Deficits In Traumatic Brain Injury Research Articles

Treating Traumatic Brain Injury with Exercise: Onset Delay and Previous Training as Key Factors Determining its Efficacy

Purpose Exercise reduces cognitive deficits in traumatic brain injury (TBI), but early post-trauma exercise is often discouraged due to potential harm. The purpose was to evaluate the interaction between pre- and post-injury physical exercise on cognition, neuronal survival and inflammation. Methods Rats were either sham-operated and kept sedentary (Sham) or subjected to controlled cortical impact injury and then distributed into sedentary (Tbi), pre-injury exercise (Pre-Tbi), post-injury exercise with early (24 hours, Tbi-early) or late (6 days, Tbi-late) onset, and a combination of pre- and post-injury exercise with early (Pre-Tbi-early) or late (Pre-Tbi-late) onset. Object recognition memory, hippocampal volume, neuronal survival (NeuN+) in the hippocampus and perirhinal cortex, and microglial activity (Iba-1) in the hippocampus were evaluated. Results All exercise conditions, except TBI-early, attenuated the significant memory impairment at 24-hour retention caused by TBI. Additionally, Pre-TBI-early treatment led to memory improvement at 3-hour retention. Pre-TBI reduced neuronal death and microglial activation in the hippocampus. TBI-late, but not TBI-early, mitigated hippocampal volume loss, loss of mature neurons in the hippocampus, and inflammation. Combining pre-injury and early-onset exercise reduced memory deficits but did not affect neuronal death or microglial activation. Combining pre-injury and late-onset exercise had a similar memory-enhancing effect than late post-injury treatment alone, albeit with reduced effects on neuronal density and neuroinflammation. Conclusions Pre-TBI physical exercise reduces the necessary onset delay of post-TBI exercise to obtain cognitive benefits, yet the exact mechanisms underlying this reduction require further research.

Aerobic exercise and cognitive function in chronic severe traumatic brain injury survivors: a within-subject A-B-A intervention study

BackgroundFollowing acute and sub-acute rehabilitation from severe traumatic brain injury (TBI), minimal to no efficacious interventions to treat ongoing cognitive deficits are available. Aerobic exercise is a non-invasive behavioral intervention with promise to treat cognitive deficits in TBI populations.MethodsSix individuals, aged 24–62 years, with chronic (> 8 months since injury) severe (Glasgow Coma Scale of 3–8) TBI were recruited from two outpatient rehabilitation centers. In an A-B-A study design, 20-weeks of supervised aerobic exercise interventions were delivered three times per week (phase B) in addition to participants typical rehabilitation schedules (phases A). The effect of phase B was tested on a trail making test part B (primary outcome measure of executive function) as well as objective daily physical activity (PA), using both group level (linear mixed effect models) and single subject statistics.ResultsFive of six participants increased trail-making test part B by more than 10% pre-to-post phase B, with three of six making a clinically meaningful improvement (+ 1SD in normative scores). A significant main effect of time was seen with significant improvement in trail-making test part B pre-to-post exercise (phase B). No significant effects in other planned comparisons were found. Statistically significant increases in daily moderate-to-vigorous PA were also seen during phase B compared to phase A with three of six individuals making a significant behaviour change.ConclusionsThe addition of supervised aerobic exercise to typical rehabilitation strategies in chronic survivors of severe TBI can improve executive set shifting abilities and increase voluntary daily PA levels.Trial registrationRetrospective trial registration on July 11 2024 with trial number: ISRCTN17487462.

Identifying neural correlates of balance impairment in traumatic brain injury using partial least squares correlation analysis

Objective.Balance impairment is one of the most debilitating consequences of traumatic brain injury (TBI). To study the neurophysiological underpinnings of balance impairment, the brain functional connectivity during perturbation tasks can provide new insights. To better characterize the association between the task-relevant functional connectivity and the degree of balance deficits in TBI, the analysis needs to be performed on the data stratified based on the balance impairment. However, such stratification is not straightforward, and it warrants a data-driven approach.Approach.We conducted a study to assess the balance control using a computerized posturography platform in 17 individuals with TBI and 15 age-matched healthy controls. We stratified the TBI participants into balance-impaired and non-impaired TBI usingk-means clustering of either center of pressure (COP) displacement during a balance perturbation task or Berg Balance Scale score as a functional outcome measure. We analyzed brain functional connectivity using the imaginary part of coherence across different cortical regions in various frequency bands. These connectivity features are then studied using the mean-centered partial least squares correlation analysis, which is a multivariate statistical framework with the advantage of handling more features than the number of samples, thus making it suitable for a small-sample study.Main results.Based on the nonparametric significance testing using permutation and bootstrap procedure, we noticed that the weakened theta-band connectivity strength in the following regions of interest significantly contributed to distinguishing balance impaired from non-impaired population, regardless of the type of stratification:left middle frontal gyrus, right paracentral lobule, precuneus, andbilateral middle occipital gyri. Significance.Identifying neural regions linked to balance impairment enhances our understanding of TBI-related balance dysfunction and could inform new treatment strategies. Future work will explore the impact of balance platform training on sensorimotor and visuomotor connectivity.

Bypassing Striatal Learning Mechanisms Using Delayed Feedback to Circumvent Learning Deficits in Traumatic Brain Injury.

Feedback facilitates learning by guiding and modifying behaviors through an action-outcome contingency. As the majority of existing studies have focused on the immediate presentation of feedback, the impact of delayed feedback on learning is understudied. Prior work demonstrated that learning from immediate and delayed feedback employed distinct brain regions in healthy individuals, and compared to healthy individuals, individuals with traumatic brain injury (TBI) are impaired in learning from immediate feedback. The goal of the current investigation was to assess the effects of delayed vs immediate feedback on learning in individuals with TBI and examine brain networks associated with delayed and immediate feedback processing. Nonprofit research organization. Twenty-eight individuals with moderate-to-severe TBI. Participants completed a paired-associate word learning task while undergoing magnetic resonance imaging. During the task, feedback was presented either immediately, after a delay, or not at all (control condition). Learning performance accuracy, confidence ratings, post-task questionnaire, and blood oxygen level-dependent signal. Behavioral data showed that delayed feedback resulted in better learning performance than immediate feedback and no feedback. In addition, participants reported higher confidence in their performance during delayed feedback trials. During delayed vs immediate feedback processing, greater activation was observed in the superior parietal and angular gyrus. Activation in these areas has been previously associated with successful retrieval and greater memory confidence. The observed results might be explained by delayed feedback processing circumventing the striatal dopaminergic regions responsible for learning from immediate feedback that are impaired in TBI. In addition, delayed feedback evokes less of an affective reaction than immediate feedback, which likely benefited memory performance. Indeed, compared to delayed feedback, positive or negative immediate feedback was more likely to be rated as rewarding or punishing, respectively. The findings have significant implications for TBI rehabilitation and suggest that delaying feedback during rehabilitation might recruit brain regions that lead to better functional outcomes.

Virtual Reality Assessment of Attention Deficits in Traumatic Brain Injury: Effectiveness and Ecological Validity

Early detection is crucial for addressing attention deficits commonly associated with Traumatic brain injury (TBI), informing effective rehabilitation planning and intervention. While traditional neuropsychological assessments have been conventionally used to evaluate attention deficits, their limited ecological validity presents notable challenges. This study explores the efficacy and validity of a novel virtual reality test, the Computerized Battery for the Assessment of Attention Disorders (CBAAD), among a cohort of TBI survivors (n = 20), in comparison to a healthy control group (n = 20). Participants, ranging in age from 21 to 62 years, were administered a comprehensive neuropsychological assessment, including the CBAAD and the Attention Related Cognitive Errors Scale. While variations in attentional performance were observed across age cohorts, the study found no statistically significant age-related effects within either group. The CBAAD demonstrated sensitivity to attentional dysfunction in the TBI group, establishing its value as a comprehensive test battery for assessing attention in this specific population. Regression analyses demonstrated the CBAAD’s effectiveness in predicting real-life attentional errors reported by TBI patients. In summary, the CBAAD demonstrates sensitivity to attentional dysfunction in TBI patients and the ability to predict real-world attentional errors, establishing its value as a comprehensive test battery for assessing attention in this specific population. Its implementation holds promise for enhancing the early identification of attentional impairments and facilitating tailored rehabilitation strategies for TBI patients.

Anacardic acid improves neurological deficits in traumatic brain injury by anti-ferroptosis and anti-inflammation

BackgroundTraumatic brain injury (TBI) is an important cause of disability and death. TBI leads to multiple forms of nerve cell death including ferroptosis due to iron-dependent lipid peroxidation. Anacardic acid (AA) is a natural component extracted from cashew nut shells, which has been reported to have neuroprotective effects in traumatic brain injury. We investigated whether AA has an anti-ferroptosis effect in TBI. MethodsWe used the Feeney free-fall impact method to construct a TBI model to investigate the effect of AA on ferroptosis caused by TBI, in which Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, served as a positive control group. We first identified the therapeutic effect of AA on TBI through modified neurological severity score (mNSS) and determined the appropriate concentration. Secondly, we investigated the effect of AA on the expression level of the key protein of ferroptosis by Western blotting and immunohistochemistry. Then the effect of AA on nerve tissue injury and nerve function improvement was verified. Finally, enzym-linked immunosorbent assay (ELISA) was used to verify that AA could reduce inflammation after TBI. ResultsWe found the intensely inhibitory effect of AA on ferroptosis, which is in parallel with the results obtained after Fer-1 treatment. In addition, AA and Fer-1 mitigated TBI-mediated tissue defects, destruction of the blood-brain barrier, and neurodegeneration. Novel object recognition (NOR), mNSS and water maze test showed that AA could significantly reduce the impairment of neural function and behavioral cognitive ability caused by TBI. Finally, we also demonstrated that AA has not only an anti-ferroptosis effect, but also an anti-inflammation effect. ConclusionsAA can reduce the neurological impairment and behavioral cognitive impairment caused by TBI through the dual effect of anti-ferroptosis and anti-inflammation.

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales.

Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary's Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George's Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients' performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary's Hospital TBI clinic in London (UK). The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r=0.86, p<0.001 and r=0.81, p=0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555)=3.99; p<0.001). Online cognitive assessment of TBI patients is feasible, sensitive, and efficient. When combined with normative sociodemographic models and autogenerated reports, it has the potential to transform cognitive assessment in the healthcare setting. This work was funded by a National Institute for Health Research (NIHR) Invention for Innovation (i4i) grant awarded to DJS and AH (II-LB-0715-20006).

Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING/IRE1α pathway after traumatic brain injury in mice.

Increased neutrophil extracellular trap (NET) formation has been reported to be associated with cerebrovascular dysfunction and neurological deficits in traumatic brain injury (TBI). However, the biological function and underlying mechanisms of NETs in TBI-induced neuronal cell death are not yet fully understood. First, brain tissue and peripheral blood samples of TBI patients were collected, and NETs infiltration in TBI patients was detected by immunofluorescence staining and Western blot. Then, a controlled cortical impact device was used to model brain trauma in mice, and Anti-Ly6G, DNase, and CL-amidine were given to reduce the formation of neutrophilic or NETs in TBI mice to evaluate neuronal death and neurological function. Finally, the pathway changes of neuronal pyroptosis induced by NETs after TBI were investigated by administration of peptidylarginine deiminase 4 (a key enzyme of NET formation) adenovirus and inositol-requiring enzyme-1 alpha (IRE1α) inhibitors in TBI mice. We detected that both peripheral circulating biomarkers of NETs and local NETs infiltration in the brain tissue were significantly increased and had positive correlations with worse intracranial pressure (ICP) and neurological dysfunction in TBI patients. Furthermore, the depletion of neutrophils effectively reduced the formation of NET in mice subjected to TBI. we found that degradation of NETs or inhibition of NET formation significantly inhibited nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 1 (NLRP1) inflammasome-mediated neuronal pyroptosis after TBI, whereas these inhibitory effects were abolished by cyclic GMP-AMP (cGAMP), an activator of stimulating Interferon genes (STING). Moreover, overexpression of PAD4 in the cortex by adenoviruses could aggravate NLRP1-mediated neuronal pyroptosis and neurological deficits after TBI, whereas these pro-pyroptotic effects were rescued in mice also receiving STING antagonists. Finally, IRE1α activation was significantly upregulated after TBI, and NET formation or STING activation was found to promote this process. Notably, IRE1α inhibitor administration significantly abrogated NETs-induced NLRP1 inflammasome-mediated neuronal pyroptosis in TBI mice. Our findings indicated that NETs could contribute to TBI-induced neurological deficits and neuronal death by promoting NLRP1-mediated neuronal pyroptosis. Suppression of the STING/ IRE1α signaling pathway can ameliorate NETs-induced neuronal pyroptotic death after TBI.

Word Learning as a Window to Memory and Rehabilitation Outcomes in Traumatic Brain Injury.

The purpose of this viewpoint is to advocate for increased study of word learning abilities and word learning interventions in traumatic brain injury (TBI). We describe the word learning process and the unique opportunities afforded by studying each component and stage. Building on discussions at the 2022 International Cognitive-Communication Disorders Conference, we describe how word learning may underlie a variety of functional outcomes after TBI, making it a promising target for rehabilitation. Finally, we discuss principles that may guide study in this critical area to advance outcomes after TBI for children and adults. Word learning is a dynamic and iterative process taking place over time and in multiple stages. Thus, studying word learning affords the opportunity to parse the relative contributions of multiple memory systems to different phases and components of the process. However, single-timepoint designs are insufficient to capture the full word learning process, which occurs over time and across contexts. Word learning also presents an opportunity to assess the contributions of behavioral and lifestyle factors (e.g., sleep and exercise) to different memory phases. Understanding these interactions could drive clinical interventions aimed at improving memory through manipulable external behaviors. Word learning is key to success in functional spheres across the life span. The importance of words to daily life remains after TBI, even as the memory systems that support word learning are disrupted. The empirical study of word learning and rehabilitation of word learning deficits in TBI presents a promising new direction in understanding the breadth of neurogenic cognitive-communication disorders and an opportunity to explore a potential driver of functional outcome and impactful rehabilitation target.

Astrocyte-derived CCL7 promotes microglia-mediated inflammation following traumatic brain injury

Microglia are immune cells of the central nervous system that mediate neuroinflammation. It is widely known that microglia-mediated inflammation in the brain contribute to the widespread tissue damage and neurological deficits in traumatic brain injury (TBI). However, the mechanisms responsible for this inflammatory response remain elusive. Here, we investigated the role of astrocyte-derived chemokine (C-C motif) ligand 7 (CCL7) in microglial-controlled inflammation following TBI. Our results demonstrated that astrocyte-derived CCL7 induced microglial activation and the release of proinflammatory mediators in the cortex and serum of rats that underwent experimental TBI. Furthermore, CCL7 knockout improved microglia-controlled inflammation, brain morphology and neurological dysfunction following TBI. In vitro, CCL7-siRNA attenuated the LPS-induced expression of pro-inflammatory markers in the co-culture of microglia and astrocytes. Collectively, our findings uncover an important role for astrocyte-derived CCL7 in promoting microglia-mediated inflammation after TBI and suggests CCL7 could serve as a potential therapeutic strategy for attenuating TBI by inhibiting microglial activation.

N-Adamantyl Phthalimidine: A New Thalidomide-like Drug That Lacks Cereblon Binding and Mitigates Neuronal and Synaptic Loss, Neuroinflammation, and Behavioral Deficits in Traumatic Brain Injury and LPS Challenge.

Neuroinflammation contributes to delayed secondary cell death following traumatic brain injury (TBI), has the potential to chronically exacerbate the initial insult, and represents a therapeutic target that has largely failed to translate into human efficacy. Thalidomide-like drugs have effectively mitigated neuroinflammation across cellular and animal models of TBI and neurodegeneration but are complicated by adverse actions in humans. We hence developed N-adamantyl phthalimidine (NAP) as a new thalidomide-like drug to mitigate inflammation without binding to cereblon, a key target associated with the antiproliferative, antiangiogenic, and teratogenic actions seen in this drug class. We utilized a phenotypic drug discovery approach that employed multiple cellular and animal models and ultimately examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) TBI in mice. NAP mitigated LPS-induced inflammation across cellular and rodent models and reduced oligomeric α-synuclein and amyloid-β mediated inflammation. Following CCI TBI, NAP mitigated neuronal and synaptic loss, neuroinflammation, and behavioral deficits, and is unencumbered by cereblon binding, a key protein underpinning the teratogenic and adverse actions of thalidomide-like drugs in humans. In summary, NAP represents a new class of thalidomide-like drugs with anti-inflammatory actions for promising efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.

Combined Memory Training: An Approach for Episodic Memory Deficits in Traumatic Brain Injury.

Purpose The study aimed to test a combination of semantic memory and traditional episodic memory therapies on episodic memory deficits in adults with traumatic brain injury. Method Twenty-five participants who had been diagnosed with traumatic brain injury and had episodic memory deficits were randomly assigned either to a combined memory treatment group (n = 16) or to a wait-list control group (n = 9). Before and after treatment, they completed standardized neuropsychological testing for episodic memory and related cognitive domains, including the California Verbal Learning Test-Second Edition, the Controlled Oral Word Association Test, the University of Southern California Repeatable Episodic Memory Test, the Wechsler Abbreviated Scale of Intelligence-Second Edition Matrices, the Test of Everyday Attention, the Memory Assessment Clinics Self-Rating Scale, the Expressive Vocabulary Test-Second Edition, and the Story Recall subtest from the Rivermead Behavioural Memory Test. In addition to a traditional episodic memory therapy, the treatment group received a novel semantic memory-focused therapy, which involved participants finding meaningful connections between diverse concepts represented by sets of two or three words. Results The treatment group demonstrated statistically significant improvement in memory for list learning tasks, and there was a significant difference from pretest to posttest between the treatment group and the wait-list control group. Clinical significance was demonstrated for the treatment group using minimally important difference calculations. Conclusion Combined memory therapy resulted in significant improvements in episodic memory, semantic memory, and attention, in comparison to no treatment. Supplemental Material https://doi.org/10.23641/asha.14049968.

A-122 Intra-Individual Variability in Traumatic Brain Injury and Questionable Performance Validity

Abstract Objective Intra-individual variability (IIV) has been associated with cognitive dysfunction and traumatic brain injury (TBI) severity. This study examined IIV in physical medicine and rehabilitation patients grouped by TBI severity and performance validity. Method Participants (N = 213) were 32% female and 90% white with average age and education of 42 (SD = 13) and 14 (SD = 2) years, respectively. Participants completed an outpatient evaluation using a flexible battery of up to 33 common neuropsychological measures. Participants were grouped by TBI severity and validity: mild (32%), moderate (14%), severe (32%), and questionable performance validity (QPV; 22%). QPV was determined on the basis of embedded and freestanding validity measures. Test battery scores were converted to T scores. Cases with four or more scores below 36 T were identified as impaired. Measures of IIV were calculated including overall test battery mean (OTBM), test battery standard deviation (SD), kurtosis, skew, range, and unbiased coefficient of variation (UCV). IIV measures were compared across groups. Results Groups were significantly different in OTBM (p &amp;lt; .001), kurtosis (p &amp;lt; .03), and UCV (p &amp;lt; .001). In valid cases, TBI severity was associated with OTBM (rho = −.31), SD (.19), kurtosis (−.16), and UCV (.33). Impaired and unimpaired cases were significantly different in OTBM (p &amp;lt; .001), SD (p &amp;lt; .001), range (p &amp;lt; .01), and UCV (p &amp;lt; .001). QPV cases were similar to impaired cases on measures of IIV. Conclusions IIV measures have potential clinical utility in characterizing cognitive deficits in TBI and warrant further study.

Apolipoprotein E promotes white matter remodeling via the Dab1‐dependent pathway after traumatic brain injury

IntroductionAxonal injury results in long‐term neurological deficits in traumatic brain injury (TBI) patients. Apolipoprotein E (ApoE) has been reported to activate intracellular adaptor protein Disabled‐1 (Dab1) phosphorylation via its interaction with ApoE receptors. The Dab1 pathway acts as a regulator of axonal outgrowth and growth cone formation in the brain.AimsWe hypothesized that ApoE may alleviate axonal injury and regulate axonal regeneration via the Dab1 pathway after TBI.ResultsIn this study, we established a model of controlled cortical impact (CCI) to mimic TBI in vivo. Using diffusion tensor imaging to detect white matter integrity, we demonstrated that APOE‐deficient mice exhibited lower fractional anisotropy (FA) values than APOE+/+ mice at 28 days after injury. The expression levels of axonal regeneration and synapse plasticity biomarkers, including growth‐associated protein 43 (GAP43), postsynaptic density protein 95 (PSD‐95), and synaptophysin, were also lower in APOE‐deficient mice. In contrast, APOE deficiency exerted no effects on the levels of myelin basic protein (MBP) expression, oligodendrocyte number, or oligodendrocyte precursor cell number. Neurological severity score (NSS) and behavioral measurements in the rotarod, Morris water maze, and Y maze tests revealed that APOE deficiency caused worse neurological deficits in CCI mice. Furthermore, Dab1 activation downregulation by the ApoE receptor inhibitor receptor‐associated protein (RAP) or Dab1 shRNA lentivirus attenuated the beneficial effects of ApoE on FA values, GAP43, PSD‐95, and synaptophysin expression, and neurological function tests. Additionally, the effects of ApoE on axonal regeneration were further validated in vitro. In a mechanical scratch injury model of primary cultured neurons, recombinant ApoE protein treatment enhanced axonal outgrowth and growth cone formation in injured neurons; however, these effects were attenuated by Dab1 shRNA, consistent with the in vivo results.ConclusionCollectively, these data suggest that ApoE promotes axonal regeneration partially through the Dab1 pathway, thereby contributing to functional recovery following TBI.

Theory of Mind Impairments Highlighted With an Ecological Performance-Based Test Indicate Behavioral Executive Deficits in Traumatic Brain Injury.

Background: In view of the recent literature, the negative impact of traumatic brain injury (TBI) on social cognition remains a debated issue. On one hand, a considerable number of studies reported significant impairments in emotion recognition, empathy, moral reasoning, social problem solving, and mentalizing or theory of mind (ToM) abilities in patients with TBI. On the other hand, the ecological validity of social cognition tasks is still a matter of concern and debate for clinicians and researchers.Objectives: The objectives of the present study were 2-fold: (1) to assess social cognition in TBI with an ecological performance-based test which focuses on ToM ability, and (2) to study the relationship between performances on this task and behavioral disorders. To this end, 47 patients with moderate to severe TBI in the chronic stage were assessed with a ToM task, the Movie for the Assessment of Social Cognition (MASC), a film displaying social interactions in natural settings and asking for an evaluation of the emotions, thoughts, and intentions of the characters. Behavioral disorders were assessed with the Behavioral Dysexecutive Syndrome Inventory (BDSI), a structured interview of an informant in assessing changes compared with previous behavior in 12 domains.Results: Patients were significantly less accurate in mental state attribution than a demographically matched group of 38 healthy control subjects. Significant others of patients also reported more behavioral executive problems than controls' relatives on most of the domains of the BDSI. In addition, social cognition performance in the MASC was significantly correlated with behavioral dysexecutive problems rated by proxies on the BDSI.Conclusions: This study is the first to find association between impairments in mentalizing abilities in the MASC and behavioral impairments in patients with TBI, confirming the added value of this ecological task and that the recognition of social signals is a key element for adequate behavioral functioning.

Top-Down vs. Bottom-Up: A Case Series in Verbal Working Memory Treatments for Chronic Traumatic Brain Injury Deficits

Purpose Individuals with traumatic brain injury may suffer chronic cognitive–linguistic deficits in areas such as verbal working memory, which impede attainment of long-term rehabilitation goals. The purpose of this study was to determine whether individual rehabilitation programs focusing on cognitive skill building of memory and attention in the verbal domain may provide comparable outcomes to traditional compensatory, mnemonics-based training approaches. Method Rhythmic language training is presented as a novel therapeutic tool for targeting discrete cognitive skills that may provide specific benefits for chronic traumatic brain injury symptoms that conventional therapy programs may not. Standardized testing with the California Verbal Learning Test–Second Edition ( Delis, Kramer, Kaplan, &amp; Ober, 2000 ) was used for pre- and posttest comparisons in 2 cases presented as a series. Electroencephalography was employed concurrently with behavioral testing to examine changes in working memory for each case. Results Posttest measurements indicated positive changes in verbal working memory occurred, but to different degrees for each participant. Conclusion The preliminary positive effects observed in standardized testing for the experimental method of rhythmic language training warrant further investigation for potential clinical applications.

Community Integration in Traumatic Brain Injury: The Contributing Factor of Affect Recognition Deficits.

Individuals with traumatic brain injury (TBI) can experience social isolation, which is damaging to well-being and counterproductive to successful rehabilitation. It has been proposed that social cognitive deficits that commonly result from TBI may contribute to weakened social integration. However, the consequences of specific social cognitive deficits in TBI are still being delineated. The current work sought to better characterize the relationship between community integration and facial affect recognition (FAR) in TBI. A total of 27 participants with moderate to severe TBI and 30 healthy controls (HCs) completed two tests of FAR, which employed either static photographic stimuli or dynamic video stimuli (The Awareness of Social Inference Test). The Community Integration Questionnaire was also administered to participants. Participants with TBI were significantly impaired on both the static and dynamic FAR measures, yet the deficits were most pronounced within the dynamic task. Furthermore, participants with TBI reported lower community integration compared with HCs. FAR was positively associated with community integration in both groups, such that participants with proficient affect recognition skills were better integrated into their communities. FAR deficits may contribute to the lack of community integration often observed in TBI; thus, interventions designed to improve FAR may be beneficial to this population's ability to successfully reintegrate into society.

A comparison of laboratory, clinical, and self-report measures of prospective memory in healthy adults and individuals with brain injury

ABSTRACTIndividuals with traumatic brain injury (TBI) have demonstrated deficits in prospective memory (PM) functioning when compared to healthy adults. These deficits have been measured using laboratory measures, clinical measures, and self-report questionnaires. However, PM has been shown to involve multiple cognitive processes and have a variety of stages. Thus, it is not known whether these measures all assess the same aspects of PM. Thus, this study was designed to measure the convergent validity of the three types of PM measures in both healthy adults and individuals with TBI. We aimed to investigate the convergent validity of the three types of tasks in two ways. First, we sought to investigate whether the PM deficits experienced by people with TBI are consistent across tasks. Second, we sought to examine the relationship between the three types of tasks. Results demonstrated that while all three types of measures were sensitive to PM deficits in TBI, there were differences in the aspects/processes of PM being measured. Data from the laboratory measure suggested a specific difficulty with detecting the correct cue. Data from the clinical measure suggested that TBI has a greater effect on time-based cues than event-based cues and that the primary deficit is a prospective intention retrieval deficit rather than the retrospective memory component. In addition, those with TBI did not differ from healthy adults when the time delay was short enough, suggesting that PM is not universally impaired. Data from the self-report questionnaire suggested that those with TBI are more sensitive to difficulties with basic activities of daily living rather than instrumental activities on daily living. These results are discussed in terms of rehabilitation techniques that could focus first on cue detection and use basic activities of daily living as outcome measures.

Psychological traits predict impaired awareness of deficits independently of neuropsychological factors in chronic traumatic brain injury.

To dissociate injury-related factors from psychological contributions to impaired awareness of deficits following traumatic brain injury (TBI); impaired awareness is theorized to partly reflect psychological factors (e.g., denial), but empirical evidence for this theory is scarce. We examined how different factors predict awareness in patients undergoing rehabilitation (N=43). Factors included (1) neurological (injury severity), (2) neuropsychological loss, (3) psychological (denial, projection, identification), and (4) personality (narcissism). The Patient Competency Rating Scale, comparing patient with clinician reports on different functional domains; the Thematic Apperception Test, an injury-independent measure of the propensity to mobilize specific defence mechanisms; and the Narcissism Personality Inventory. Impaired awareness was not predicted by injury-related and neuropsychological scores but was significantly predicted by use of primitive defence mechanisms (denial and projection). Patients who underestimate their abilities also demonstrated high denial levels, but contrary to underestimators, this was positively related to depression and negatively to awareness. Primitive defence mechanism use significantly contributes to impaired awareness independent of injury-related factors, particularly in domains associated with self-identity. Well-validated tests of defence mechanism mobilization are needed to support clinical interpretation of and intervention with impaired awareness. More research is needed to understand the psychology of hypersensitivity to deficits. This study provides an empirical demonstration of dissociable contributions of neurological and psychological factors to awareness of deficits in TBI. Trait proclivity to mobilize defence mechanisms in response to anxiety-provoking situations can be measured, and strongly predicts impaired awareness. Importantly, measures of psychological reactions were independent of responses to the neurological deficits themselves, discriminating between psychological and neurological contributions to impaired awareness. The importance of identifying psychological reactions to impaired awareness and hindering rehabilitation success is highlighted, and vital for clinicians to consider during the rehabilitation process. Psychological reactions to TBI can be identified using well-validated, quantitative measures of the use of psychological defences (e.g., Cramer's Thematic Apperception Test scoring system), and the authors suggest this is a critical step to properly characterize and manage awareness in patients during treatment. Although only TBI patients were examined, the results may inform impaired awareness that occur as a result of other disorders and illnesses. The patients in this study were in the chronic stages of the injury, and therefore, the results may not generalize to patients in more acute stages.

Abnormal connectivity in the sensorimotor network predicts attention deficits in traumatic brain injury

The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p < 10−3) and a trend towards a significant effect of the DMN connectivity on attention (p = 0.058). A group-by-network interaction on attention was found in the sensorimotor network (p = 0.002). In TBI, attention was positively related to abnormal connectivity within the sensorimotor RSN, while in HC this relation was negative. Our results show altered patterns of functional connectivity after TBI. Attention impairments in TBI were associated with increased connectivity in the sensorimotor network. Further research is needed to test whether attention in TBI patients is directly affected by changes in functional connectivity in the sensorimotor network or whether the effect is actually driven by changes in the DMN.