Verbal working memory impairments following traumatic brain injury: an fNIRS investigation

The construct of working memory and its reliance on dorsolateral prefrontal cortex (DLPFC) have been the focus of many studies in healthy subjects and in clinical populations. However, transfer of knowledge gained from cognitive science studies to clinical applications can be a challenging goal. This scarce cross-dissemination may be partially due to the use of ‘tools’ that are limited in their ability to generate meaningful information about impairments in clinical groups. To this end, this paper investigates the use of functional near-infrared spectroscopy (fNIRS), which offers unique opportunities for recording neuroactivation. Specifically, we examine measures of the DLPFC hemodynamic response during a working memory task in adults with traumatic brain injury (TBI) and healthy controls. Analysis of hemodynamic measures showed significant differences between the two groups, even without differences in behavioral performance. Additional subtle disparities were linked to levels of performance in TBI and healthy subjects. fNIRS hemodynamic measures may therefore provide novel information to existing theories and knowledge of the working memory construct. Future studies may further define these subtle differences captured by fNIRS to help identify which components affect inter-individual variations in performance and could play a contributing role in the choice and planning of neurorehabilitation interventions targeting working memory.     

White matter correlates of different aspects of facial affect recognition impairment following traumatic brain injury

Although facial affect recognition deficits are well documented in individuals with moderate-to-severe traumatic brain injury (TBI), little research has examined the neural mechanisms underlying these impairments. Here, we use diffusion tensor imaging (DTI), specifically the scalars fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD), to examine relationships between regional white-matter integrity and two facial affect sub-skills: perceptual affect recognition abilities (measured by an affect matching task) and verbal categorization of facial affect (measured by an affect labeling task). Our results showed that, within the TBI group, higher levels of white-matter integrity in tracts involved in affect recognition (inferior fronto-occipital, inferior longitudinal, and uncinate fasciculi) were associated with better performance on both tasks. Verbal categorization skills were specifically and positively correlated with integrity of the left uncinate fasciculus. Moreover, we observed a striking lateralization effect, with perceptual abilities having an almost exclusive relationship with integrity of right hemisphere tracts, while verbal abilities were associated with both left and right hemisphere integrity. The findings advance our understanding of the neurobiological mechanisms that underlie subcomponents of facial affect recognition and lead to different patterns of facial affect recognition impairment in adults with TBI.     

Predicting premorbid neuropsychological functioning following pediatric traumatic brain injury

Abstract

This study examined the prediction of premorbid neuropsychological functioning using data from an ongoing prospective study of traumatic brain injuries (TBI) in children ages 6 to 12 years. Prediction equations were derived based on 80 children with orthopedic injuries (OI), who served as a comparison group for the children with TBI. Collectively, parent ratings of premorbid school performance, maternal ethnicity, family socioeconomic status, and children's word recognition skill predicted from 13% to 45% of the variance in three measures of neuropsychological functioning. The regression equations were used to compute predicted scores among 109 children with TBI. Actual scores fell significantly below predicted scores among children with TBI, and the magnitude of the deficits was correlated with injury severity. Premorbid neuropsychological functioning can be predicted in children with TBI, but with less precision than would be desirable for clinical purposes.     

Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An A‐CAP study

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8–16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children''s pre‐injury and 1‐month post‐injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion‐weighted imaging at post‐acute (2–33 days post‐injury) and chronic (3 or 6 months via random assignment) post‐injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, −0.58 (−1.04, −0.11), and superior longitudinal fasciculus, −0.49 (−0.90, −0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post‐injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.     

Diffusion tensor imaging changes following mild,moderate and severe adult traumatic brain injury: a meta-analysis

Diffusion tensor imaging quantifies the asymmetry (fractional anisotropy; FA) and amount of water diffusion (mean diffusivity/apparent diffusion coefficient; MD/ADC) and has been used to assess white matter damage following traumatic brain injury (TBI). In healthy brains, diffusion is constrained by the organization of axons, resulting in high FA and low MD/ADC. Following a TBI, diffusion may be altered; however the exact nature of these changes has yet to be determined. A meta-analysis was therefore conducted to determine the location and extent of changes in DTI following adult TBI. The data from 44 studies that compared the FA and/or MD/ADC data from TBI and Control participants in different regions of interest (ROIs) were analyzed. The impact of injury severity, post-injury interval (acute: ≤ 1 week, subacute: 1 week-3 months, chronic: > 3 months), scanner details and acquisition parameters were investigated in subgroup analyses, with the findings indicating that mild TBI should be examined separately to that of moderate to severe injuries. Lower FA values were found in 88% of brain regions following mild TBI and 92% following moderate-severe TBI, compared to Controls. MD/ADC was higher in 95% and 100% of brain regions following mild and moderate-severe TBI, respectively. Moderate to severe TBI resulted in larger changes in FA and MD/ADC than mild TBI. Overall, changes to FA and MD/ADC were widespread, reflecting more symmetric and a higher amount of diffusion, indicative of white matter damage.     

Assessing gait impairment following experimental traumatic brain injury in mice

Although gait disturbance is frequently documented among patients with traumatic brain injury (TBI), gait data from animal models of TBI are lacking. To determine the effect of TBI on gait function in adult mice, we assessed gait changes following unilateral controlled cortical impact (CCI) using a computer-assisted automated gait analysis system. Three days after CCI, intensity, area or width of paw contact were significantly decreased in forepaw(s) while the relative paw placement between the fore and hindpaws altered, suggesting that TBI affected sensorimotor status and reduced interlimb coordination. Similar to TBI patients, CCI decreased gait velocity and stride length, and prolonged stance and swing phase in mice. Following CCI, step pattern was also changed with increasing use in the ipsilateral-diagonal limb sequence. Our results indicate that gait analysis provides great insight into both spatial and temporal aspects of limb function changes during overground locomotion in quadruped species with head injury that are valuable for the purpose of treatment and rehabilitation. Our study also provides additional functional validation for the established mouse CCI model that is relevant to human head injury.     

Motor and cognitive function evaluation following experimental traumatic brain injury

Traumatic brain injury (TBI) in humans may cause extensive sensorimotor and cognitive dysfunction. As a result, many TBI researchers are beginning to assess behavioral correlates of histologically determined damage in animal models. Although this is an important step in TBI research, there is a need for standardization between laboratories. The ability to reliably test treatments across laboratories and multiple injury models will close the gap between treatment success in the lab and success in the clinic. The goal of this review is to describe and evaluate the tests employed to assess functional outcome after TBI and to overview aspects of cognitive, sensory, and motor function that may be suitable targets for therapeutic intervention.     

Short- and long-term social outcomes following pediatric traumatic brain injury.

The social outcomes of pediatric traumatic brain injury (TBI) were examined in a prospective, longitudinal study that included 53 children with severe TBI, 56 with moderate TBI, and 80 with orthopedic injuries, recruited between 6 and 12 years of age. Child and family functioning were assessed at baseline, at 6- and 12-month follow-ups, and at an extended follow-up a mean of 4 years post injury. Growth curve analyses revealed that pediatric TBI yields negative social outcomes that are exacerbated by family environments characterized by lower socioeconomic status, fewer family resources, and poorer family functioning. After controlling for group membership, age, race, socioeconomic status, and IQ, path analyses indicated that long-term social outcomes were accounted for in part by specific neurocognitive skills, including executive functions and pragmatic language, and by social problem-solving. Deficits in these domains among children with TBI are likely to reflect damage to a network of brain regions that have been implicated in social cognition.     

Neuroanatomic correlates of CVLT-C performance following pediatric traumatic brain injury.

Traumatic brain injury (TBI) frequently results in memory problems, and the degree of memory impairment is related to injury severity and is commonly associated with lesions in frontal and temporal brain areas. This study examined the relationship among injury severity, brain lesions, and memory in children with moderate to severe TBI using Donders' (1999) 5-factor model of performance on the California Verbal Learning Test-Children's Version (CVLT-C). Seventy-six children underwent magnetic resonance imaging (MRI) scans 3 months post-TBI and testing 1 year post-TBI. Results showed injury severity (Glasgow Coma Scale) was not predictive of performance on 4 of the 5 factors. Volume of frontal and/or temporal brain lesions was significantly predictive of performance on 3 of the 5 factors. Unexpectedly, lesion volume outside these areas (extra-frontotemporal) was predictive of performance on all 5 factors. In contrast, Verbal IQ at 1 year was most strongly associated with preinjury factors (socioeconomic status and special education involvement), although extra-frontotemporal lesions also contributed to the variability in this measure. Results suggest that in children with moderate to severe TBI, extra-frontal/temporal lesions are predictive of memory outcome 1 year postinjury above and beyond initial severity or frontal/temporal contusions. This finding may relate to widespread diffuse axonal injury, which potentially disconnects brain circuits mediating memory following moderate to severe TBI.     

Mood and anxiety disorders following pediatric traumatic brain injury: a prospective study

Studies utilizing standardized instruments for assessing mood and/or anxiety disorders following pediatric traumatic brain injury have seldom been reported in the literature. Previous reports have largely focused on cognitive impairment, behavioral dysfunction, or adaptive functioning, and have typically relied on parental informants. In this study, children hospitalized for mild (N = 42) and moderate/severe (N = 19) brain injury were assessed 6-months postinjury using the Anxiety disorders Module A and the Mood disorders Module C of the Diagnostic Interview Schedule for Children - IV Revision (DISC-IV). The data collected for the brain injury groups were compared to an orthopedic control group (N = 35). The relationship between a new onset mood and/or anxiety disorder (NOD) and injury severity indices was examined. Sequential logistical regression was also utilized to examine the impact of a brain injury, demographic variables, preinjury psychiatric disturbance, development disorders, litigation status and postinjury environmental stress on emotional outcome. Results indicated a relationship between brain injury and NOD. Multivariate analysis demonstrated that postinjury level of stress and severity of brain injury were the most robust predictors of NOD, accounting for 23% of the variance in the model. These results support the premise that the development of a mood and/or anxiety disorder following pediatric head injury is mediated by multiple determinants. The findings suggest that early psychosocial assessment and interventions aimed at increasing a child's coping may attenuate the emotional consequences of pediatric brain injury.     

Presynaptic excitability changes following traumatic brain injury in the rat

Pathological processes affecting presynaptic terminals may contribute to morbidity following traumatic brain injury (TBI). Posttraumatic widespread neuronal depolarization and elevated extracellular potassium and glutamate are predicted to alter the transduction of action potentials in terminals into reliable synaptic transmission and postsynaptic excitation. Evoked responses to orthodromic single- and paired-pulse stimulation were examined in the CA1 dendritic region of hippocampal slices removed from adult rats following fluid percussion TBI. The mean duration of the extracellularly recorded presynaptic volley (PV) increased from 1.08 msec in controls to 1.54 msec in slices prepared at 1 hr postinjury. There was a time-dependent recovery of this injury effect, and PV durations at 2 and 7 days postinjury were not different from controls. In slices removed at 1 hr postinjury, the initial slopes of field excitatory postsynaptic potentials (fEPSPs) were reduced to 36% of control values, and input/output plots revealed posttraumatic deficits in the transfer of excitation from pre- to postsynaptic elements. Manipulating potassium currents with 1.0 mM tetraethylammonium or elevating potassium ion concentration to 7.5 mM altered evoked responses but did not replicate the injury effects to PV duration. Paired-pulse facilitation of fEPSP slopes was significantly elevated at all postinjury survivals: 1 hr, 2 days, and 7 days. These results suggest two pathological processes with differing time courses: 1) a transient impairment of presynaptic terminal functioning affecting PV durations and the transduction of afferent activity in the terminals to reliable synaptic excitation and 2) a more protracted deficit to the plasticity mechanisms underlying paired-pulse facilitation.     

Irritability following traumatic brain injury

This study was undertaken to identify the clinical and pathoanatomical correlates of irritability in patients with closed head injuries. A consecutive series of 66 patients was assessed in hospital and at 3, 6, 9, and 12-month follow-ups. Patients fulfilling criteria for irritability were divided into 2 groups based on the immediate or delayed onset of their irritability and compared with patients without irritability for background characteristics, impairment variables, and lesion characteristics. There were 12 patients (18.2%) with acute onset irritability and 10 (15.1%) with delayed onset irritability. Acute onset irritability patients had a higher frequency of left cortical lesions. Delayed onset irritability patients showed a strong association with poor social functioning and greater impairment in activities of daily living. The findings suggest that post-brain injury irritability may have different causes and treatment in the acute and chronic stages.     

Psychosis following traumatic brain injury

Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.     

A brief report on MRI investigation of experimental traumatic brain injury

Traumatic brain injury is a major cause of death and disability. This is a brief report based on a symposium presentation to the2014 Chinese Neurotrauma Association Meeting in San Francisco, USA. It covers the work from our laboratory in applying multimodal MRI to study experimental traumatic brain injury in rats with comparisons made to behavioral tests and histology. MRI protocols include structural, perfusion, manganese-enhanced, diffusion-tensor MRI, and MRI of blood-brain barrier integrity and cerebrovascular reactivity.     

Psychosis following traumatic brain injury

Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.