Traumatic Brain Injury Impairment Research Articles

Memory for Conversation in Traumatic Brain Injury: A Feasibility Study and Preliminary Findings.

Despite common clinical complaints about memory for conversation after traumatic brain injury (TBI), the nature and severity of this deficit are unknown. In this research note, we report feasibility and preliminary data from a new conversation memory study protocol. Participants in this feasibility study were 10 pairs, each including an adult with chronic, moderate-to-severe TBI and their chosen familiar conversation partner. The experiment began with a naturalistic conversation between participants with TBI and their conversation partners. After a filled delay, participants next completed verbal recall for the conversation, which we transcribed and coded for their accuracy relative to the original conversation. Participants also read chosen statements from their original conversation and predicted what each partner would remember in a week. One week later, participants completed a posttest about who said each of the chosen statements, allowing direct comparison to their predictions. We successfully collected conversation memory data from all 10 pairs, suggesting that this protocol is feasible for future study. In this preliminary sample, people with TBI and their conversation partners did not differ in the accuracy of their recall for the conversation about 20 min after it occurred. When asked to predict their partner's delayed memory, conversation partners were less accurate than participants with TBI because they underestimated how much their partners with TBI would remember. Measuring memory for conversation in TBI is feasible and may advance the characterization of cognitive-communication impairment in TBI, and its heterogeneity, in everyday contexts. https://doi.org/10.23641/asha.25927513.

Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury

BackgroundThe gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway.MethodsIn this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing.ResultsP. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris’s water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements.ConclusionsWe demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.

Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway.

Oxidative stress (OS) and inflammatory reactions play pivotal roles in secondary brain injury after traumatic brain injury (TBI). Histone deacetylase 3 (HDAC3) controls the acetylation of histones and non-histones, which has a significant impact on the central nervous system's reaction to damage. This research determined the implications of RGFP966, a new and specific inhibitor of HDAC3, for the antioxidant (AO) systems mediated by nuclear factor erythroid2-related factor 2 (Nrf2) and the Nod-like receptor protein 3 (NLRP3) inflammasome in TBI. The study also studied the underlying mechanisms of RGFP966's actions. Our objective was to examine the impacts and underlying RGFP966 mechanisms in TBI. In vitro, a rat cortical neuron OS model was induced by H2O2, followed by the addition of RGFP966 to the culture medium. Neurons were collected after 24h for western blot (WB), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 2'-7'-dichlorodihydrofluorescein diacetate staining. In vivo, RGFP966 (10mg/kg) was administered post-TBI. Brain tissue water content and modified neurological severity scores were assessed 72h post-injury. Cortical tissues surrounding the focal injury were subjected to western blot, TUNEL staining, Nissl staining and immunofluorescence/immunohistochemistry staining, and malondialdehyde level, hindered glutathione content and superoxide dismutase activity were measured. Serum was collected for the enzyme-linked immunosorbent assay. Nrf2-specific shRNA lentivirus was injected into the lateral ventricle of rats for 7days, and cerebral cortex tissue was analyzed by WB and real-time polymerase chain reaction. During in vitro and in vivo experiments, RGFP966 suppressed HDAC3 expression, promoted Nrf2 nuclear translocation, activated downstream AO enzymes, mitigated excessive reactive oxygen species production and alleviated nerve cell apoptosis. RGFP966 effectively reduced brain edema and histological damage and enhanced neurological and cognitive function in rats with TBI. RGFP966 markedly inhibited NLRP3 inflammasome activation mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4). Nrf2 knockdown in TBI rats attenuated the AO and anti-inflammatory, neuroprotective impacts of RGFP966. Overall, our findings demonstrate that RGFP966 can mitigate the first brain damage and neurological impairments in TBI. The underlying mechanism involves triggering the Nrf2-mediated AO system and negatively regulating the HMGB1/TLR4-mediated NLRP3 inflammasome pathway.

Reactive oxygen species-responsive HET0016 prodrug-loaded liposomes attenuate neuroinflammation and improve neurological deficit in a rat model of juvenile traumatic brain injury.

The arachidonic acid pathway metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemia/reperfusion brain injury. Inhibition of 20-HETE formation can protect the developing brain from global ischemia. In previous studies, we have found that treatment with the 20-HETE synthesis inhibitor N-hydroxy-N-4-butyl-2-methylphenylformamidine (HET0016) can protect the immature brain from traumatic brain injury (TBI), but its hydrophobic nature limits its full potential. We designed a reactive oxygen species-responsive HET0016 prodrug, which consists of a thioketal link between HET0016 and stearyl alcohol (HET-TK-SA), and used the nanoprodrug strategy to successfully synthesize liposomes HET0016 prodrug liposomes (HPLs) to facilitate the application of HET0016 in protection from TBI. HPLs demonstrated spherical shape, size of about 127.8 nm, a zeta potential of -28.8 mv, a narrow particle size distribution and good stability. Male rats at postnatal day 16-17 underwent controlled cortical impact (CCI) followed by intravenous injection with vehicle or HET0016 (1 mg/kg, 2 h post-injury, once/day for 3 days). The results of the in vivo demonstrated that HPLs has good biosafety and can pass through the blood-brain barrier. Not only that compared with HET0016, HPLs better-inhibited inflammation and improved neuronal degeneration, which further led to lesion volume reduction, upgraded behavioral task performance, and ameliorated the degree of TBI impairment. Our results demonstrated HPLs could be a new strategy for juvenile TBI therapy.

Gamma frequency entrainment rescues cognitive impairment by decreasing postsynaptic transmission after traumatic brain injury.

The relationship between oscillatory activity in hippocampus and cognitive impairment in traumatic brain injury (TBI) remains unclear. Although TBI decreases gamma oscillations and 40 Hz light flicker improves TBI prognosis, the effects and mechanism of rhythmic flicker on TBI remain unclear. In this study, we aimed to explore whether light flicker could reverse cognitive deficits, and further explore its potential mechanisms in TBI mouse model. The Morris water maze test (MWM), step-down test (SDT), and novel object recognition test (NOR) were applied to evaluate the cognitive ability. The local field potential (LFP) recording was applied to measure low gamma reduction of CA1 in hippocampus after TBI. And electrophysiological experiments were applied to explore effects of the gamma frequency entrainment on long-term potentiation (LTP), postsynaptic transmission, and intrinsic excitability of CA1 pyramidal cells (PCs) in TBI mice. Immunofluorescence staining and western blotting were applied to explore the effects of 40 Hz light flicker on the expression of PSD95 in hippocampus of TBI mice. We found that 40 Hz light flicker restored low gamma reduction of CA1 in hippocampus after TBI. And 40 Hz, but not random or 80 Hz light flicker, reversed cognitive impairment after TBI in behavioral tests. Moreover, 40 Hz light flicker improved N-methyl-D-aspartate (NMDA) receptor-dependent LTP (LTPNMDAR ) and L-type voltage-gated calcium channel-dependent LTP (LTPL-VGCC ) after TBI treatment. And gamma frequency entrainment decreased excitatory postsynaptic currents (EPSCs) of CA1 PCs in TBI mice. Our results have illustrated that 40 Hz light flicker could decrease intrinsic excitability of PCs after TBI treatment in mice. Furthermore, 40 Hz light flicker decreased the expression of PSD95 in hippocampus of TBI mice. These results demonstrated that 40 Hz light flicker rescues cognitive impairment by decreasing postsynaptic transmission in PCs after TBI treatment in mice.

Resveratrol reduces p38 mitogen-activated protein kinase phosphorylation by activating Sirtuin 1 to alleviate cognitive dysfunction after traumatic brain injury in mice.

Traumatic brain injury (TBI) is characterized by neuronal loss and subsequent brain damage and can be accompanied by transient or permanent neurological dysfunction. The recovery of cognitive function after TBI is a challenge. This study aimed at investigating whether treatment with resveratrol (RSV) could prevent cognitive dysfunction after TBI in mice. TBI mouse model using weight drop-impact method. Male mice aged from 7 to 9 weeks were randomly divided into four groups: TBI group, TBI + vehicle group, TBI + RSV group, and sham-operated control group. The animals from the TBI + vehicle group and TBI + RSV group were intraperitoneally injected at 3 and 24 h post-TBI with placebo and RSV (3%, 5 ml/kg), respectively. Two days after TBI, the hippocampus of mice was extracted, and western blot analysis was performed for Sirtuin 1 (SIRT1), synaptophysin (SYP), p38 mitogen-activated protein kinase (MAPK), and P-p38 MAPK. Moreover, behavioral functions of TBI mice were evaluated by Y maze to determine RSV efficacy in preventing cognitive impairment in TBI. RSV increased the expression of SIRT1 protein, which in turn activated the phosphorylation of p38 MAPK. Taken together, our findings suggest that RSV exerts a strong beneficial effect on improving neurological function induced by TBI.

Temporal order memory impairments in individuals with moderate-severe traumatic brain injury

ABSTRACT Introduction Temporal order memory is a core cognitive function that underlies much of our behavior. The ability to bind together information within and across events, and to reconstruct that sequence of information, critically relies upon the hippocampal relational memory system. Recent work has suggested traumatic brain injury (TBI) may particularly impact hippocampally mediated relational memory. However, it is currently unclear whether such deficits extend to temporal order memory, and whether deficits only arise at large memory loads. The present study assessed temporal order memory in individuals with chronic, moderate-severe TBI across multiple set sizes. Method Individuals with TBI and Neurotypical Comparison participants studied sequences of three to nine objects, one a time. At test, all items were re-presented in pseudorandom order, and participants indicated the temporal position (i.e., first, second, etc.) in which each object had appeared. Critically, we assessed both the frequency and the magnitude of errors (i.e., how far from its studied position was an item remembered). Results Individuals with TBI were not impaired for the smallest set size, but showed significant impairments at 5+ items. Group differences in the error frequency did not increase further with larger set sizes, but group differences in error magnitude did increase with larger memory loads. Individuals with TBI showed spared performance for the first object of each list (primacy) but were impaired on the last object (recency), though error frequency was better for last compared to middle items. Conclusions Our findings demonstrate that TBI results in impaired temporal order memory for lists as small as five items, and that impairments are exacerbated with increasing memory loads. Assessments that test only small set sizes may be insufficient to detect these deficits. Further, these data highlight the importance of additional, sensitive measures in the assessment of cognitive impairments in TBI.

Gait Impairment in Traumatic Brain Injury: A Systematic Review.

Introduction: Gait impairment occurs across the spectrum of traumatic brain injury (TBI); from mild (mTBI) to moderate (modTBI), to severe (sevTBI). Recent evidence suggests that objective gait assessment may be a surrogate marker for neurological impairment such as TBI. However, the most optimal method of objective gait assessment is still not well understood due to previous reliance on subjective assessment approaches. The purpose of this review was to examine objective assessment of gait impairments across the spectrum of TBI. Methods: PubMed, AMED, OVID and CINAHL databases were searched with a search strategy containing key search terms for TBI and gait. Original research articles reporting gait outcomes in adults with TBI (mTBI, modTBI, sevTBI) were included. Results: 156 citations were identified from the search, of these, 13 studies met the initial criteria and were included into the review. The findings from the reviewed studies suggest that gait is impaired in mTBI, modTBI and sevTBI (in acute and chronic stages), but methodological limitations were evident within all studies. Inertial measurement units were most used to assess gait, with single-task, dual-task and obstacle crossing conditions used. No studies examined gait across the full spectrum of TBI and all studies differed in their gait assessment protocols. Recommendations for future studies are provided. Conclusion: Gait was found to be impaired in TBI within the reviewed studies regardless of severity level (mTBI, modTBI, sevTBI), but methodological limitations of studies (transparency and reproducibility) limit clinical application. Further research is required to establish a standardised gait assessment procedure to fully determine gait impairment across the spectrum of TBI with comprehensive outcomes and consistent protocols.

Gait impairment in traumatic brain injury: A systematic review

Gait impairment in traumatic brain injury: A systematic review

Hyperbaric oxygen therapy

The extent and progression of neurological impairment in traumatic brain injury depend significantly on the area of perilesional gloom, where neuronal apoptosis occurs. Inhibition of apoptosis becomes a therapeutic strategy to preserve brain tissue and promote functional recovery. Hyperbaric oxygen therapy is a treatment by which 100% oxygen is administered, with the aim of achieving a higher pressure than atmospheric pressure at sea level, to decrease ischemia and intensity of inflammatory processes triggered, compromising the viability of the tissues. For mild traumatic brain injury, studies indicate that hyperbaric oxygen therapy is no better than sham treatment. For acute treatment of moderate to severe traumatic brain injury, although the methodology is questionable in certain studies due to the complexity of the brain injury, hyperbaric oxygen therapy has been shown to be beneficial as a relatively safe adjunctive therapy. The objective of this review is to discuss aspects related to the pathophysiology of traumatic brain injury, the mechanism of action of hyperbaric oxygen therapy, and correlate these results with the use of this therapy in the prevention of neuronal injury, supported by original studies reported in the scientific literature

Topological Aberrance of Structural Brain Network Provides Quantitative Substrates of Post-Traumatic Brain Injury Attention Deficits in Children.

Background: Traumatic brain injury (TBI)-induced attention deficits are among the most common long-term cognitive consequences in children. Most of the existing studies attempting to understand the neuropathological underpinnings of cognitive and behavioral impairments in TBI have utilized heterogeneous samples and resulted in inconsistent findings. The current research proposed to investigate topological properties of the structural brain network in children with TBI and their relationship with post-TBI attention problems in a more homogeneous subgroup of children who had severe post-TBI attention deficits (TBI-A). Materials and Methods: A total of 31 children with TBI-A and 35 group-matched controls were involved in the study. Diffusion tensor imaging-based probabilistic tractography and graph theoretical techniques were used to construct the structural brain network in each subject. Network topological properties were calculated in both global level and regional (nodal) level. Between-group comparisons among the topological network measures and analyses for searching brain-behavioral were all corrected for multiple comparisons using Bonferroni method. Results: Compared with controls, the TBI-A group showed significantly higher nodal local efficiency and nodal clustering coefficient in left inferior frontal gyrus and right transverse temporal gyrus, whereas significantly lower nodal clustering coefficient in left supramarginal gyrus and lower nodal local efficiency in left parahippocampal gyrus. The temporal lobe topological alterations were significantly associated with the post-TBI inattentive and hyperactive symptoms in the TBI-A group. Conclusion: The results suggest that TBI-related structural re-modularity in the white matter subnetworks associated with temporal lobe may play a critical role in the onset of severe post-TBI attention deficits in children. These findings provide valuable input for understanding the neurobiological substrates of post-TBI attention deficits, and have the potential to serve as quantitatively measurable criteria guiding the development of more timely and tailored strategies for diagnoses and treatments to the affected individuals. Impact statement This study provides a new insight into the neurobiological substrates associated with post-traumatic brain injury attention deficits (TBI-A) in children, by evaluating topological alterations of the structural brain network. The results demonstrated that relative to group-matched controls, the children with TBI-A had significantly altered nodal local efficiency and nodal clustering coefficient in temporal lobe, which strongly linked to elevated inattentive and hyperactive symptoms in the TBI-A group. These findings suggested that white matter structural re-modularity in subnetworks associated with temporal lobe may serve as quantitatively measurable biomarkers for early prediction and diagnosis of post-TBI attention deficits in children.

Efficacy of Non-invasive Brain Stimulation Methods for the Treatment of Cognitive Impairment in Traumatic Brain Injury and Stroke

Efficacy of Non-invasive Brain Stimulation Methods for the Treatment of Cognitive Impairment in Traumatic Brain Injury and Stroke

Omega-3 Polyunsaturated Fatty Acids Alleviate Traumatic Brain Injury by Regulating the Glymphatic Pathway in Mice.

Background: The glymphatic pathway has been shown to be impaired in traumatic brain injury (TBI). Omega-3 polysaturated fatty acids (Omega-3, PUFAs) are involved in the clearance of amyloid-ß through the glymphatic system and this effect is Aquaporin-4 (AQP4) dependent. We hypothesize that Omega-3 PUFAs can alleviate neurological impairment in TBI by protecting the glymphatic pathway.Methods: We pretreated mice with Omega-3 PUFAs rich fish oil and introduced TBI in the mice. Neurological functions were assessed through the modified neurological severity score (mNSS) system and Rota-rod test. Aß42 levels and radioisotope clearance were examined to determine the function of glymphatic system. AQP4 protein and mRNA expressions and its polarity were examined in fish oil treated TBI mice or control mice. Finally, the integrity of blood-brain barrier was determined by Evans blue extravasation and measurement of tight junction proteins (ZO-1 and Occludin) levels.Results: TBI surgery induced significant neurological functional impairment, Omega-3 PUFAs attenuated TBI-induced neurological impairment, as evidenced by reduced mNSS, improved performance in the Rota-rod test. Furthermore, Omega-3 PUFAs improved glymphatic clearance after induction of TBI in mice, reduced Aß42 accumulation, partially restored the clearance of both 3H-mannitol and 14C-Inulin. Omega-3 PUFAs also suppressed AQP4 expression and partially prevented loss of AQP4 polarity in mice undergoing TBI. Finally, Omega-3 PUFAs protected mice from TBI induced blood-brain barrier disruption.Conclusion: Omaga-3 PUFAs attenuate neurological function by partially restoring the AQP4 dependent glymphatic system in mice with TBI.

New Insights into Oxidative Damage and Iron Associated Impairment in Traumatic Brain Injury.

Traumatic Brain Injury is considered one of the most prevalent causes of death around the world; more than seventy millions of individuals sustain the condition per year. The consequences of traumatic brain injury on brain tissue are complex and multifactorial, hence, the current palliative treatments are limited to improve patients' quality of life. The subsequent hemorrhage caused by trauma and the ongoing oxidative process generated by biochemical disturbances in the in the brain tissue may increase iron levels and reactive oxygen species. The relationship between oxidative damage and the traumatic brain injury is well known, for that reason, diminishing factors that potentiate the production of reactive oxygen species have a promissory therapeutic use. Iron chelators are molecules capable of scavenging the oxidative damage from the brain tissue and are currently in use for ironoverload- derived diseases. Here, we show an updated overview of the underlying mechanisms of the oxidative damage after traumatic brain injury. Later, we introduced the potential use of iron chelators as neuroprotective compounds for traumatic brain injury, highlighting the action mechanisms of iron chelators and their current clinical applications.

Autoregulation assessment by direct visualisation of pial arterial blood flow in the piglet brain

Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.

A Pilot Investigation of Repetitive Transcranial Magnetic Stimulation for Post-Traumatic Brain Injury Depression: Safety, Tolerability, and Efficacy.

Depression following a traumatic brain injury (TBI) is common and difficult to treat using standard approaches. The current study investigated, for the first time, transcranial magnetic stimulation (TMS) for the treatment of post TBI depression. We specifically assessed the safety, tolerability, and efficacy of TMS in this patient population. We also explored cognitive outcomes. Twenty-one patients with a current episode of major depression subsequent to a TBI participated in a randomized double-blind placebo-controlled trial of repetitive TMS (rTMS). Sequential bilateral rTMS (to the left and right dorsolateral prefrontal cortex) was provided in 20 treatments over a period of 4 weeks. Patients were randomly allocated to receive either active or sham stimulation. There were no adverse effects and treatment was well tolerated. There was no significant effect of rTMS on post-TBI depression, with all patients showing a significant improvement in depressive symptoms irrespective of their treatment group (p = 0.002). There were significant improvements in cognition following active rTMS in the areas of working memory (p = 0.021) and executive function (p = 0.029). rTMS was shown to be safe and well tolerated in patients who had developed depression after a TBI. We did not find a therapeutic effect for post-TBI depression; however, this approach may have some utility in improving cognitive function. Future research should focus on alternative rTMS treatment approaches for post-TBI depression and the direct investigation of rTMS as a treatment for cognitive impairment in TBI.

Facial-affect recognition deficit as a predictor of different aspects of social-communication impairment in traumatic brain injury.

To examine the relationship between facial-affect recognition and different aspects of self- and proxy-reported social-communication impairment following moderate-severe traumatic brain injury (TBI). Forty-six adults with chronic TBI (>6 months postinjury) and 42 healthy comparison (HC) adults were administered the La Trobe Communication Questionnaire (LCQ) Self and Other forms to assess different aspects of communication competence and the Emotion Recognition Test (ERT) to measure their ability to recognize facial affects. Individuals with TBI underperformed HC adults in the ERT and self-reported, as well as were reported by close others, as having more communication problems than did HC adults. TBI group ERT scores were significantly and negatively correlated with LCQ-Other (but not LCQ-Self) scores (i.e., participants with lower emotion-recognition scores were rated by close others as having more communication problems). Multivariate regression analysis revealed that adults with higher ERT scores self-reported more problems with disinhibition-impulsivity and partner sensitivity and had fewer other-reported problems with disinhibition-impulsivity and conversational effectiveness. Our findings support growing evidence that emotion-recognition deficits play a role in specific aspects of social-communication outcomes after TBI and should be considered in treatment planning. (PsycINFO Database Record

Supplemental Material for Facial-Affect Recognition Deficit as a Predictor of Different Aspects of Social-Communication Impairment in Traumatic Brain Injury

Supplemental Material for Facial-Affect Recognition Deficit as a Predictor of Different Aspects of Social-Communication Impairment in Traumatic Brain Injury

A Brain Electrical Activity Electroencephalographic-Based Biomarker of Functional Impairment in Traumatic Brain Injury: A Multi-Site Validation Trial

The potential clinical utility of a novel quantitative electroencephalographic (EEG)-based Brain Function Index (BFI) as a measure of the presence and severity of functional brain injury was studied as part of an independent prospective validation trial. The BFI was derived using quantitative EEG (QEEG) features associated with functional brain impairment reflecting current consensus on the physiology of concussive injury. Seven hundred and twenty adult patients (18-85 years of age) evaluated within 72 h of sustaining a closed head injury were enrolled at 11 U.S. emergency departments (EDs). Glasgow Coma Scale (GCS) score was 15 in 97%. Standard clinical evaluations were conducted and 5 to 10 min of EEG acquired from frontal locations. Clinical utility of the BFI was assessed for raw scores and percentile values. A multinomial logistic regression analysis demonstrated that the odds ratios (computed against controls) of the mild and moderate functionally impaired groups were significantly different from the odds ratio of the computed tomography (CT) postive (CT+, structural injury visible on CT) group (p = 0.0009 and p = 0.0026, respectively). However, no significant differences were observed between the odds ratios of the mild and moderately functionally impaired groups. Analysis of variance (ANOVA) demonstrated significant differences in BFI among normal (16.8%), mild TBI (mTBI)/concussed with mild or moderate functional impairment, (61.3%), and CT+ (21.9%) patients (p < 0.0001). Regression slopes of the odds ratios for likelihood of group membership suggest a relationship between the BFI and severity of impairment. Findings support the BFI as a quantitative marker of brain function impairment, which scaled with severity of functional impairment in mTBI patients. When integrated into the clinical assessment, the BFI has the potential to aid in early diagnosis and thereby potential to impact the sequelae of TBI by providing an objective marker that is available at the point of care, hand-held, non-invasive, and rapid to obtain.

Relationship between individual differences in functional connectivity and facial-emotion recognition abilities in adults with traumatic brain injury.

Although several studies have demonstrated that facial-affect recognition impairment is common following moderate-severe traumatic brain injury (TBI), and that there are diffuse alterations in large-scale functional brain networks in TBI populations, little is known about the relationship between the two. Here, in a sample of 26 participants with TBI and 20 healthy comparison participants (HC) we measured facial-affect recognition abilities and resting-state functional connectivity (rs-FC) using fMRI. We then used network-based statistics to examine (A) the presence of rs-FC differences between individuals with TBI and HC within the facial-affect processing network, and (B) the association between inter-individual differences in emotion recognition skills and rs-FC within the facial-affect processing network. We found that participants with TBI showed significantly lower rs-FC in a component comprising homotopic and within-hemisphere, anterior-posterior connections within the facial-affect processing network. In addition, within the TBI group, participants with higher emotion-labeling skills showed stronger rs-FC within a network comprised of intra- and inter-hemispheric bilateral connections. Findings indicate that the ability to successfully recognize facial-affect after TBI is related to rs-FC within components of facial-affective networks, and provide new evidence that further our understanding of the mechanisms underlying emotion recognition impairment in TBI.