Neural Mechanisms Associated With Postural Control in Collegiate Soccer and Non-Soccer Athletes.

BACKGROUND AND PURPOSE: Sport-specific training may improve postural control, while repetitive head acceleration events (RHAEs) may compromise it. Understanding the neural mechanisms underlying postural control may contextualize changes due to training and RHAE. The goal of this study was to determine whether postural sway during the Balance Error Scoring System (BESS) is related to white matter organization (WMO) in collegiate athletes. METHODS: Collegiate soccer (N = 33) and non-soccer athletes (N = 44) completed BESS and diffusion tensor imaging. Postural sway during each BESS stance, fractional anisotropy (FA), and mean diffusivity (MD) were extracted for each participant. Partial least squares analyses determined group differences in postural sway and WMO and the relationship between postural sway and WMO in soccer and non-soccer athletes separately. RESULTS: Soccer athletes displayed better performance during BESS 6, with lower FA and higher MD in the medial lemniscus (ML) and inferior cerebellar peduncle (ICP), compared to non-soccer athletes. In soccer athletes, lower sway during BESS 2, 5, and 6 was associated with higher FA and lower MD in the corticospinal tract, ML, and ICP. In non-soccer athletes, lower sway during BESS 2 and 4 was associated with higher FA and lower MD in the ML and ICP. BESS 1 was associated with higher FA, and BESS 3 was associated with lower MD in the same tracts in non-soccer athletes. DISCUSSION AND CONCLUSIONS: Soccer and non-soccer athletes showed unique relationships between sway and WMO, suggesting that sport-specific exposures are partly responsible for changes in neurological structure and accompanying postural control performance and should be considered when evaluating postural control after injury.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A472).

ENIGMA's simple seven: Recommendations to enhance the reproducibility of resting-state fMRI in traumatic brain injury.

Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

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

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Intimate Partner Violence-Related Brain Injury: Unmasking and Addressing the Gaps.

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

Novel Oppositional Defiant Disorder or Conduct Disorder 24 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI). METHODS: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury. RESULTS: Of the children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified who were recruited in this study, 165 were included in this sample; 95 of these children returned for the 24-month assessment. Multiple imputation was used to address attrition. The prevalence of novel oppositional defiant disorder or conduct disorder was 23.7 out of 165 (14%). In univariable analyses, novel oppositional defiant disorder or conduct disorder was significantly associated with psychosocial adversity (p=0.049) and frontal white matter lesions (p=0.016) and was marginally but not significantly associated with SES. In the final multipredictor model, frontal white matter lesions were significantly associated with novel oppositional defiant disorder or conduct disorder (p=0.021), and psychosocial adversity score was marginally but not significantly associated with the outcome. The odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel depressive disorder was significantly higher for girls than boys (p=0.025), and the odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel attention-deficit hyperactivity disorder (ADHD) was significantly higher for boys than girls (p=0.006). CONCLUSION: Approximately 14% of children with TBI developed oppositional defiant disorder or conduct disorder. The risk for novel oppositional defiant disorder or conduct disorder can be understood from a biopsychosocial perspective. Sex differences were evident for comorbid novel depressive disorder and comorbid novel ADHD.

Neurological Effects of Repeated Blast Exposure in Special Operations Personnel.

Exposure to blast overpressure has been a pervasive feature of combat-related injuries. Studies exploring the neurological correlates of repeated low-level blast exposure in career "breachers" demonstrated higher levels of tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 and decreases in IL-10 within brain-derived extracellular vesicles (BDEVs). The current pilot study was initiated in partnership with the U.S. Special Operations Command (USSOCOM) to explore whether neuroinflammation is seen within special operators with prior blast exposure. Data were analyzed from 18 service members (SMs), inclusive of 9 blast-exposed special operators with an extensive career history of repeated blast exposures and 9 controls matched by age and duration of service. Neuroinflammation was assessed utilizing positron emission tomography (PET) imaging with [18F]DPA-714. Serum was acquired to assess inflammatory biomarkers within whole serum and BDEVs. The Blast Exposure Threshold Survey (BETS) was acquired to determine blast history. Both self-report and neurocognitive measures were acquired to assess cognition. Similarity-driven Multi-view Linear Reconstruction (SiMLR) was used for joint analysis of acquired data. Analysis of BDEVs indicated significant positive associations with a generalized blast exposure value (GBEV) derived from the BETS. SiMLR-based analyses of neuroimaging demonstrated exposure-related relationships between GBEV, PET-neuroinflammation, cortical thickness, and volume loss within special operators. Affected brain networks included regions associated with memory retrieval and executive functioning, as well as visual and heteromodal processing. Post hoc assessments of cognitive measures failed to demonstrate significant associations with GBEV. This emerging evidence suggests neuroinflammation may be a key feature of the brain response to blast exposure over a career in operational personnel. The common thread of neuroinflammation observed in blast-exposed populations requires further study.

Microstructural Organization of Distributed White Matter Associated With Fine Motor Control in US Service Members With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = 190) underwent magnetic resonance imaging and the GPB test. We first examined between-group differences in GPB completion time. We then investigated associations between GPB performance and regional structural imaging measures (tractwise diffusivity, subcortical volumes, and cortical thickness) in SM&Vs with a history of mTBI(s). Lastly, we explored whether mTBI history moderated associations between imaging measures and GPB performance. SM&Vs with mTBI(s) performed worse than those without mTBI(s) on the non-dominant hand GPB test at a trend level (p < 0.1). Higher fractional anisotropy (FA) of tracts including the posterior corona radiata, superior longitudinal fasciculus, and uncinate fasciculus were associated with better GPB performance in the dominant hand in SM&Vs with mTBI(s). These findings support that the organization of several white matter bundles are associated with fine motor performance in SM&Vs. We did not observe that mTBI history moderated associations between regional FA and GPB test completion time, suggesting that chronic mTBI may not significantly influence fine motor control.

Higher order neurocognition in pediatric brain tumor survivors: What can we learn from white matter microstructure?

BACKGROUND: Pediatric brain tumor survivors (PBTS) experience neurocognitive late effects, including problems with working memory, processing speed, and other higher order skills. These skill domains are subserved by various white matter (WM) pathways, but not much is known about these brain-behavior links in PBTS. This study examined the anterior corona radiata (ACR), inferior fronto-occipital fasciculi (IFOF), and superior longitudinal fasciculi (SLF) by analyzing associations among diffusion metrics and neurocognition. PROCEDURE: Thirteen PBTS and 10 healthy controls (HC), aged 9-14 years, completed performance-based measures of processing speed and executive function, and parents rated their child's day-to-day executive skills. Children underwent magnetic resonance imaging (MRI) with diffusion weighted imaging that yielded fractional anisotropy (FA) and mean diffusivity (MD) values. Independent samples t-tests assessed group differences on neurocognitive and imaging measures, and pooled within-group correlations examined relationships among measures across groups. RESULTS: PBTS performed more poorly than HC on measures of processing speed, divided attention, and shifting (d = -1.08 to -1.44). WM microstructure differences were significant in MD values for the bilateral SLF and ACR, with PBTS showing higher diffusivity (d = 0.75 to 1.21). Better processing speed, divided attention, and shifting were associated with lower diffusivity in the IFOF, SLF, and ACR, but were not strongly correlated with FA. CONCLUSIONS: PBTS demonstrate poorer neurocognitive functioning that is linked to differences in WM microstructure, as evidenced by higher diffusivity in the ACR, SLF, and IFOF. These findings support the use of MD in understanding alterations in WM microstructure in PTBS and shed light on potential functions of these pathways.

Phenotyping Depression After Mild Traumatic Brain Injury: Evaluating the Impact of Multiple Injury, Gender, and Injury Context.

The chronic mental health consequences of mild traumatic brain injury (TBI) are a leading cause of disability. This is surprising given the expectation of significant recovery after mild TBI, which suggests that other injury-related factors may contribute to long-term adverse outcomes. The objective of this study was to determine how number of prior injuries, gender, and environment/context of injury may contribute to depressive symptoms after mild TBI among deployed United States service members and veterans (SMVs). Data from the Long-term Impact of Military-Relevant Brain Injury Consortium Prospective Longitudinal Study was used to assess TBI injury characteristics and depression scores previously measured on the Patient Health Questionnaire-9 (PHQ-9) among a sample of 1456 deployed SMVs. Clinical diagnosis of mild TBI was defined via a multi-step process centered on a structured face-to-face interview. Logistical and linear regressions stratified by gender and environment of injury were used to model depressive symptoms controlling for sociodemographic and combat deployment covariates. Relative to controls with no history of mild TBI (n = 280), the odds ratios (OR) for moderate/severe depression (PHQ-9 ≥ 10) were higher for SMVs with one mild TBI (n = 358) OR: 1.62 (95% confidence interval [CI] 1.09-2.40, p = 0.016) and two or more mild TBIs (n = 818) OR: 1.84 (95% CI 1.31-2.59, p < 0.001). Risk differences across groups were assessed in stratified linear models, which found that depression symptoms were elevated in those with a history of multiple mild TBIs compared with those who had a single mild TBI (p < 0.001). Combat deployment-related injuries were also associated with higher depression scores than injuries occurring in non-combat or civilian settings (p < 0.001). Increased rates of depression after mild TBI persisted in the absence of post-traumatic stress disorder. Both men and women SMVs separately exhibited significantly increased depressive symptom scores if they had had combat-related mild TBI. These results suggest that contextual information, gender, and prior injury history may influence long-term mental health outcomes among SMVs with mild TBI exposure.

Subcortical functional connectivity and its association with walking performance following deployment related mild TBI.

Introduction: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred. Methods: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, Service Members and Veterans whose mild TBI occurred outside of deployment, and Service Members and Veterans who had no lifetime history of TBI. Results: FC patterns differed for the two contextual types of mild TBI. Service Members and Veterans with deployment-related mild TBI demonstrated increased FC between the right caudate and lateral occipital regions relative to both the non-deployment mild TBI and TBI-negative groups. When evaluating the association between FC from the caudate and gait, the non-deployment mild TBI group showed a significant positive relationship between walking time and FC with the frontal pole, implicated in navigational planning, whereas the deployment-related mild TBI group trended towards a greater negative association between walking time and FC within the occipital lobes, associated with visuo-spatial processing during navigation. Discussion: These findings have implications for elucidating subtle motor disruption in Service Members and Veterans with deployment-related mild TBI. Possible implications for future walking performance are discussed.

Multimodal Analysis of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning. Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function. Design, Setting, and Participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or healthy controls (some with orthopedic injury) were recruited from trauma centers, clinics, and institutional trauma registries, some of which were followed longitudinally over a period of 0.7 to 1.9 years. Healthy controls were recruited from the surrounding community. Data analysis occurred from October to December 2022. Exposure: Accidental mild complicated-severe TBI (msTBI) for those in the TBI group. Some controls received a diagnosis of orthopedic injury. Main Outcomes and Measures: Volume of 18 cerebellar lobules and vermal regions were estimated from 3-dimensional T1-weighted magnetic resonance imaging (MRI) scans. White matter organization in 28 regions of interest was assessed with diffusion tensor MRI. Executive function was measured by parent-reported scores from the Behavior Rating Inventory of Executive Functioning. Results: A total of 598 children and adolescents (mean [SD] age, 14.05 [3.06] years; range, 5.45-19.70 years; 386 male participants [64.5%]; 212 female participants [35.5%]) were included in the study, with 314 participants in the msTBI group, and 284 participants in the non-TBI group (133 healthy individuals and 151 orthopedically injured individuals). Significantly smaller total cerebellum volume (d = -0.37; 95% CI, -0.52 to -0.22; P < .001) and subregional cerebellum volumes (eg, corpus medullare; d = -0.43; 95% CI, -0.58 to -0.28; P < .001) were observed in the msTBI group. These alterations were primarily seen in participants in the chronic phase (ie, >6 months postinjury) of injury (total cerebellar volume, d = -0.55; 95% CI, -0.75 to -0.35; P < .001). Smaller cerebellum volumes were associated with higher scores on the Behavior Rating Inventory of Executive Functioning Global Executive Composite score (ß = -208.9 mm3; 95% CI, -319.0 to -98.0 mm3; P = .008) and Metacognition Index score (ß = -202.5 mm3; 95% CI, -319.0 to -85.0 mm3; P = .02). In a subset of 185 participants with longitudinal data, younger msTBI participants exhibited cerebellum volume reductions (ß = 0.0052 mm3; 95% CI, 0.0013 to 0.0090 mm3; P = .01), and older participants slower growth rates. Poorer white matter organization in the first months postinjury was associated with decreases in cerebellum volume over time (ß=0.52 mm3; 95% CI, 0.19 to 0.84 mm3; P = .005). Conclusions and Relevance: In this cohort study of pediatric msTBI, our results demonstrated robust cerebellar volume alterations associated with pediatric TBI, localized to the posterior lobe. Furthermore, longitudinal cerebellum changes were associated with baseline diffusion tensor MRI metrics, suggesting secondary cerebellar atrophy. These results provide further understanding of secondary injury mechanisms and may point to new opportunities for intervention.

Relation of Aerobic Activity to Cognition and Well-being in Chronic Mild Traumatic Brain Injury: A LIMBIC-CENC Study.

INTRODUCTION: Because chronic difficulties with cognition and well-being are common after mild traumatic brain injury (mTBI) and aerobic physical activity and exercise (PAE) is a potential treatment and mitigation strategy, we sought to determine their relationship in a large sample with remote mTBI. MATERIALS AND METHODS: The Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study is a national multicenter observational study of combat-exposed service members and veterans. Study participants with positive mTBI histories (n = 1,087) were classified as "inactive" (23%), "insufficiently active" (46%), "active" (19%), or "highly active" (13%) based on the aerobic PAE level. The design was a cross-sectional analysis with multivariable regression. PAE was reported on the Behavioral Risk Factor Surveillance System. Preselected primary outcomes were seven well-validated cognitive performance tests of executive function, learning, and memory: The California Verbal Learning Test-Second Edition Long-Delay Free Recall and Total Recall, Brief Visuospatial Memory Test-Revised Total Recall, Trail-Making Test-Part B, and NIH Toolbox for the Assessment of Neurological Behavior and Function Cognition Battery Picture Sequence Memory, Flanker, and Dimensional Change Card Sort tests. Preselected secondary outcomes were standardized self-report questionnaires of cognitive functioning, life satisfaction, and well-being. RESULTS: Across the aerobic activity groups, cognitive performance tests were not significantly different. Life satisfaction and overall health status scores were higher for those engaging in regular aerobic activity. Exploratory analyses also showed better working memory and verbal fluency with higher aerobic activity levels. CONCLUSIONS: An association between the aerobic activity level and the preselected primary cognitive performance outcome was not demonstrated using this study sample and methods. However, higher aerobic activity levels were associated with better subjective well-being. This supports a clinical recommendation for regular aerobic exercise among persons with chronic or remote mTBI. Future longitudinal analyses of the exercise-cognition relationship in chronic mTBI populations are recommended.

Sensory functions and their relation to balance metrics: a secondary analysis of the LIMBIC-CENC multicenter cohort.

Introduction: Among patients with traumatic brain injury (TBI), balance problems often persist alongside hearing and vision impairments that lead to poorer outcomes of functional independence. As such, the ability to regain premorbid independent gait may be dictated by the level of sensory acuity or processing decrements that are shown following TBI assessment. This study explores the relationships between standardized sensory acuity and processing outcomes to postural balance and gait speed. Methods: Secondary analysis was performed on the Long-Term Impact of Military- Relevant Brain Injury Consortium Chronic Effects of Neurotrauma Consortium LIMBIC (CENC) data set. Separate regression analyses were carried out for each of the balance assessments (via Computerized Dynamic Posturography, CDP) and walking speed. Discussion: TBI frequency was significantly related to the majority of single CDP outcomes (i.e., Conditions 2-6), while various sensory processing outcomes had task-specific influences. Hearing impairments and auditory processing decrements presented with lower CDP scores (CDP Conditions 3,5,6, and 1-3 respectively), whereas greater visual processing scores were associated with better CDP scores for Conditions 2,5, and 6. In sum, patients with TBI had similar scores on static balance tests compared to non-TBI, but when the balance task got more difficult patients with TBI scored worse on the balance tests. Additionally, stronger associations with sensory processing than sensory acuity measures may indicate that patients with TBI have increased fall risk.

Headache among combat-exposed veterans and service members and its relation to mild traumatic brain injury history and other factors: a LIMBIC-CENC study.

Background: Headache (HA) is a common persistent complaint following mild traumatic brain injury (mTBI), but the association with remote mTBI is not well established, and risk factors are understudied. Objective: Determine the relationship of mTBI history and other factors with HA prevalence and impact among combat-exposed current and former service members (SMs). Design: Secondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Methods: We examined the association of lifetime mTBI history, demographic, military, medical and psychosocial factors with (1) HA prevalence ("lately, have you experienced headaches?") using logistic regression and (2) HA burden via the Headache Impact Test-6 (HIT-6) using linear regression. Each lifetime mTBI was categorized by mechanism (blast-related or not) and setting (combat deployed or not). Participants with non-credible symptom reporting were excluded, leaving N = 1,685 of whom 81% had positive mTBI histories. Results: At a median 10 years since last mTBI, mTBI positive participants had higher HA prevalence (69% overall, 78% if 3 or more mTBIs) and greater HA burden (67% substantial/severe impact) than non-TBI controls (46% prevalence, 54% substantial/severe impact). In covariate-adjusted analysis, HA prevalence was higher with greater number of blast-related mTBIs (OR 1.81; 95% CI 1.48, 2.23), non-blast mTBIs while deployed (OR 1.42; 95% CI 1.14, 1.79), or non-blast mTBIs when not deployed (OR 1.23; 95% CI 1.02, 1.49). HA impact was only higher with blast-related mTBIs. Female identity, younger age, PTSD symptoms, and subjective sleep quality showed effects in both prevalence and impact models, with the largest mean HIT-6 elevation for PTSD symptoms. Additionally, combat deployment duration and depression symptoms were factors for HA prevalence, and Black race and Hispanic/Latino ethnicity were factors for HA impact. In sensitivity analyses, time since last mTBI and early HA onset were both non-significant. Conclusion: The prevalence of HA symptoms among formerly combat-deployed veterans and SMs is higher with more lifetime mTBIs regardless of how remote. Blast-related mTBI raises the risk the most and is uniquely associated with elevated HA burden. Other demographic and potentially modifiable risk factors were identified that may inform clinical care.

Harmonization of neuropsychological and other clinical endpoints: Pitfalls and possibilities.

This special issue brings together different methods for improving harmonization of existing (i.e., legacy) and future research data. We expect that when these methods are fully deployed, they will benefit research on various clinical conditions by allowing researchers to explore more nuanced questions using larger and more ethnically, socially, and economically diverse samples than previously available. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Role of Neuroimaging in Evolving TBI Research and Clinical Practice.

Neuroimaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) have been widely adopted in the clinical diagnosis and management of traumatic brain injury (TBI), particularly at the more acute and severe levels of injury. Additionally, a number of advanced applications of MRI have been employed in TBI-related clinical research with great promise, and researchers have used these techniques to better understand underlying mechanisms, progression of secondary injury and tissue perturbation over time, and relation of focal and diffuse injury to later outcome. However, the acquisition and analysis time, the cost of these and other imaging modalities, and the need for specialized expertise have represented historical barriers in extending these tools in clinical practice. While group studies are important in detecting patterns, heterogeneity among patient presentation and limited sample sizes from which to compare individual level data to well-developed normative data have also played a role in the limited translatability of imaging to wider clinical application. Fortunately, the field of TBI has benefitted from increased public and scientific awareness of the prevalence and impact of TBI, particularly in head injury related to recent military conflicts and sport-related concussion. This awareness parallels an increase in federal funding in the United States and other countries allocated to investigation in these areas. In this article we summarize funding and publication trends since the mainstream adoption of imaging in TBI to elucidate evolving trends and priorities in the application of different techniques and patient populations. We also review recent and ongoing efforts to advance the field through promoting reproducibility, data sharing, big data analytic methods, and team science. Finally, we discuss international collaborative efforts to combine and harmonize neuroimaging, cognitive, and clinical data, both prospectively and retrospectively. Each of these represent unique, but related, efforts that facilitate closing gaps between the use of advanced imaging solely as a research tool and the use of it in clinical diagnosis, prognosis, and treatment planning and monitoring.

Characterizing the Influence of Exposure to Military Sexual Trauma and Intimate Partner Violence on Mental Health Outcomes among Female Veterans.

Military sexual trauma (MST) has deleterious long-term psychological consequences. Among female U.S. military members, MST is associated with increased risk for future interpersonal victimization, such as experiencing intimate partner violence (IPV). Few studies have investigated the implications of the cumulative effects of IPV and MST on psychological functioning. This study examined rates of co-exposure to MST, IPV, and their cumulative impact on psychological symptoms. Data were collected from 308 female Veterans (FVets; age: M = 42, SD = 10.4) enrolled in an inpatient trauma-focused treatment program in a Veterans Administration (VA) hospital. Data were collected at program admission on symptoms of posttraumatic stress disorder (PTSD), depression, and current suicidal ideation. Lifetime trauma exposure was assessed using semi-structured interviews that identified adverse childhood events (ACEs) and combat theater deployment as well as MST and IPV. Group differences on psychological symptoms were examined among those exposed to MST, IPV, MST + IPV, and compared to FVets with ACEs or combat exposure, but no other adulthood interpersonal trauma (NAIT). Half of the sample (51%) reported experiencing both MST and IPV, approximately 29% reported MST, 10% reported IPV, and 10% reported NAIT. FVets in the MST + IPV group had worse PTSD and depression symptoms than either the MST or IPV groups. The NAIT group had the lowest scores on these measures. There were no group differences in current suicidal ideation; however, 53.5% reported at least one previous suicide attempt. FVets in this sample reported significant lifetime exposure to MST and IPV, with the majority having experienced MST + IPV. Exposure to MST + IPV was associated with greater PTSD and depression symptom severity, yet an overwhelming proportion reported current and past suicidal ideation regardless of trauma exposure history. These results demonstrate the importance of assessing for lifetime interpersonal trauma history when developing and providing mental and medical health interventions for FVets.

Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study.

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging >7 years post-radiotherapy. A healthy comparison group (n = 23) was also recruited. Participants completed age-appropriate measures of intellectual functioning, visual-motor integration, and motor coordination. Tractography was conducted using automated fiber quantification (AFQ). Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 12 tracts of interest. Overall, both white matter integrity (FA) and neuropsychological performance were lower in XRT patients while PRT patients were similar to healthy control participants with respect to both FA and cognitive functioning. These findings support improved long-term outcomes in PRT versus XRT. This exploratory study is the first to directly support for white matter integrity as a mechanism of cognitive sparing in PRT.

Assessing Pediatric Mild Traumatic Brain Injury and Its Recovery Using Resting-State Magnetoencephalography Source Magnitude Imaging and Machine Learning.

The objectives of this machine-learning (ML) resting-state magnetoencephalography (rs-MEG) study involving children with mild traumatic brain injury (mTBI) and orthopedic injury (OI) controls were to define a neural injury signature of mTBI and to delineate the pattern(s) of neural injury that determine behavioral recovery. Children ages 8-15 years with mTBI (n = 59) and OI (n = 39) from consecutive admissions to an emergency department were studied prospectively for parent-rated post-concussion symptoms (PCS) at: 1) baseline (average of 3 weeks post-injury) to measure pre-injury symptoms and also concurrent symptoms; and 2) at 3-months post-injury. rs-MEG was conducted at the baseline assessment. The ML algorithm predicted cases of mTBI versus OI with sensitivity of 95.5 ± 1.6% and specificity of 90.2 ± 2.7% at 3-weeks post-injury for the combined delta-gamma frequencies. The sensitivity and specificity were significantly better (p < 0.0001) for the combined delta-gamma frequencies compared with the delta-only and gamma-only frequencies. There were also spatial differences in rs-MEG activity between mTBI and OI groups in both delta and gamma bands in frontal and temporal lobe, as well as more widespread differences in the brain. The ML algorithm accounted for 84.5% of the variance in predicting recovery measured by PCS changes between 3 weeks and 3 months post-injury in the mTBI group, and this was significantly lower (p < 10-4) in the OI group (65.6%). Frontal lobe pole (higher) gamma activity was significantly (p < 0.001) associated with (worse) PCS recovery exclusively in the mTBI group. These findings demonstrate a neural injury signature of pediatric mTBI and patterns of mTBI-induced neural injury related to behavioral recovery.