History Of mTBI Research Articles

Self-reported dizziness, balance, and multisensory impairment following mild traumatic brain injury: an exploratory study

ABSTRACT Dizziness following mild traumatic brain injury (mTBI), or concussion, is common and can encompass multiple sensations reflecting diverse aetiologies. This exploratory study investigated the types of dizzy sensations experienced, their evolution, and relationship with other post-concussion symptoms. Thirty New Zealanders (24 female) aged 49 ± 16 years who experienced dizziness or imbalance following their injury completed the Dizziness Handicap Inventory, Visual Vertigo Analogue Scale, and the Hospital Anxiety and Depression Scale. Additional custom questionnaires probed subjective experiences of dizziness and balance, headaches, and difficulties with auditory processing and vision. Just over half the participants (56.7%) experienced a single mTBI. The median time interval since the injury was 16 months (IQR = 24 months). Participants usually reported multiple dizzy symptoms which developed within a week of the injury, although delays of up to six months were reported. Most participants (70%) felt their symptoms improved over time, while lack of improvement was associated with a history of multiple mTBI (P = 0.020). Moderate to strong correlations between questionnaire scores representing dizziness handicap, visual vertigo severity, and auditory processing difficulties (P < 0.001) suggest that dizziness and sensory impairment following mTBI are multi-modal and likely to benefit from holistic, multidisciplinary treatment.

Neurocognitive Intraindividual Variability in Veterans with Mild Traumatic Brain Injury History and Posttraumatic Stress Disorder.

Veterans with a history of blast-related mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may be at risk for greater cognitive concerns and worse functional outcomes compared to those with either condition in isolation. However, traditional neuropsychological assessment approaches have yielded equivocal results in these populations. The present study examined an alternative method for detecting subtle cognitive inefficiencies: neurocognitive intraindividual variability (IIV), a measure of within-person performance consistency. Participants were 79 male Veterans with a history of blast-related mTBI and current PTSD (mTBI/PTSD group; n = 54) or neither diagnosis (controls; n = 25). Mean T-scores and IIV scores were calculated from neuropsychological measures of attention and speed of information processing (A/SoP) as well as executive functioning (EF). Global IIV was significantly higher in the mTBI/PTSD group compared to controls (p = .047, Cohen's d = 0.49). At the domain level, larger effect sizes were observed for EF IIV (Cohen's d = 0.46) compared to A/SoP IIV (d = 0.32), although neither were statistically significant. Within the mTBI/PTSD group, higher Global IIV was associated with worse self-reported executive dysfunction, psychological quality of life, and cognitive post-concussive symptoms; at the domain level, these clinical outcomes were generally associated with greater A/SoP IIV (but not EF IIV). Findings extend previous investigations of neurocognitive IIV in individuals with a history of mTBI across PTSD status. Among Veterans with a history of mTBI and comorbid PTSD, neurocognitive variability may be a better indicator of self-reported cognitive inefficiencies and Veteran experience of daily cognitive functioning than mean neuropsychological performances.

Traumatic brain injury rehabilitation for warfighters with post-traumatic stress.

While there is extensive empirical support and clinical guidance for the treatment of mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) individually, less is known about treating the comorbid presentation of both conditions. The purpose of this review article is to provide information on the mental health treatment needs of service members (SMs) engaged in traumatic brain injury (TBI) rehabilitation. It also aims to offer a framework for an integrated treatment approach to address the cognitive and psychological health needs of warfighters. We review the prevalence and outcomes associated with comorbid TBI and PTSD and present relevant access to care considerations. Additionally, we identify an integrated approach to TBI treatment which takes psychological trauma into consideration. We introduce a trauma-informed care (TIC) model with specified diagnostic and treatment considerations for the service member and veteran (SM/V) communities. TIC is a strengths-based framework that raises the system-wide awareness of treatment facilities to the impact of psychological trauma on behavioral health. A comprehensive diagnostic approach is recommended with considerations for symptom etiology. Clinical considerations derived from available guidelines are identified to meet critical treatment needs for SM/Vs presenting for TBI treatment with a remote history of mTBI and psychological trauma or known PTSD. Clinical practice guidelines are used to inform an integrated TBI treatment model and maximize rehabilitation efforts for warfighters. Given the prevalence of comorbid TBI and PTSD among SM/Vs and its impact on outcomes, this review presents the integration of appropriate diagnostics and treatment practices, including the incorporation of CPGs into TBI rehabilitation.

The Role of Hearing Difficulty: Cognitive-Communication and Speech-in-Noise Deficits in Adults Following Mild Traumatic Brain Injury

Purpose: Mild traumatic brain injury (TBI) has a high rate of occurrence across the lifespan. Following mild TBI (mTBI), perceived deficits in cognitive communication and hearing may be noted. This study aimed to determine if adults with a history of mTBI and hearing difficulty perceived greater degrees of cognitive-communication difficulty and performed poorer on a speech-in-noise task when compared to participants with mTBI and controls without reported hearing difficulty. Method: Adults aged 19–77 years with and without a history of mTBI were analyzed. Participants were divided into three groups: control ( n = 49), mTBI ( n = 22), and mTBI with hearing difficulty (mTBI-HD, n = 26). Perception of hearing difficulty was based on a score of ≥ 20 on the Hearing Handicap Inventory or a score ≥ 2 on the Adult Auditory Performance Scale. Self-perceived cognitive communication was measured using the Cognitive Difficulties Scale (CDS) and the La Trobe Communication Questionnaire (LCQ). Speech-in-noise performance was measured using the low-cue speech recognition threshold (SRT) from the Listening in Spatialized Noise–Sentences (LiSN-S) test. Results: Adults in the mTBI-HD group reported significantly greater degrees of cognitive-communication difficulties (higher CDS and LCQ scores) and exhibited significantly poorer speech-in-noise performance on the low-cue LiSN-S condition when compared to the control and mTBI groups. Results also revealed significant correlations between the LiSN-S low-cue SRT and perceived cognitive communication on the CDS. Conclusions: Results of the current study indicate that adults with a history of mTBI and hearing difficulty experience greater subjective cognitive-communication difficulties and perform more poorly on difficult speech-in-noise tasks than adults who do not experience self-perceived hearing difficulties. The results of this study support the consideration of hearing and cognitive-communication difficulties when determining appropriate speech, language, and hearing assessment, treatment, and intervention strategies for individuals following mTBI.

Examination of Congruity between Subjective and Objective Working Memory in Veterans with Mild TBI and Relation to Psychiatric Symptoms and Childhood Trauma.

There is conflicting evidence regarding congruence between subjective cognitive decline and objective cognitive performance for individuals with a history of mild traumatic brain injury (mTBI). The current study investigated the congruity between subjective and objective cognition, particularly working memory, among veterans with an mTBI history, accounting for post-traumatic stress disorder (PTSD) and childhood trauma. Participants included 35 veterans with a history of mTBI sustained during deployment. Participants completed measures of subjective [i.e., Behavioral Inventory Rating of Executive Functioning (BRIEF)] and objective working memory (i.e., WAIS-IV working memory index). Congruity between subjective and objective working memory was examined using linear regression. Bonferroni-corrected correlations were run to explore relationships among working memory, psychiatric symptoms, mTBI severity, and childhood trauma. Among Veterans with mTBI, subjective working memory and objective working memory performance were not significantly related (p > 0.05); however, the overall model was significant (p < 0.0001), and childhood trauma was a notable predictor (p = 0.02). Greater PTSD, depression, and sleep symptoms were significantly related to increased subjective working memory concerns, even after Bonferroni adjustments (ps < 0.0001). Better objective working memory was significantly related to a fewer number of childhood traumatic events; however, this did not sustain corrections. The majority of individuals (67%) endorsed significant working memory complaints, despite objectively performing within normal limits (within 1 SD and above). Subjective-objective working memory congruity among veterans with mTBI was limited. Subjective, but not objective, working memory concerns were associated with greater PTSD, depression, and sleep symptoms. Childhood trauma was a notable factor that contributed to both subjective and objective cognitive concerns. There remains clinical value in assessing subjective cognitive concerns given the strong relationships with psychiatric problems and, hence, a focus for intervention.

7280 Pituitary Dysfunction Following Mild Traumatic Brain Injury in Female Athletes: Neuropsychological and Psychological Functioning

Abstract Disclosure: L.Ó. Eggertsdóttir Claessen: None. M.K. Jónsdóttir: None. H. Kristjánsdóttir: None. S.H. Lund: None. I. Unnsteinsdóttir Kristensen: None. H.Á. Sigurjónsdóttir: None. Background: Pituitary dysfunction (PD), as well as neuropsychological and psychological symptoms, have been reported following mild traumatic brain injury (mTBI). These symptoms may be due to the brain injury itself or PD as hypopituitarism (HP) can have neuropsychological and psychological effects. To the best of our knowledge, this study is the first to report neuropsychological and psychological outcomes in female athletes with PD following sport-related mTBI. Subjects: Female athletes aged 18 to 45 years currently active in or retired from soccer, team handball, basketball, ice hockey, and martial arts who answered an online questionnaire regarding mTBI history and mental health were included (n = 508). Of the 308 women who reported one or more mTBI, 166 (53.8%) accepted to participate in a further interview and neuropsychological tests. All 166 women were subsequently invited to participate in a medical interview. Of those 151 accepted (90.9%) and 131 (86.7%) of them participated in pituitary hormone screening blood tests (SBT). Methods: The online questionnaire included a post-concussion symptom scale, and mental health scales evaluating symptoms of anxiety, depression, stress, and quality of life. Sleep disturbances were evaluated, and neuropsychological tests were performed in the psychological interview. The Sustained Attention to Response Task (SART). Executive functioning, visual search, motor and processing speed, divided attention, working memory, and intellectual abilities were also measured. The SBT were taken at 8 a.m. and included S-IGF1 (age dependant reference range), S-cortisol (values &amp;lt; 350 nmol/L were considered abnormal), S-prolactin (reference range 4.79 - 23.3 μg/L), S-TSH (reference range 0.270 - 4.20 mIU/L), S-fT4 (reference range 12 - 22 pmol/L), S-FSH, S-oestrogen, and S-progesterone measurements. If SBT were repeatedly O-RV, detailed endocrinological tests were performed for each axis as indicated. Results: Following a detailed endocrinological evaluation, 16 women were diagnosed with PD (HP n = 6, hyperprolactinemia n = 10) following mTBI. Women with PD had a significantly higher mean SART error score than women with normal pituitary function (PF) (16.7 and 12.8 respectively; p = 0.04). No other significant differences in neuropsychological outcome were found between the two groups. Moreover, there was not a significant difference with regards to mTBI symptoms, anxiety, depression, stress, QOL or insomnia between women with PD and those with normal PF. Conclusions: Sustained attention or inhibitory performance may be affected in women with PD following mTBI as they had a higher mean SART error score than women with normal PF. No other significant difference in neuropsychological or psychological outcome was demonstrated. Presentation: 6/3/2024

Aerobic Exercise, Mtbi History, And Health-related Quality Of Life Among Military Service Members And Veterans.

Aerobic Exercise, Mtbi History, And Health-related Quality Of Life Among Military Service Members And Veterans.

On the lasting impact of mild traumatic brain injury on working memory: Behavioural and electrophysiological evidence

Despite increasing recognition of the significance of mild traumatic brain injury (mTBI), the long-term cognitive consequences of the injury remain unclear. More sensitive measures that can detect subtle cognitive changes and consideration of individual variability are needed to properly characterise cognitive outcomes following mTBI. Here, we used complex behavioural tasks, individual differences approaches, and electrophysiology to investigate the long-term cognitive effects of a history of mTBI. In Experiment 1, participants with self-reported mTBI history (n=82) showed poorer verbal working memory performance on the operation span task compared to control participants (n=88), but there were no group differences in visual working memory, multitasking, cognitive flexibility, attentional control, visuospatial ability, or information processing speed. Individual differences analyses revealed that time since injury and presence of memory loss predicted visual working memory capacity and visuospatial ability, respectively, in those with mTBI history. In Experiment 2, participants with mTBI history (n=20) again demonstrated poorer verbal working memory on the operation span task compared to control participants (n=38), but no group differences were revealed on a visuospatial complex span task or simpler visual working memory measures. We also explored the electrophysiological indices of visual working memory using EEG during a change detection task. No differences were observed in early sensory event-related potentials (P1, N1) or the later negative slow wave associated with visual working memory capacity. Together, these findings suggest that mTBI history may be associated with a lasting, isolated disruption in the subsystem underlying verbal working memory storage. The results emphasise the importance of sensitive cognitive measures and accounting for individual variability in injury characteristics when assessing mTBI outcomes.

B - 39 Resilience in Active Duty US Military Service Members: Factor Analysis and Prediction of Psychological Symptoms in a Mild Traumatic Brain Injury Sample

Abstract Objective The factor structure of the Connor-Davidson Resilience Scale (CD-RISC) varies between cultures, settings, and samples, yet has not been assessed in an active-duty United States (US) military sample. We used factor analysis to characterize resilience in a generalizable sample of active-duty service members (ADSMs) and explored its associations with self-reported psychological outcomes in ADSMs with a history of mild traumatic brain injury (mTBI). Method Exploratory factor analysis (EFA) of the 25-item CD-RISC was performed on a non-clinical convenience sample of 212 active duty SMs followed by a confirmatory factor analysis (CFA) for model validation. Hierarchical regressions compared the relationships among the resulting factors and total scores on the Post Traumatic Stress Disorder Checklist (PCL-5), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) between subgroups with self-reported history of mTBI (n = 60) and TBI-negative controls (n = 54). Results EFA returned a 4-factor, 19-item solution. After modifications to improve model fit, CFA validated a 4-factor, 17-item solution: Fortitude, Resoluteness, Decisiveness, and Dedication. The interaction of TBI history with the Decisiveness and Dedication factors significantly predicted BDI and PCL-5 total scores (p &amp;lt; 0.05), but not BAI total scores. Fortitude and Resoluteness did not differentially predict any psychological outcomes between groups. Conclusion Four latent factors of resilience that are unique to ADSMs were identified and validated from the 25-item CD-RISC. Decisiveness and Dedication more strongly predicted depressive and PTSD symptoms in ADSMs with a history of mTBI than in controls, suggesting these factors of resilience are especially critical for better psychological outcomes following mTBI in military populations.

White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

The Impact of Non-Pain Factors on Pain Interference Among U.S. Service Members and Veterans with Symptoms of Mild Traumatic Brain Injury.

U.S. Service members and Veterans (SM/V) experience elevated rates of traumatic brain injury (TBI), chronic pain, and other non-pain symptoms. However, the role of non-pain factors on pain interference levels remains unclear among SM/Vs, particularly those with a history of TBI. The primary objective of this study was to identify factors that differentiate high/low pain interference, given equivalent pain intensity among U.S. SM/V participating in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) national multi-center prospective longitudinal observational study. An explainable machine learning was used to identify key predictors of pain interference conditioned on equivalent pain intensity. The final sample consisted of n = 1,577 SM/Vs who were predominantly male (87%), and 83.6% had a history of mild TBI(s) (mTBI), while 16.4% were TBI negative controls. The sample was categorized according to pain interference level (Low: 19.9%, Moderate: 52.5%, and High: 27.6%). Both pain intensity scores and pain interference scores increased with the number of mTBIs (p < 0.001), and there was evidence of a dose response between the number of injuries and pain scores. Machine learning models identified fatigue and anxiety as the most important predictors of pain interference, whereas emotional control was protective. Partial dependence plots identified that marginal effects of fatigue and anxiety were associated with pain interference (p < 0.001), but the marginal effect of mTBI was not significant in models considering all variables (p > 0.05). Non-pain factors are associated with functional limitations and disability experience among SM/V with an mTBI history. The functional effects of pain may be mediated through multiple other factors. Pain is a multi-dimensional experience that may benefit most from holistic treatment approaches that target comorbidities and build supports that promote recovery.

Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI2 sponsored protocol.

Sleep-wake disturbances frequently present in Veterans with mild traumatic brain injury (mTBI). These TBI-related sleep impairments confer significant burden and commonly exacerbate other functional impairments. Therapies to improve sleep following mTBI are limited and studies in Veterans are even more scarce. In our previous pilot work, morning bright light therapy (MBLT) was found to be a feasible behavioral sleep intervention in Veterans with a history of mTBI; however, this was single-arm, open-label, and non-randomized, and therefore was not intended to establish efficacy. The present study, LION (light vs ion therapy) extends this preliminary work as a fully powered, sham-controlled, participant-masked randomized controlled trial (NCT03968874), implemented as fully remote within the VA (target n=120 complete). Randomization at 2:1 allocation ratio to: 1) active: MBLT (n=80), and 2) sham: deactivated negative ion generator (n=40); each with identical engagement parameters (60-min duration; within 2-hrs of waking; daily over 28-day duration). Participant masking via deception balanced expectancy assumptions across arms. Outcome measures were assessed following a 14-day baseline (pre-intervention), following 28-days of device engagement (post-intervention), and 28-days after the post-intervention assessment (follow-up). Primary outcomes were sleep measures, including continuous wrist-based actigraphy, self-report, and daily sleep dairy entries. Secondary/exploratory outcomes included cognition, mood, quality of life, circadian rhythm via dim light melatonin onset, and biofluid-based biomarkers. Participant drop out occurred in <10% of those enrolled, incomplete/missing data was present in <15% of key outcome variables, and overall fidelity adherence to the intervention was >85%, collectively establishing feasibility and acceptability for MBLT in Veterans with mTBI.

Prospective memory performance in veterans with and without histories of mild traumatic brain injury: effect of the apolipoprotein E (APOE) ε4 genotype

ABSTRACT Objective Identifying factors that moderate cognitive outcomes following mild traumatic brain injury (mTBI) is crucial. Prospective memory (PM) is a cognitive domain of interest in mTBI recovery as it may be especially sensitive to TBI-related changes. Since studies show that genetic status – particularly possession of the apolipoprotein E (APOE) ε4 allele – can modify PM performance, we investigated associations between mTBI status and APOE-ε4 genotype on PM performance in a well-characterized sample of Veterans with neurotrauma histories. Methods 59 Veterans (mTBI = 33, Military Controls [MCs] = 26; age range: 24–50; average years post-injury = 10.41) underwent a structured clinical interview, neuropsychological assessment, and genotyping. The Memory for Intentions Test (MIST) measured PM across multiple subscales. ANCOVAs, adjusting for age and posttraumatic stress symptoms, tested the effects of mTBI status (mTBI vs. MC) and ε4 status (ε4+ vs. ε4−) on MIST scores. Results Veterans with mTBI history performed more poorly compared to MCs on the MIST 15-min delay (p=.002, ηp 2 =.160), Time Cue (p = .003, ηp 2 =.157), and PM Total (p = .016, ηp 2 =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay (p = .011, ηp 2 =.113) and PM Total (p = .048, ηp 2 = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (ps>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4− Veterans on the MIST 15-min delay subscale (p = .031, ηp 2 = .150). Conclusions mTBI history and APOE-ε4 genotype status were independently associated with worse PM performance compared to those without head injury histories or possession of the APOE-e4 genotype. Performance on the MIST 15-min delay was worse in Veterans with both risk factors (mTBI history and APOE-ε4 positivity). Findings suggest that genetic status may modify outcomes even in relatively young Veterans with mTBI histories. Future research examining longitudinal associations and links to neuroimaging and biomarker data are needed.

White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis. To examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). This case-control study examined 98 male service members enrolled in a study at the National Intrepid Center of Excellence. Eligible participants were active duty status or able to enroll in the Defense Enrollment Eligibility Reporting system, ages 18 to 60 years, and had a remote history of mTBI; controls were matched by age. Remote history of mTBI. White matter microstructure was assessed using a region-of-interest approach of skeletonized diffusion images, including DTI (fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity) and NODDI (orientation dispersion index [ODI], isotropic volume fraction, intra-cellular volume fraction). Neuropsychiatric outcomes associated with posttraumatic stress disorder (PTSD) and postconcussion syndrome were assessed. A total of 65 male patients with a remote history of mTBI (mean [SD] age, 40.5 [5.0] years) and 33 age-matched male controls (mean [SD] age, 38.9 [5.6] years) were included in analysis. Compared with the control cohort, the 65 service members with mTBI presented with significantly more severe PTSD-like symptoms (mean [SD] PTSD CheckList-Civilian [PCL-C] version scores: control, 19.0 [3.8] vs mTBI, 41.2 [11.6]; P < .001). DTI and NODDI metrics were altered in the mTBI group compared with the control, including intra-cellular volume fraction of the right cortico-spinal tract (β = -0.029, Cohen d = 0.66; P < .001), ODI of the left posterior thalamic radiation (β = -0.006, Cohen d = 0.55; P < .001), and ODI of the left uncinate fasciculus (β = 0.013, Cohen d = 0.61; P < .001). In service members with mTBI, fractional anisotropy of the left uncinate fasciculus was associated with postconcussion syndrome (β = 5.4 × 10-3; P = .003), isotropic volume fraction of the genu of the corpus callosum with PCL-C (β = 4.3 × 10-4; P = .01), and ODI of the left fornix and stria terminalis with PCL-C avoidance scores (β = 1.2 × 10-3; P = .02). In this case-control study of military-related mTBI, the results suggest that advanced magnetic resonance imaging techniques using NODDI can reveal white matter microstructural alterations associated with neuropsychiatric symptoms in the chronic phase of mTBI. Diffusion trends observed throughout widespread white matter regions-of-interest may reflect mechanisms of neurodegeneration as well as postinjury tissue scarring and reorganization.

Executive functioning, behavior, and white matter microstructure in the chronic phase after pediatric mild traumatic brain injury: results from the adolescent brain cognitive development study.

Mild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown. Children with a history of mTBI (n = 406; Mage = 10 years, SDage = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or 8-10 years to the respective matched TDC controls. Fractional anisotropy (FA) and mean diffusivity (MD), both MRI-based measures of white matter microstructure, were compared between children with mTBI and controls. Children with a history of mTBI displayed higher parent-rated executive dysfunction, higher impulsivity, and poorer self-regulation compared to both control groups. At closer investigation, these differences to TDC were only present in one respective age-at-injury group. No alterations were found in task-based executive functioning or white matter microstructure. Findings suggest that everyday executive function, impulsivity, and emotion-regulation are affected years after pediatric mTBI. Outcomes were specific to the age at which the injury occurred, suggesting that functioning is differently affected by pediatric mTBI during vulnerable periods. Groups did not differ in white matter microstructure.

Reduced influence of perceptual context in mild traumatic brain injury is not an illusion.

Perceptual grouping is impaired following mild traumatic brain injury (mTBI). This may affect visual size perception, a process influenced by perceptual grouping abilities. We conducted two experiments to evaluate visual size perception in people with self-reported history of mTBI, using two different size-contrast illusions: the Ebbinghaus Illusion (Experiment 1) and the Müller-Lyer illusion (Experiment 2). In Experiment 1, individuals with mTBI and healthy controls were asked to compare the size of two target circles that were either the same size or different sizes. The target circles appeared by themselves (no-context condition), or were surrounded by smaller or larger circles (context condition). Similar levels of accuracy were evident between the groups in the no-context condition. However, size judgements by mTBI participants were more accurate in the context condition, suggesting that they processed the target circles separately from the surrounding circles. In Experiment 2, individuals with mTBI and healthy controls judged the length of parallel lines that appeared with arrowheads (context condition) or without arrowheads (no context condition). Consistent with Experiment 1, size judgements by mTBI participants were more accurate than size judgements by control participants in the context condition. These findings suggest that mTBI influences size perception by impairing perceptual grouping of visual stimuli in near proximity.

The relationship between blast-related mild traumatic brain injury and executive function is moderated by white matter integrity.

Blast-related mild traumatic brain injury (BR mTBI) is a critical research area in recent combat veterans due to increased prevalence of survived blasts. Post-BR mTBI outcomes are highly heterogeneous and defining neurological differences may help in discrimination and prediction of cognitive outcomes. This study investigates whether white matter integrity, measured with diffusion tensor imaging (DTI), could influence how remote BR mTBI history is associated with executive control. The sample included 151 Veterans from the Minneapolis Veterans Affairs Medical Center who were administered a clinical/TBI assessment, neuropsychological battery, and DTI scan as part of a larger battery. From previous research, six white matter tracts were identified as having a putative relationship with blast severity: the cingulum, hippocampal cingulum, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and uncinate. Fractional anisotropy (FA) of the a priori selected white matter tracts and report of BR mTBI were used as predictors of Trail-Making Test B (TMT-B) performance in a multiple linear regression model. Statistical analysis revealed that FA of the hippocampal cingulum moderated the association between report of at least one BR mTBI and poorer TMT-B performance (p < 0.008), such that lower FA value was associated with worse TMT-B outcomes in individuals with BR mTBI. No significant moderation existed for other selected tracts, and the effect was not observed with predictors aside from history of BR mTBI. Investigation at the individual-tract level may lead to a deeper understanding of neurological differences between blast-related and non-blast related injuries.

Sex-specific antioxidant biomarker depletion in patients with a history of mild traumatic brain injury

Individuals with a history of mild traumatic brain injury (mTBI) are at an increased risk for neurodegenerative disease, suggesting that intrinsic neuroprotective mechanisms, such as the endogenous antioxidant reservoir, may be depleted long-term after mTBI. Here, we retrospectively analyzed symptoms and blood antioxidants in patients with a history of mTBI who presented to Resilience Code, a sports medicine clinic in Colorado. Significant decreases in alpha-tocopherol, selenium, linoleic acid, taurine, docosahexaenoic acid, and total omega-3 were measured in the total mTBI population versus controls. Male mTBI patients showed depletion of a larger array of antioxidants than females. Patients with a history of mTBI also reported significantly worsened emotional, energy, head, and cognitive symptoms, with males displaying more extensive symptomology. Multiple or chronic mTBI patients had worsened symptoms than single or acute/subchronic mTBI patients, respectively. Finally, male mTBI patients with the largest reductions in polyunsaturated fatty acids (PUFAs) displayed worse symptomology than male mTBI patients with less depletion of this antioxidant reservoir. These results demonstrate that antioxidant depletion persists in patients with a history of mTBI and these deficits are sex-specific and associated with worsened symptomology. Furthermore, supplementation with specific antioxidants, like PUFAs, may diminish symptom severity in patients suffering from chronic effects of mTBI.

Persistent MRI Findings Unique to Blast and Repetitive Mild TBI: Analysis of the CENC/LIMBIC Cohort Injury Characteristics.

MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements. Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor. After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non-blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus. In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.

Mild Traumatic Brain Injury andCareer Stage Associate with Visible Perivascular Spaces in Special Operations Forces Soldiers.

Mild traumatic brain injury (mTBI) and occupational blast exposure in military Service Members may lead to impaired brain waste clearance which increases neurological disease risk. Perivascular spaces (PVS) are a key part of the glymphatic system which supports brain waste clearance, preferentially during sleep. Visible PVS on clinical magnetic resonance imaging have been previously observed in patients with neurodegenerative diseases and animal neurotrauma models. The purpose of this study was to determine associations between PVS morphological characteristics, military career stage, and mTBI history in Special Operations Forces (SOF)Soldiers. Participants underwent T2-weighed neuroimaging to capture three-dimensional whole brain volumes. Segmentation was performed using a previously validated, multi-scale deep convolutional encoder-decoder neural network. Only PVS clusters within the white matter mask were quantified for analyses. Due to non-normal PVS metric distribution, non-parametric Mann-Whitney U tests were used to determine group differences in PVS outcomes. In total, 223 healthy SOF combat Soldiers (age = 33.1 ± 4.3yrs) were included, 217 reported career stage. Soldiers with mTBI history had greater PVS number (z = 2.51, P = 0.013) and PVS volume (z = 2.42, P = 0.016). In-career SOF combat Soldiers had greater PVS number (z = 2.56, P = 0.01) and PVS volume (z = 2.28, P = 0.02) compared to a baseline cohort. Mild TBI history is associated with increased PVS burden in SOF combat Soldiers that are clinically recovered from mTBI. This may indicate ongoing physiological changes that could lead to impaired waste clearance via the glymphatic system. Future studies should determine if PVS number and volume are meaningful neurobiological outcomes for neurodegenerative disease risk and if clinical interventions such as improving sleep can reduce PVS burden.