mTBI Population Research Articles

Rasch analysis of the depression anxiety stress scales-21 (DASS-21) in a mild traumatic brain injury sample.

In this study, we evaluated the psychometric properties of the Depression Anxiety Stress Scales 21 items (DASS-21) in a mild traumatic brain injury (mTBI) sample. Treatment-seeking adults (n = 347) were recruited from outpatient rehabilitation services in New Zealand. Dimensionality, reliability, person separation index, and differential item functioning (DIF) of the DASS-21 were examined using Rasch analysis. Initial analysis of the complete 21-item DASS showed poor overall fit due to problems with individual items. Fit to the Rasch model was excellent when treated as three composite scores. The stress subscale demonstrated adequate model fit, dimensionality and good reliability. For anxiety, fit was not good, reliability was unsatisfactory and DIF was evident on one item. When this item was removed, fit to the model was still inadequate as was reliability. DIF was also evident for depression, but when this item was removed, fit to the model was adequate. The DASS-21 is a psychometrically sound measure of distress and stress for adults seeking treatment following mTBI. Ordinal to interval score conversion tables are provided to increase the precision of measurement. When assessing depression in a mTBI population, a 6-item depression subscale is recommended. Caution is advised in using the DASS-21 anxiety subscale alone.

LIMBIC-CENC: Successfully conducting longitudinal mTBI research during the COVID-19 pandemic.

Conducting mild traumatic brain injury (mTBI) longitudinal studies across multiple sites is a challenging endeavor which has been made more challenging because of COVID-19. This article briefly describes several concerns that need to be addressed during the conduct of research to account for COVID-19's impact. The recent actions and steps taken by the Long-term Impact of Military-relevant Brain Injury Consortium (LIMBIC)-Chronic Effects of Neurotrauma Consortium (CENC) researchers are reviewed. COVID-19's effects on the conduct of LIMBIC-CENC for the short-term and long-term were considered to ensure the study continued safely for participants and researchers. COVID-19 may have long-lasting health and especially neurological effects which may confound the quantitative and qualitative measures of this any comparable longitudinal studies. The recognition, understanding, and preparation of COVID-19's impact on a longitudinal military and veteran mTBI population is crucial to successfully conducting LIMBIC-CENC and similar neurological research studies. Developing a plan based on the best available information while remaining agile as new information about COVID-19 emerge, is essential. Research presented in this special issue underscores the complexity of studying long-term effects of mTBI, in a population exposed to and symptomatic from COVID-19.

Heterogeneity of health-related quality of life after mild traumatic brain injury with systemic injury: a cluster analytic approach

Purpose Health-related quality of life (HRQoL) is a key component of evaluating outcome after mild traumatic brain injury (mTBI). As outcome is heterogeneous following mTBI, it is relevant to examine individual differences in HRQoL. This study investigated whether multiple homogenous subgroups could be meaningfully identified, 10 weeks after hospitalised mTBI with systemic injury, on the basis of HRQoL profiles. Methods Ninety-one adults were assessed for HRQoL, pain, fatigue, sleep quality, psychological distress, cognition and post-concussion symptoms. Results Cluster analyses revealed three separate subgroups based on physical, mental, social and energy HRQoL. One group (42%) demonstrated normative levels of HRQoL on all subdomains. The remaining two groups demonstrated significantly reduced HRQoL on all subdomains. These groups had equivalently poor mental, social and energy HRQoL, but the smallest group (27%) had significantly poorer physical HRQoL. Multinomial logistic regression revealed that pain significantly and independently predicted group membership for the particularly poor physical HRQoL group. Fatigue was the only significant independent predictor of group membership for the remaining group with reduced HRQoL. Conclusion These findings suggest more than 50% of hospitalised individuals with mTBI and systemic injury, have reduced HRQoL, 10 weeks after mTBI. Pain and fatigue warrant clinical attention in these individuals. IMPLICATIONS FOR REHABILITATION Mild traumatic brain injury is a common event that has been shown to be associated with persistently reduced health-related quality of life in approximately 50% of individuals 6 to 12 months after injury. Health-related quality of life likely varies between individuals after injury Relative to the “normal” population, most individuals in this cohort of individuals with mTBI and systemic injury had reduced mental, social and energy quality of life 10 weeks after injury. Fatigue and pain are important factors in reduced health-related quality of life after mTBI with systemic injury. Further research is needed to determine whether these fatigue and pain issues are related to mTBI-factors, such as headache, and/or related to systemic injury factors, which are common in the mTBI population.

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.

Clinical Practice Guideline Recommendations in Pediatric Mild Traumatic Brain Injury: A Systematic Review

Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.

74 Construct Validity for the Automatized Sequencing Test (AST) in Hispanic/Latino and Bilingual Youth

Objective:Adequate effort by examinees during neurocognitive testing is a prerequisite to valid interpretation of test results. Utilizing performance validity tests (PVTs) is strongly recommended within pediatric mild Traumatic Brain Injury (mTBI) populations. PVTs have historically been created based on majority-white and monolingual groups; investigating their validity in additional patient populations remains essential. The Automatized Sequencing Task (AST) was developed as a brief validity measure within mTBI youth (Kirkwood, et.al., 2014). This study aimed to examine the clinical utility of the AST among youth identifying as Hispanic/Latino and/or bilingual within a mTBI clinical sample.Participants and Methods:Participants ages 8-17 (N=103, M age=14.08, SD=2.2, 51.5% male, 42.7% Hispanic/Latino, 23.6% bilingual) were drawn from an outpatient mTBI/concussion program within the past 2.6 years. Median time of evaluation since injury was 3.7 weeks. Eligibility criteria included: 1) evaluated for a mTBI (GCS . 13) and 2) 8 through 17 years of age. Language status included English only and English-Spanish bilingual youth. Of the bilingual youth, 95% were considered English dominant. Youth were timed while reciting four well-learned (i.e., automatized) sequences as rapidly as possible: 1) the alphabet, 2) counting from 1-20, 3) the days of the week, and 4) the months of the year. Pass rates for the AST were examined using chi-square tests to compare performance based on ethnic/cultural identity (Hispanic vs Non-Hispanic), language status, age (children 8-12; teens 13-17), and gender.Results:In the clinical sample, 11.7% (n=12) could not complete AST months; 75% of non-completers were Hispanic/Latino. Participants who identified as Hispanic/Latino compared to Non-Hispanic/Latino participants were significantly more likely to fail the 4-item AST, χ2(1) =4.3, p<.05. The odds of failing the 4-item AST was 2.3 times higher if patients identified as Hispanic/Latino. Further, patients identifying as bilingual were even more likely to fail the 4-item AST, χ2(1) =4.5, p<.05. The odds of failing the 4-item AST was 3.0 times higher if patients were bilingual. There were no ethnicity or bilingual group differences in AST failure when examining performance on the 3-item AST. Neither age nor gender were a significant predictor of failure on the 3-item or 4-item AST.Conclusions:Results suggest that the month item on the AST does not function consistently across Hispanic/Latino and bilingual youth. It cannot be presumed to be ‘automatic’ as a significant number of Hispanic/Latino and/or bilingual patients were unable to complete the month item, but with otherwise intact performance on the first three items. Administering only the first three items on the AST appears to be a more culturally sensitive alternative given the increased odds of 4-item failure in Hispanic/Latino and bilingual youth. Additional research is needed to explore the predictive validity of the AST as a PVT in varying ethnic, culturally, linguistically, and socioeconomically diverse mTBI pediatric populations.

A - 135 The Relationship between Executive Functioning and Psychological Outcomes Post Mild Traumatic Brain Injury.

Cognitive outcomes post mTBI are well-researched, but the relationship between executive functioning and psychiatric outcomes have received much less attention. This study explored emotional outcomes of individuals who sustained a mTBI and the potential relationship to executive functioning. A research study by Zainal & Newman (2021) found that older adults with severe depression and anxiety experienced increased inflammation, which potentially resulted in reduced executive functioning. mTBI is also associated with inflammation - potentially providing a compound effect or interaction. Additional research is needed to clarify the potential compound impact of mTBI and depression and anxiety might have upon cognition. 185 individuals were extracted from an archival clinical database of neuropsychological evaluations of individuals noting deficits following mTBI. Executive functioning was measured using Trail Making Test B (TMT-B). Emotional distress was assessed using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). A Multiple Linear Regression was used to assess the impact of emotional distress (BAI and BDI) upon executive functioning performance (TMT-B) in this population. Regression analysis identified a relationship between emotional distress upon executive functioning that approached significance (p = 0.057; r^2 = 0.031). These findings are consistent with previous literature suggesting a modest relationship between emotional distress and executive functioning - this time in a sample with mTBI population. Specific injury, resilience, and other confounding factors to clarify the actual risk and relationship is warranted.

A - 143 Factor Structure of the Beck Anxiety Inventory in Mild Traumatic Brain Injury.

The Beck Anxiety Inventory-II (BAI) is a widely used screening instrument for anxiety symptoms in clinical and medical populations. The factor structure of the BAI remains unknown for people with mild traumatic brain injury (mTBI), despite common anxiety symptoms in this group. This study compared one, two, and four-factor models of the BAI in an mTBI sample. A sample of 141 individuals diagnosed with an mTBI were evaluated. All subjects were administered the BAI screening measure during a comprehensive neuropsychological evaluation in a private practice setting. Confirmatory factor analysis was used to test whether items loaded on a single anxiety factor, a two-factor structure with a somatic-affective and cognitive component of anxiety (based on original BAI), or a four-factor structure derived from studies in other populations with cognitive impairments. The sample was predominantly female (63%), with a mean age of 46.93 (SD = 13.28) and a mean education level of 15.08 (SD = 2.65). Consistent with prior literature, 69% of our sample reported at least mild symptoms of anxiety (BAI > 8). Confirmatory factor analysis (CFA) results indicated the best fit was the model with four factors consisting of cognitive, autonomic, neuromotor, and panic symptoms, CFI = 0.92; RMSEA = 0.067, 90% CI (0.053,0.081). These results suggest that instead of the two-factor model posited by original creators of the BAI, clinicians and researchers should attend to four clusters of anxiety symptoms in mTBI populations. Anxiety symptoms following mTBI can be evaluated based on cognitive, autonomic, neuromotor, and panic components.

Exercise Intolerance After Mild Traumatic Brain Injury Occurs in All Subtypes in the Adult Population.

Thematically grouped symptom clusters are present during the acute timeline of post-mild traumatic brain injuries (mTBI), representing clinical profiles called subtypes. Exercise intolerance has not been evaluated within the subtype classifications and, because guidelines support early submaximal aerobic exercise, further knowledge is required in regard to the exercise capabilities among the concussion subtypes. This cross-sectional study (n = 78) aimed to characterize the presence of exercise intolerance within the clinical subtypes and to explore performance on the Buffalo Concussion Treadmill Test (BCTT) in the adult subacute (2-12 weeks post-injury) mTBI population. All participants were evaluated using the BCTT to determine exercise tolerance. We first used the Neurobehavioral Symptom Inventory (NSI) questionnaire to assign each participant a primary subtype(s). To further explore all five subtypes (headache, cognitive, vestibular, ocular motor, and mood), participants were assessed using a multitude of thematically grouped assessments including self-reported questionnaires, clinical tests of vestibular and ocular motor function, balance function, and computerized cognitive testing. Thirty-seven (47%) subjects were exercise tolerant and 41 (53%) were exercise intolerant. There was no difference in the distribution of primary subtypes between the exercise tolerant and exercise intolerant groups. In addition, no significant differences were found between the exercise tolerant and exercise intolerant groups on other thematically grouped subtype assessments. The exercise intolerant group had a significantly higher resting heart rate (HR), lower percentage of age-predicted maximum HR achieved, lower Borg Rate of Perceived Exertion (RPE), and could walk on the treadmill for less time (lower duration) compared with the exercise tolerant group. The current findings suggest that exercise intolerance is common and pervasive across all five mTBI subtypes. A comprehensive mTBI assessment should include evaluation for exercise intolerance regardless of the primary clustering of symptoms and across patient populations. Therefore, early referral to physical therapists, athletic trainers, or medical clinics that can perform the BCTT may be helpful to initiate appropriate exercise prescriptions for patients with mTBI.

Clinical predictors of abnormal brain computed tomography findings in mild traumatic brain injury: A cross-sectional study.

Mild traumatic brain injury (mTBI) is a health challenge world widely. Local evidence is essential to establish decision-making algorithms. According to the lack of sufficient evidence, the present study aimed to investigate the epidemiology of mTBI and predictive factors of abnormal brain computed tomography (CT) scans. The present analytical cross-sectional study was conducted between March 2021 to September 2022 on patients with the diagnosis of mTBI. Subjects were individuals who were diagnosed with mTBI in 2 Level I trauma centers located in Isfahan province, which serves as the referral center for the entire population of the province. Demographic and clinical data were recorded during a face-to-face interview. The brain CT scans were interpreted by an experienced radiologist. Data were analyzed using IBM SPSS Statistics for Mac, Version 24.0. 498 patients were enrolled in the study, consisting of 393 (78.9%) men and 65 (13.1%) children younger than 10 years old. 100 (20%) of them had abnormal CT scan findings. The mean age of participants was 33.39 ± 19.69, which was significantly higher in patients who had abnormal CT scans (P value = .002). Despite the most common mechanism in both groups being motor accidents, the rate of motor accidents was higher in patients with abnormal findings of CT scan (P value = .048). Multiple logistic regression revealed that post-traumatic vomiting (PTV) (odd ratios [OR]: 3.736), post-traumatic amnesia (PTA) (OR:3.613), raccoon eyes (OR:47.878), and Glasgow coma scale (GCS) of 15 (OR:0.11) are predictive factors for abnormal findings. The present study suggested the presence of PTV, PTA, raccoon eyes and GCS of 13 or 14 as predictive factors for abnormal findings in mTBI populations.

Prevalence ofNeck Pain inSoldiers as a Result ofMild Traumatic Brain Injury-Associated Trauma.

Many of the injury mechanisms that cause mild traumatic brain injury (mTBI) also create forces commonly associated with whiplash, resulting in cervical pain injury. The prevalence of associated neck pain with mTBI is not well established. There is a strong indication that injury to the cervical spine may aggravate, cause, and/or impact recovery of symptoms and impairments associated with the concussive event and its primary effect on the brain. The purpose of this study is to help identify the prevalence of ensuing cervical pain within 90 days of a previously documented mTBI and to examine the role of neck pain during concurrent concussive symptoms, in a military population stationed at a large military installation. This retrospective design utilized a de-identified dataset using predetermined search and filter criteria, which included male active duty service members (SMs), 20 to 45 years of age, who received medical care at any clinic on Fort Liberty (Fort Bragg, NC) during fiscal year (FY) 2012 to FY 2019, with documented cervicalgia and mTBI (via the International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes), verified using electronic medical records. The final dataset served as the basis for subject sampling and was analyzed to determine the total number of documented cervicalgia and mTBI diagnoses. Results are presented as descriptive statistics. Approval for this study was received from the Andrews University Office of Research (18-097) and the Womack Army Medical Center Human Protections Office. Between FY 2012 and FY 2019, 14,352 unique SMs accessed a Fort Bragg, NC health care facility, at least once(TableI). Overall, 52% of SMs diagnosed with cervicalgia were found to have a previously diagnosed mTBI during the 90 days before the cervicalgia diagnosis. In contrast, the prevalence of same-day cervicalgia and mTBI diagnosis was <1% (TableIV). The prevalence of isolated cervicalgia diagnosis at any time during the reporting period was 3%, whereas isolated mTBI diagnosis was 1% (TableIII). Over 50% of SMs diagnosed with cervicalgia had sustained a documented mTBI within 90 days prior, whereas less than 1% were diagnosed with cervicalgia at the time of initial primary care or emergency room encounter following the mTBI event. This finding suggests that the close anatomical and neurophysiological connections between the head and the cervical spine are both likely to be impacted through the same mechanism of injury. Delayed evaluation (and treatment) of the cervical spine may contribute to lingering post-concussive symptoms. Limitations of this retrospective review include the inability to assess the causality of the relationship between neck pain and mTBI, as only the existence and strength of the prevalence relationship can be identified. The outcome data are exploratory and intended to identify relationships and trends that may suggest further study across installations and across mTBI populations.

Inflammatory cytokines associated with mild traumatic brain injury and clinical outcomes: a systematic review and meta-analysis.

Mild traumatic brain injuries (mTBIs) trigger a neuroinflammatory response, which leads to perturbations in the levels of inflammatory cytokines, resulting in a distinctive profile. A systematic review and meta-analysis were conducted to synthesize data related to levels of inflammatory cytokines in patients with mTBI. The electronic databases EMBASE, MEDLINE, and PUBMED were searched from January 2014 to December 12, 2021. A total of 5,138 articles were screened using a systematic approach based on the PRISMA and R-AMSTAR guidelines. Of these articles, 174 were selected for full-text review and 26 were included in the final analysis. The results of this study demonstrate that within 24 hours, patients with mTBI have significantly higher levels of Interleukin-6 (IL-6), Interleukin-1 Receptor Antagonist (IL-1RA), and Interferon-γ (IFN-γ) in blood, compared to healthy controls in majority of the included studies. Similarly one week following the injury, patients with mTBI have higher circulatory levels of Monocyte Chemoattractant Protein-1/C-C Motif Chemokine Ligand 2 (MCP-1/CCL2), compared to healthy controls in majority of the included studies. The results of the meta-analysis also confirmed these findings by demonstrating significantly elevated blood levels of IL-6, MCP-1/CCL2, and Interleukin-1 beta (IL-1β) in the mTBI population compared to healthy controls (p < 0.0001), particularly in the acute stages (<7 days). Furthermore, it was found that IL-6, Tumor Necrosis Factor-alpha (TNF-α), IL-1RA, IL-10, and MCP-1/CCL2 were associated with poor clinical outcomes following the mTBI. Finally, this research highlights the lack of consensus in the methodology of mTBI studies that measure inflammatory cytokines in the blood, and also provides direction for future mTBI research.

Investigation of neurobiological responses to theta burst stimulation during recovery from mild traumatic brain injury (mTBI)

ObjectiveThe ability of the brain to recover following neurological insult is of interest for mild traumatic brain injury (mTBI) populations. Investigating whether non-invasive brain stimulation (NIBS) can modulate neurophysiology and cognition may lead to the development of therapeutic interventions post injury. The purpose of this study was to investigate neurobiological effects of one session of intermittent theta burst stimulation (iTBS) to the dorsolateral prefrontal cortex (DLPFC) in participants recovering from mTBI. MethodChanges to neurophysiology were assessed with electroencephalography (EEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG). Digit span working memory accuracy assessed cognitive performance. 30 patients were assessed within one-month of sustaining a mTBI and 26 demographically matched controls were assessed. Participants were also assessed at 3-months (mTBI: N = 21, control: N = 26) and 6-months (mTBI: N = 15, control: N = 24). ResultsAnalyses demonstrated iTBS did not reliably modulate neurophysiological activity, and no differences in cognitive performance were produced by iTBS at any assessment time-point. ConclusionsFactors responsible for our null results are unclear. Possible limitations to our experimental design are discussed. SignificanceOur findings suggest additional research is required to establish the effects of iTBS on plasticity following mTBI, prior to therapeutic application. Data and Code Availability StatementWe do not have ethical approval to make this data publicly available, as our approval predated our inclusion of such approvals (which we now do routinely).

Assessment of balance in people with mild traumatic brain injury using a balance systems model approach

PurposeMeasuring persistent imbalance after mTBI is challenging and may include subjective symptom-reporting as well as clinical scales. Clinical assessments for quantifying balance following mTBI have focused on sensory orientation. It is theorized that balance control goes beyond sensory orientation and also includes subdomains of anticipatory postural adjustments, reactive postural control, and dynamic gait. The Mini Balance Evaluation Systems Test (Mini-BESTest) is a validated balance test that measures balance according to these subdomains for a more comprehensive assessment. The purpose of this study was to compare Mini-BESTest total and subdomain scores after subacute mTBI with healthy controls. MethodsSymptomatic mTBI (n = 90, 20 % male, age=36.0 ± 12.0, 46.3.4 ± 22.1 days since injury) and healthy control (n = 45, 20 % male, age=35.4 ± 12.5) participants completed the Mini-BESTest for balance. Mini-BESTest between-group differences were evaluated using Wilcoxon rank-sum tests. ResultsThe mTBI group (Median[minimum,maximum]) had a significantly worse Mini-BESTest total score than the healthy controls (24[18,28] vs 27[23–28], p < 0.001). The mTBI group performed significantly worse in 3 of the 4 subdomains compared to the healthy controls: reactive postural control: 5[2–6] vs 6[3–6], p = 0.003; sensory orientation: 6[5,6] vs 6[6], p = 0.005; dynamic gait: 8[5–10] vs 9[8–10], p < 0.001. There was no significance difference between groups in the anticipatory postural adjustments domain (5[3–6] vs 5[3–6], p = 0.12). ConclusionsThe Mini-BESTest identified deficits in people with subacute mTBI in the total score and 3 out of 4 subdomains, suggesting it may be helpful to use in the clinic to identify balance subdomain deficits in the subacute mTBI population. In combination with self-reported assessments, the mini-BESTest may identify balance domain deficits in the subacute mTBI population and help guide treatment for this population.

Comparing resting-state connectivity of working memory networks in U.S. Service members with mild traumatic brain injury and posttraumatic stress disorder

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are prevalent among military populations, and both have been associated with working memory (WM) impairments. Previous resting-state functional connectivity (rsFC) research conducted separately in PTSD and mTBI populations suggests that there may be similar and distinct abnormalities in WM-related networks. However, no studies have compared rsFC of WM brain regions in participants with mTBI versus PTSD. We used resting-state fMRI to investigate rsFC of WM networks in U.S. Service Members (n = 127; ages 18–59) with mTBI only (n = 46), PTSD only (n = 24), and an orthopedically injured (OI) control group (n = 57). We conducted voxelwise rsFC analyses with WM brain regions to test for differences in WM network connectivity in mTBI versus PTSD. Results revealed reduced rsFC between ventrolateral prefrontal cortex (vlPFC), lateral premotor cortex, and dorsolateral prefrontal cortex (dlPFC) WM regions and brain regions in the dorsal attention and somatomotor networks in both mTBI and PTSD groups versus controls. When compared to those with mTBI, individuals with PTSD had lower rsFC between both the lateral premotor WM seed region and middle occipital gyrus as well as between the dlPFC WM seed region and paracentral lobule. Interestingly, only vlPFC connectivity was significantly associated with WM performance across the samples. In conclusion, we found primarily overlapping patterns of reduced rsFC in WM brain regions in both mTBI and PTSD groups. Our finding of decreased vlPFC connectivity associated with WM is consistent with previous clinical and neuroimaging studies. Overall, these results provide support for shared neural substrates of WM in individuals with either mTBI or PTSD.

0625 Characterization of Obstructive Sleep Apnea in Active-Duty US Military Personnel Receiving Interdisciplinary Care at the National Intrepid Center of Excellence

Abstract Introduction Among active-duty service members (ADSMs), obstructive sleep apnea (OSA) is associated with decreased quality of life and military readiness/retention. Limited evidence suggests mild traumatic brain injury (mTBI) patients have increased OSA incidence, but little is known about the underlying physiology. This study aims to characterize OSA in treatment-seeking ADSMs with a history of remote mTBI and/or persistent neurobehavioral symptoms to improve detection and early intervention. Methods This is a retrospective analysis of data collected from ADSMs attending the National Intrepid Center of Excellence Intensive Outpatient Program for persistent symptoms associated with mTBI. Sleep assessment included overnight polysomnography and self-report assessments of sleep quality, somatic and mood symptoms. OSA severity was determined by apnea-hypopnea index (negative: &amp;lt;5, mild: 5-15, moderate/severe: ≥15). Group differences were assessed using analysis of covariance and pairwise least squares regression, controlling for age and body mass index, and corrected for multiple comparisons. Results Analyses included 574 ADSMs, mostly male (99%), with a mean age of 39.7. The majority (n=288; 50.2%) were OSA negative (OSA-neg); a third had mild OSA (m-OSA) (n=216; 38%); and a tenth were diagnosed with moderate/severe OSA (mod/s-OSA) (n=70; 12%). Mod/s-OSA patients had increased arousal index (p&amp;lt;0.01), hypoxia time (p&amp;lt;0.001), reduced total sleep time (p&amp;lt;0.01) and sleep efficiency (p&amp;lt;0.001) compared to m-OSA and OSA-neg patients. M-OSA patients had an increased arousal index compared to OSA-neg patients (p&amp;lt;0.01). Patient groups did not significantly differ on subjective measures of sleep (i.e., quality, sleepiness), post-concussive, or behavioral health symptoms (anxiety, depression, post-traumatic stress symptoms, alcohol misuse). Conclusion In our sample of treatment-seeking ADSMs, nearly half presented with OSA according to cut-scores derived for AHI, greater than that expected in the general population. As reported in civilian populations, mod/s-OSA patients demonstrated worse objective sleep measures compared to m-OSA and OSA-neg patients, yet in our sample their self-reported symptom severity did not differ. These findings suggest a low threshold for OSA screening is needed in the symptomatic mTBI population and that multiple factors other than OSA likely contribute to perceived sleep disturbances and neurobehavioral symptoms. Support (If Any) None.

Sensory Phenotypes for Balance Dysfunction After Mild Traumatic Brain Injury.

Recent team-based models of care use symptom subtypes to guide treatments of individuals with chronic effects of mild traumatic brain injury (mTBI). However, these subtypes, or phenotypes, may be too broad, particularly for balance (e.g., vestibular subtype). To gain insight into mTBI-related imbalance, we (1) explored whether a dominant sensory phenotype (e.g., vestibular impaired) exists in the chronic mTBI population, (2) determined the clinical characteristics, symptomatic clusters, functional measures, and injury mechanisms that associate with sensory phenotypes for balance control in this population, and (3) compared the presentations of sensory phenotypes between individuals with and without previous mTBI. A secondary analysis was conducted on the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. Sensory ratios were calculated from the sensory organization test, and individuals were categorized into 1 of the 8 possible sensory phenotypes. Demographic, clinical, and injury characteristics were compared across phenotypes. Symptoms, cognition, and physical function were compared across phenotypes, groups, and their interaction. Data from 758 Service Members and Veterans with mTBI and 172 individuals with no lifetime history of mTBI were included. Abnormal visual, vestibular, and proprioception ratios were observed in 29%, 36%, and 38% of people with mTBI, respectively, with 32% exhibiting more than 1 abnormal sensory ratio. Within the mTBI group, global outcomes (p < 0.001), self-reported symptom severity (p < 0.027), and nearly all physical and cognitive functioning tests (p < 0.027) differed across sensory phenotypes. Individuals with mTBI generally reported worse symptoms than their non-mTBI counterparts within the same phenotype (p = 0.026), but participants with mTBI in the vestibular-deficient phenotype reported lower symptom burdens than their non-mTBI counterparts (e.g., mean [SD] Dizziness Handicap Inventory = 4.9 [8.1] for mTBI vs 12.8 [12.4] for non-mTBI, group × phenotype interaction p < 0.001). Physical and cognitive functioning did not differ between the groups after accounting for phenotype. Individuals with mTBI exhibit a variety of chronic balance deficits involving heterogeneous sensory integration problems. While imbalance when relying on vestibular information is common, it is inaccurate to label all mTBI-related balance dysfunction under the vestibular umbrella. Future work should consider specific classification of balance deficits, including specific sensory phenotypes for balance control.

Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review.

Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9–213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.

Prevalence of depression and anxiety disorders following mild traumatic brain injury.

Previous studies have identified an association between traumatic brain injuries and the development of psychiatric disorders in general. However, these studies were subject to limitations that demonstrate the need for a study of a large, clearly defined mild traumatic brain injury (mTBI) population within an integrated healthcare system. To determine the prevalence and relative risk of postinjury affective disorders over 4 years following mTBI. Cohort study of mTBI cases and matched controls, over a 4-year period. An integrated healthcare delivery system in California. A total of 9428 adult health plan members diagnosed with mTBI from 2000-2007 and enrolled in the year before injury, during which no TBI was ascertained. Control participants included 18,856 individuals selected based on the following criteria: Two unexposed health plan members per each mTBI-exposed patient were randomly selected and individually matched for age, gender, race/ethnicity, and medical comorbidities. Not applicable. A diagnosis of affective disorder (depressive, anxiety, and adjustment disorders) in the 4 years after mTBI or the reference date, determined according to the International Classification of Diseases, Ninth Revision, Clinical Modification as well as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Affective disorders were most prominent during the first 12 months with 23% following mTBI and 14% in the control group. Four-year aggregate adjusted odds ratios for having an affective disorder following mTBI were 1.2 (95% CI: 1.1, 1.2; p < .001) and 1.5 (95% CI: 1.5, 1.6; p < .001) for patients with and without prior affective disorders, respectively. mTBI was associated with a significantly increased risk of having subsequent affective disorders. Screening for and addressing affective disorders at earlier stages following the injury is an important step to avoid persisting conditions that may pose a barrier to full recovery.

801 Obstructive Sleep Apnea Symptoms Predict Cognitive Function Following Mild Traumatic Brain Injury

Abstract Introduction Sleep disturbances are commonly reported following mild traumatic brain injury (mTBI). Specifically, one of these disturbances is obstructive sleep apnea (OSA), which involves repeated episodes of reduced upper-airway flow during sleep. When compared to the general population, OSA is reported at a much higher rate among the mTBI population. However, little research has investigated the relationship between OSA and cognitive performance among the mTBI population. We predicted that in those who suffered a mTBI, symptoms of sleep apnea would be predictive lower cognitive processing. Methods We collected data from 37 healthy controls (Mean age = 24.3 □ 5.8) and 145 participants with mTBI (Mean age = 24.3 □ 6.8), ranging from 2 weeks to 12 months post-injury. Participants completed the Pittsburg Sleep Quality Index (PSQI) including questions indicative of OSA, such as “cannot breathe comfortably” and “cough or snore loudly” during sleep. We calculated the PSQI Sleep Disturbance (PSQI-SD) composite score, which ranged from 0 to 2. Participants completed the Automated Neuropsychological Assessment Metrics (ANAM4), a novel computer-based assessment, to measure reaction time (RT). Results When comparing the percentage of participants in each group endorsing sleep disturbances on the PSQI-SD, we found a significant difference in the proportion of individuals scoring a 2 on PSQI-SD between the groups (□2(2) = 13.55, p = .001). In healthy controls, 8% scored 0, 89% scored 1, and 3% scored 2 on the PSQI-SD. In contrast, following mTBI, 1.4% scored 0, 72.4% scored 1, and 26.2% scored 2 on the PSQI-SD. Furthermore, PSQI-SD significantly predicted RT (□ = .18, p = .03) in the mTBI group, a relationship not observed in the control group (□ = .30, p = .07). Conclusion mTBI increases the incidence of sleep disturbances and symptoms related to OSA. Furthermore, sleep disturbances and OSA-related symptoms were predictive of cognitive performance in individuals who sustained a mTBI, but not healthy controls. Increases in PSQI-SD scores were associated with increased RT, indicating greater deficits in cognitive function, specifically reaction time. These data provide evidence that higher severity in respiratory symptoms relating to sleep apnea hinders cognitive processing, particularly for individuals who have suffered a mTBI. Support (if any):