Diffusion tensor imaging and volumetric analysis of the ventral striatum in adults with traumatic brain injury.

OBJECTIVES: 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. METHODS: This study recruited 14 participants with severe TBI (mean age: 22 years) and 15 demographically-matched controls. All participants underwent magnetic resonance imaging with diffusion tensor imaging (DTI) and volumetric analysis at 6 months post-injury. Participants with TBI underwent neuropsychological testing and the relation between imaging data and cognitive performance was examined. RESULTS: Differences in DTI parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) were found between participants with TBI and controls. Correlations between right and left ventral striatum ADC and the executive functioning factor of the Neurobehavioural Rating Scale-Revised (NRS-R) were found. Correlations between right ventral striatum FA and the Controlled Oral Word Association Test, Trails Making Test Part B (TMT-B) time and NRS-R executive functioning factor were also found. Volumetric analysis showed a difference only in left nucleus accumbens between TBI and control groups. CONCLUSIONS: The integrity of the ventral striatum is affected following severe TBI. Decreases in executive functioning are related to damage to the ventral striatum and its associated structures.

Alterations in white matter pathways in Angelman syndrome.

AIM: 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. METHOD: DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour. RESULTS: The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p < 0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p < 0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p < 0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p < 0.05). INTERPRETATION: Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning.

Longitudinal changes in the corpus callosum following pediatric traumatic brain injury.

BACKGROUND: 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. METHODS: Forty-eight children and adolescents aged 7-17 years who sustained either complicated mild or moderate-to-severe TBI (n = 23) or orthopedic injury (OI; n = 25) were studied. The participants underwent brain MRI and were administered the Eriksen flanker task at both time points. RESULTS: At 3 months after injury, there were significant group differences in DTI metrics in the total CC and its subregions (genu/anterior, body/central and splenium/posterior), with the TBI group demonstrating significantly lower fractional anisotropy (FA) and a higher apparent diffusion coefficient (ADC) in comparison to the OI group. These group differences were also present at 18 months after injury in all CC subregions, with lower FA and a higher ADC in the TBI group. In terms of longitudinal changes in DTI, despite the group difference in mean FA, both groups generally demonstrated a modest increase in FA over time though this increase was only significant in the splenium/posterior subregion. Interestingly, the TBI group also generally demonstrated ADC increases from 3 to 18 months though the OI group demonstrated ADC decreases over time. Volumetrically, the group differences at 3 months were marginal for the midanterior and body/central subregions and total CC. However, by 18 months, the TBI group demonstrated a significantly decreased volume in all subregions except the splenium/posterior area relative to the OI group. Unlike the OI group, which showed a significant volume increase in subregions of the CC over time, the TBI group demonstrated a significant and consistent volume decrease. Performance on a measure of processing speed did not differentiate the groups at either visit, and only the OI group showed significantly improved performance over time. Processing speed was related to FA in the splenium/posterior and total CC only in the TBI group on both occasions, with a stronger relation at 18 months. CONCLUSION: In response to TBI, macrostructural volume loss in the CC occurred over time; yet, at the microstructural level, DTI demonstrated both indicators of continued maturation and development even in the damaged CC, as well as evidence of potential degenerative change. Unlike volumetrics, which likely reflects the degree of overall neuronal loss and axonal damage, DTI may reflect some aspects of postinjury maturation and adaptation in white matter following TBI. Multimodality imaging studies may be important to further understand the long-term consequences of pediatric TBI.

The relation between Glasgow Coma Scale score and later cerebral atrophy in paediatric traumatic brain injury.

PRIMARY OBJECTIVE: 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. METHODS AND PROCEDURES: The probability model used data from 45 paediatric patients (mean age = 13.6) with mild-to-severe TBI and 41 paediatric (mean age = 12.4) orthopaedically-injured children. RESULTS: This study found a 24% increase in the odds of developing an abnormal ventricle-to-brain ratio (VBR) and a 27% increase in the odds of developing reduced white matter percentage on neuroimaging with each numerical drop in GCS score. Logistic regression models with cut-offs determined by normative QMRI data confirmed that a lower initial GCS score predicts later atrophy. CONCLUSION: GCS is a commonly used measure of injury severity. It has proven to be a prognostic indicator of cognitive recovery and functional outcome and is also predictive of later parenchymal change.

Correlates of social problem solving during the first year after traumatic brain injury in children.

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

Diffusion tensor imaging in relation to cognitive and functional outcome of traumatic brain injury in children.

OBJECTIVE: To investigate the relation of white matter integrity using diffusion tensor imaging (DTI) to cognitive and functional outcome of moderate to severe traumatic brain injury (TBI) in children. DESIGN: Prospective observational study of children who had sustained moderate to severe TBI and a comparison group of children who had sustained orthopedic injury (OI). PARTICIPANTS: Thirty-two children who had sustained moderate to severe TBI and 36 children with OI were studied. METHODS: Fiber tracking analysis of DTI acquired at 3-month postinjury and assessment of global outcome and cognitive function within 2 weeks of brain imaging. Global outcome was assessed using the Glasgow Outcome Scale and the Flanker task was used to measure cognitive processing speed and resistance to interference. RESULTS: Fractional anisotropy and apparent diffusion coefficient values differentiated the groups and both cognitive and functional outcome measures were related to the DTI findings. Dissociations were present wherein the relation of Fractional anisotropy to cognitive performance differed between the TBI and OI groups. A DTI composite measure of white matter integrity was related to global outcome in the children with TBI. CONCLUSIONS: DTI is sensitive to white matter injury at 3 months following moderate to severe TBI in children, including brain regions that appear normal on conventional magnetic resonance imaging. DTI measures reflecting diffusion of water parallel and perpendicular to white matter tracts as calculated by fiber tracking analysis are related to global outcome, cognitive processing speed, and speed of resolving interference in children with moderate to severe TBI. Longitudinal data are needed to determine whether these relations between DTI and neurobehavioral outcome of TBI in children persist at longer follow-up intervals.

Acute white matter differences in the fornix following mild traumatic brain injury using diffusion tensor imaging.

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.

Neuroimaging correlates of novel psychiatric disorders after pediatric traumatic brain injury.

OBJECTIVE: To study magnetic resonance imaging (MRI) correlates of novel (new-onset) psychiatric disorders (NPD) after traumatic brain injury (TBI) and orthopedic injury (OI). METHOD: Participants were 7 to 17 years of age at the time of hospitalization for either TBI or OI. The study used a prospective, longitudinal, controlled design with standardized psychiatric assessments conducted at baseline (reflecting pre-injury function) and 3 months post-injury. MRI assessments including diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), volumetric measures of gray and white matter regions, volumetric measures of lesions, and cortical thickness were conducted. Injury severity was assessed by standard clinical scales. The outcome measure was the presence of an NPD identified during the first 3 months after injury. RESULTS: There were 88 participants (TBI, 44; OI, 44). NPD occurred more frequently in the TBI (21/44; 48%) versus the OI (6/44; 14%) group (Fisher's exact test, p = .001). NPD in TBI participants was not related to injury severity. Multivariate analysis of covariance of the relationship between FA in hypothesized regions of interest (bilateral frontal and temporal lobes, bilateral centrum semiovale, bilateral uncinate fasciculi) and NPD and group (TBI versus OI) was significant, and both variables (NPD, p < .05; group, p < .001) were jointly significantly related to FA. NPD was not significantly related to volumetric measures of white or gray matter structures, volumetric measures of lesions, or cortical thickness measures. CONCLUSIONS: Lowered white matter integrity may be more important in the pathophysiology of NPD than indices of gray matter or white matter atrophic changes, macroscopic lesions, and injury severity.

Mental state attributions and diffusion tensor imaging after traumatic brain injury in children.

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.

Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury.

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.

Brain imaging correlates of verbal working memory in children following traumatic brain injury.

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.

Diffusion tensor imaging of incentive effects in prospective memory after pediatric traumatic brain injury.

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.

Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae.

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.

Diffusion tensor imaging analysis of frontal lobes in pediatric traumatic brain injury.

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.

Evaluating the relationship between memory functioning and cingulum bundles in acute mild traumatic brain injury using diffusion tensor imaging.

Compromised memory functioning is one of the commonly reported cognitive sequelae seen following mild traumatic brain injury (mTBI). Diffusion tensor imaging (DTI) has been shown to be sufficiently sensitive at detecting early microstructural pathological alterations after mTBI. Given its location and shape, the cingulate, which is comprised of the cingulate gyrus (gray matter) and cingulum bundles (white matter), is selectively vulnerable to mTBI. In this study we examined the integrity of cingulum bundles using DTI, and the relationship between cingulum bundles and memory functioning. Twelve adolescents with mTBI and 11 demographically-matched healthy controls were studied. All participants with mTBI had a Glasgow Coma Scale score of 15, and were without intracranial findings on CT scan. Brain scans were performed on average 2.92 days post-injury, and all participants were administered the Verbal Selective Reminding Test (VSRT), an episodic verbal learning and memory task. Participants with mTBI had a significantly lower apparent diffusion coefficient (ADC) bilaterally than controls (p < 0.001). Despite the marginal significance of the group difference in fractional anisotropy (FA), the effect size between groups was moderate (d = 0.66). Cognitively, healthy controls performed better than the TBI group on immediate and delayed recall; however, the difference did not reach statistical significance. In the mTBI group, FA of the left cingulum bundle was significantly correlated with 30-min delayed recall (r = -0.56, p = 0.05). A marginally significant correlation was found between ADC of the left cingulum bundle and the total words of immediate recall (r = 0.59, p = 0.07). No significant correlation was found between DTI metrics and memory functioning for the control group. These preliminary findings indicate that cingulate injury likely contributes to the cognitive sequelae seen during the early phase post-mTBI.

The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and convergent validity.

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)

The temporal stem in traumatic brain injury: preliminary findings.

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.

Diffusion tensor imaging of the cingulum bundle in children after traumatic brain injury.

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.

Diffusion tensor imaging of hemispheric asymmetries in the developing brain.

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.