are dynamic in children and continue until at least 18 months post-injury. Understanding the course of these changes in DTI metrics may be important in TBI for facilitating advances in management and intervention.
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Diffusion tensor imaging and volumetric analysis of the ventral striatum in adults with traumatic brain injury.
Brain Inj
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The aim was to determine if there are changes in the integrity and volume of the ventral striatum following severe traumatic brain injury (TBI) and if these changes relate to executive functioning.
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Longitudinal changes in cortical thickness in children after traumatic brain injury and their relation to behavioral regulation and emotional control.
Int. J. Dev. Neurosci.
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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.
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Patterns of Early Emotional and Neuropsychological Sequelae following Mild Traumatic Brain Injury.
J. Neurotrauma
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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 one week or less postinjury 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 following injury in adolescents and adults ages 12-30 years with mTBI (n=73) compared to orthopedically-injured (OI, n=65) and typically-developing controls (TDC, n=40). The mTBI group reported significantly greater general psychological distress, postconcussion symptom severity, and posttraumatic stress severity than OI (all p<.0001) and TDC (all p<.0001); the OI and TDC groups responded similarly on these variables. There was a significant Group×Age interaction on the Total score (p<.009), and the Cognitive (p=.01) and Somatic (p<.032) subscales of the Rivermead Post Concussion Symptoms Questionnaire where increasing symptom severity was associated with increasing age in the mTBI group. On neuropsychological assessment, the mTBI group performed significantly more poorly compared to OI for Verbal Selective Reminding Test (delayed recall, p=.0003) and Symbol-Digit Modalities Test (SDMT written p=.03; oral, p=.001). The TDC group more robustly outperformed the mTBI group on these measures and also on the Brief Visuospatial Memory Test (delayed recall, p<.04), Letter Fluency (p<.02), and Category Switching (p<.04). The TDC group outperformed the OI group on SDMT and Letter Fluency. These findings are consistent with previous reports of acute deficits in episodic memory and processing speed acutely after mTBI. Notably, however, these data also demonstrate the challenges of comparison group selection since differences were also found between the TDC and OI groups.
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Serial Atlas-based DTI Study of Uncomplicated Mild Traumatic Brain Injury in Adults.
J. Neurotrauma
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In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our goal was to characterize regional and global macrostructural and microstructural attributes of white matter (WM), gray matter (GM) in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata, corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. The normalized volume percentages of global CSF, GM and WM were not different between the mTBI and orthopedic comparison (OC) groups at either the baseline or follow-up time point or between the baseline and follow-up time points within the OC group (p>0.17; uncorrected for multiple comparisons). The DTI metrics did not differ between groups at either occasion. However, an increase was noted on follow-up in OC group in the global MD of GM (uncorrected p=0.003) and WM (uncorrected p=0.02), indicating a decrease in diffusivity at the 3 month post-injury as compared to the baseline scan. An analysis of the DTI data collected longitudinally in the corona radiata (CR) show insignificant changes in the OC group (p>0.08; N=37). The CR radial diffusivity was found to be elevated in the between group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data which is uncorrected for multiple comparisons demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the corona radiata.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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