Impact of repeated blast exposure on active-duty United States Special Operations Forces.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

Imaging Findings in Acute Traumatic Brain Injury: a National Institute of Neurological Disorders and Stroke Common Data Element-Based Pictorial Review and Analysis of Over 4000 Admission Brain Computed Tomography Scans from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.

In 2010, the National Institute of Neurological Disorders and Stroke (NINDS) created a set of common data elements (CDEs) to help standardize the assessment and reporting of imaging findings in traumatic brain injury (TBI). However, as opposed to other standardized radiology reporting systems, a visual overview and data to support the proposed standardized lexicon are lacking. We used over 4000 admission computed tomography (CT) scans of patients with TBI from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study to develop an extensive pictorial overview of the NINDS TBI CDEs, with visual examples and background information on individual pathoanatomical lesion types, up to the level of supplemental and emerging information (e.g., location and estimated volumes). We documented the frequency of lesion occurrence, aiming to quantify the relative importance of different CDEs for characterizing TBI, and performed a critical appraisal of our experience with the intent to inform updating of the CDEs. In addition, we investigated the co-occurrence and clustering of lesion types and the distribution of six CT classification systems. The median age of the 4087 patients in our dataset was 50 years (interquartile range, 29-66; range, 0-96), including 238 patients under 18 years old (5.8%). Traumatic subarachnoid hemorrhage (45.3%), skull fractures (37.4%), contusions (31.3%), and acute subdural hematoma (28.9%) were the most frequently occurring CT findings in acute TBI. The ranking of these lesions was the same in patients with mild TBI (baseline Glasgow Coma Scale [GCS] score 13-15) compared with those with moderate-severe TBI (baseline GCS score 3-12), but the frequency of occurrence was up to three times higher in moderate-severe TBI. In most TBI patients with CT abnormalities, there was co-occurrence and clustering of different lesion types, with significant differences between mild and moderate-severe TBI patients. More specifically, lesion patterns were more complex in moderate-severe TBI patients, with more co-existing lesions and more frequent signs of mass effect. These patients also had higher and more heterogeneous CT score distributions, associated with worse predicted outcomes. The critical appraisal of the NINDS CDEs was highly positive, but revealed that full assessment can be time consuming, that some CDEs had very low frequencies, and identified a few redundancies and ambiguity in some definitions. Whilst primarily developed for research, implementation of CDE templates for use in clinical practice is advocated, but this will require development of an abbreviated version. In conclusion, with this study, we provide an educational resource for clinicians and researchers to help assess, characterize, and report the vast and complex spectrum of imaging findings in patients with TBI. Our data provides a comprehensive overview of the contemporary landscape of TBI imaging pathology in Europe, and the findings can serve as empirical evidence for updating the current NINDS radiologic CDEs to version 3.0.

Comparison of brain imaging and physical health between research and clinical neuroimaging cohorts of ageing.

OBJECTIVES: To compare brain MRI measures between Adult Changes in Thought (ACT) participants who underwent research, clinical, or both MRI scans, and clinical health measures across the groups and non-MRI subjects. METHODS: Retrospective cohort study leveraging MRI, clinical, demographic, and medication data from ACT. Three neuroradiologists reviewed MRI scans using NIH Neuroimaging Common Data Elements (CDEs). Total brain and white matter hyperintensity (WMH) volumes, clinical characteristics, and outcome measures of brain and overall health were compared between groups. 1166 MRIs were included (77 research, 1043 clinical, and 46 both) and an additional 3146 participants with no MRI were compared. RESULTS: Compared to the group with research MRI only, the clinical MRI group had higher prevalence of the following: acute infarcts, chronic haematoma, subarachnoid haemorrhage, subdural haemorrhage, haemorrhagic transformation, and hydrocephalus (each P < .001). Quantitative WMH burden was significantly lower (P < .001) and total brain volume significantly higher (P < .001) in research MRI participants compared to other MRI groups. Prevalence of hypertension, self-reported cerebrovascular disease, congestive heart failure, dementia, and recent hospitalization (all P < .001) and diabetes (P = .002) differed significantly across groups, with smaller proportions in the research MRI group. CONCLUSION: In ageing populations, significant differences were observed in MRI metrics between research MRI and clinical MRI groups, and clinical health metric differences between research MRI, clinical MRI, and no-MRI groups. ADVANCES IN KNOWLEDGE: This questions whether research cohorts can adequately represent the greater ageing population undergoing imaging. These findings may also be useful to radiologists when interpreting neuroimaging of ageing.

Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology.

We present open-source tools for 3D analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (i) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (ii) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer's Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer's disease cases and controls. The tools are available in our widespread neuroimaging suite "FreeSurfer" ( https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools ).

Combat Deployed Service Members by Blast TBI and Service Separation Status 5-years Post-deployment: Comparison of Cognitive, Neurobehavioral, and Psychological Profiles of Those Who Left vs. Those Still Serving.

INTRODUCTION: Longitudinal research regarding the pre- and post-separation experience has been relatively limited, despite its potential as a major life transition. Separating from the military and re-integration to civilian life is noted to be a period of increased risk of significant adjustment challenges, which impacts a service member in a multitude of areas. Active duty service members with combat-related physical or mental health or pre-existing adjustment conditions may be more likely to separate from service and more at risk for post-military service adjustment problems. MATERIALS AND METHODS: This is a secondary data analysis from a prospective, observational, longitudinal, multicohort study involving deployed service members originally enrolled between 2008 and 2013 in combat or following medical evacuation to Landstuhl, Germany. Two combat-deployed cohorts were examined: non-head-injured control without blast exposure (n = 109) and combat-related concussion arising from blast (n = 165). Comprehensive clinical evaluations performed at 1 year and 5 year follow-up included identical assessment batteries for neurobehavioral, psychiatric, and cognitive outcomes. In addition to demographics collected at each study visit, the current analysis leveraged the Glasgow Outcome Scale Extended (GOS-E), a measure of overall global disability. For neurobehavioral impairment, the Neurobehavioral Rating Scale-Revised (NRS) was used as well as the Headache Impact Test (HIT-6) to assess headache burden. To compare psychiatric symptom burden between those separated to those still serving, the Clinician-Administered PTSD Scale for DSM-IV (CAPS) and Montgomery-Asberg Depression Rating Scale (MADRS) for depression were used as well as the Michigan Alcohol Screening Test (MAST) to be able to compare alcohol misuse across groups. Overall cognitive function/performance was defined for each service member by aggregating the 19 neuropsychological measures. RESULTS: Overall comparisons following adjustment by linear regression and correction for multiple comparisons by separation status subgroup for non-blast control or blast traumatic brain injury (TBI) identified significant differences at 5 years post-enrollment in measures of global disability, neurobehavioral impairment, and psychiatric symptom burden. Those who separated had worse global disability, worse neurobehavioral symptoms, worse Post-Traumatic Stress Disorder symptoms, and worse depression symptoms than active duty service members. While service members who sustain a mild blast TBI during combat are more likely to separate from service within 5 years, there is a proportion of those non-injured who also leave during this time frame. Clinical profiles of both groups suggest service members who separated have elevated psychiatric and neurobehavioral symptoms but not cognitive dysfunction. Interestingly, the symptom load in these same domains is lower for those without blast TBI who separated during this time frame. CONCLUSIONS: These results appear to support previous research depicting that, for some service members, transitioning out of the military and re-integrating into civilian life can be a challenging adjustment. Many factors, including personal and social circumstances, prior mental or emotional difficulties, availability of social or community support or resources, can influence the adjustment outcomes of veterans. Service members with prior adjustment difficulties and/or those with blast TBI history (and ongoing neurobehavioral symptoms) may find the transition from military to civilian life even more challenging, given the potential substantial changes in lifestyle, structure, identity, and support.

Intimate Partner Violence and Other Trauma Exposures in Females With Traumatic Brain Injury.

We examined whether females with a history of traumatic brain injury (TBI) and intimate partner violence (IPV) have greater exposure to lifetime trauma relative to females with TBI but no IPV history. Further, we assessed the effects of lifetime trauma on psychological outcomes after TBI. Female participants (n = 70; age M [standard deviation-SD] = 50.5 [15.2] years) with TBI (time since injury median [interquartile range -IQR] = 10.2 [5.3-17.8] years) completed a structured assessment of lifetime history of TBI, including an IPV module to query head injuries from physical violence by an intimate partner. We characterized lifetime trauma exposure with the Adverse Childhood Experiences (ACEs) questionnaire and Survey of Exposure to Community Violence (CV). We evaluated psychological functioning with self-report questionnaires of post-traumatic stress disorder (PTSD), depression, and anxiety symptoms. Compared with those with no IPV history (n = 51), participants reporting IPV-related head injuries (n = 19; 27.1%) reported more ACEs (M[SD] IPV: 4.5[2.9]; No IPV: 1.6[1.8], p < 0.001, d = 1.08) and greater CV (IPV: 17.5[8.4]; No IPV: 7.6[6.1], p < .0001, d = 1.26). Within the full sample, ACEs (ß = 0.21, 95% confidence interval [CI] = 0.04-0.39) and CV (ß = 0.07, 95% CI = 0.01-0.13) predicted worse PTSD symptoms, while IPV alone did not. Exposure to all three sources of trauma (ACEs, CV, and IPV) was associated with worse PTSD symptoms relative to fewer traumas. The results highlight the scope of traumatic exposures among TBI survivors and the importance of considering IPV and other lifetime trauma exposure in assessing and managing TBI. Trauma-informed interventions that are modified for TBI-related impairment may offer improved outcomes in managing psychological symptoms.

Optimizing Brain Health of United States Special Operations Forces.

United States Special Operations Forces (SOF) personnel are frequently exposed to explosive blasts in training and combat. However, the effects of repeated blast exposure on the human brain are incompletely understood. Moreover, there is currently no diagnostic test to detect repeated blast brain injury (rBBI). In this "Human Performance Optimization" article, we discuss how the development and implementation of a reliable diagnostic test for rBBI has the potential to promote SOF brain health, combat readiness, and quality of life.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org.

Chronic frontal neurobehavioural symptoms in combat-deployed military personnel with and without a history of blast-related mild traumatic brain injury.

OBJECTIVE: This study evaluated frontal behavioural symptoms, via the FrSBe self-report, in military personnel with and without a history of blast-related mild traumatic brain injury (mild TBI). METHODS: Prospective observational cohort study of combat-deployed service members leveraging 1-year and 5-year demographic and follow up clinical outcome data. RESULTS: The blast mild TBI group (n = 164) showed greater frontal behavioural symptoms, including clinically elevated apathy, disinhibition, and executive dysfunction, during a 5-year follow-up, compared to a group of combat-deployed controls (n = 107) without mild TBI history or history of blast exposure. We also explored changes inbehaviourall symptoms over a 4-year span, which showed clinically significant increases in disinhibition in the blast mild TBI group, whereas the control group did not show significant increases in symptoms over time. CONCLUSION: Our findings add to the growing evidence that a proportion of individuals who sustain mild TBI experience persistent behavioural symptoms. We also offer a demonstration of a novel use of the FrSBe as a tool for longitudinal symptom monitoring in a military mild TBI population.

The Effect of a Group Physical Activity Program on Behavior of Incarcerated Youth.

Behavioral health challenges are more prevalent in incarcerated youth than in the general youth population. Questions remain regarding whether physical activity programs can reduce behavioral health challenges in incarcerated youth. Data were available for 1,285 youths incarcerated between January 2017 and December 2018. The structured exercise program was implemented in January 2018. Primary outcomes were numbers of use of force (UoF) and of program modifications (PMs) indicative of delinquent behavior in pre- and post-exercise implementation periods. Rates per 1,000 person-days for UoF (10.0 in 2017 vs. 7.4 in 2018) and for PMs (36.7 vs. 22.9) were statistically different. For youths incarcerated both years, rates per 1,000 person-days for UoF (12.3 vs. 7.9), and for PMs (43.3 vs. 23.5) were statistically different. There was a reduction in behavior modifications in incarcerated youths after implementing the exercise program, but further studies are needed to confirm these results.

Integrating Neuroimaging Measures in Nursing Research.

BACKGROUND: Medical and scientific advancement worldwide has led to a longer lifespan. With the population aging comes the risk of developing cognitive decline. The incorporation of neuroimaging measures in evaluating cognitive changes is limited in nursing research. The aim of this review is to introduce nurse scientists to neuroimaging measures employed to assess the association between brain and cognitive changes. METHODS: Relevant literature was identified by searching CINAHL, Web of Science, and PubMed databases using the following keywords: "neuroimaging measures," "aging," "cognition," "qualitative scoring," "cognitive ability," "molecular," "structural," and "functional." RESULTS: Neuroimaging measures can be categorized into structural, functional, and molecular imaging approaches. The structural imaging technique visualizes the anatomical regions of the brain. Visual examination and volumetric segmentation of select structural sequences extract information such as white matter hyperintensities and cerebral atrophy. Functional imaging techniques evaluate brain regions and underlying processes using blood-oxygen-dependent signals. Molecular imaging technique is the real-time visualization of biological processes at the cellular and molecular levels in a given region. Examples of biological measures associated with neurodegeneration include decreased glutamine level, elevated total choline, and elevated Myo-inositol. DISCUSSION: Nursing is at the forefront of addressing upstream factors impacting health outcomes across a lifespan of a population at increased risk of progressive cognitive decline. Nurse researchers can become more facile in using these measures both in qualitative and quantitative methodology by leveraging previously gathered neuroimaging clinical data for research purposes to better characterize the associations between symptom progression, disease risk, and health outcomes.

Protocol for the Systematic Fixation, Circuit-Based Sampling, and Qualitative and Quantitative Neuropathological Analysis of Human Brain Tissue.

Human brain tissue has long been a critical resource for neuroanatomy and neuropathology, but with the advent of advanced imaging and molecular sequencing techniques, it has become possible to use human brain tissue to study, in great detail, the structural, molecular, and even functional underpinnings of human brain disease. In the century following the first description of Alzheimer's disease (AD), numerous technological advances applied to human tissue have enabled novel diagnostic approaches using diverse physical and molecular biomarkers, and many drug therapies have been tested in clinical trials (Schachter and Davis, Dialogues Clin Neurosci 2:91-100, 2000). The methods for brain procurement and tissue stabilization have remained somewhat consistently focused on formalin fixation and freezing. Although these methods have enabled research protocols of multiple modalities, new, more advanced technologies demand improved methodologies for the procurement, characterization, stabilization, and preparation of both normal and diseased human brain tissues. Here, we describe our current protocols for the procurement and characterization of fixed brain tissue, to enable systematic and precisely targeted diagnoses, and describe the novel, quantitative molecular, and neuroanatomical studies that broadly expand the use of formalin-fixed, paraffin-embedded (FFPE) tissue that will further our understanding of the mechanisms underlying human neuropathologies.

A Comparative Analysis of Depressive Symptoms Following Sports-Related Concussion in Youth Athletes Versus Their Age-Matched Non-concussed Counterparts.

Background and objective Athletics is the leading cause of pediatric concussion, and depression is a major comorbidity associated with concussion in the pediatric population. Prior studies have described the risk of depression after concussion in high school-, collegiate-, and elite-level athletes, but there is scarce data on younger athletes. Interpretation of existing research on the association of depression with concussions in youth athletes is complicated by diverse study designs, varying measures of depression, differing timelines for symptom development, and a lack of control groups. Furthermore, limited research exists on sex-related differences in the development of depressive symptoms following sports-related concussions (SRC) in younger athletes. This study used the Seattle Pediatric Concussion Research Collaborative (SPCRC) Data Repository to compare depressive symptoms between youth athletes at one month post-SRC and non-concussed age-matched controls by using a standardized measure of depressive symptoms: the Patient Health Questionnaire-9 (PHQ-9). The secondary goal was to compare PHQ-9 scores between males and females for both concussed and non-concussed groups. Methods This study entailed a secondary analysis of data collected as part of the SPCRC Data Repository. We conducted a retrospective subgroup analysis of PHQ-9 scores at one month post-concussion for concussed youth athletes. We compared the PHQ9 scores of concussed youth athletes with PHQ-9 scores collected at the time of enrollment for non-concussed youth athletes. Results After random age-matching, a cohort of 266 patients (133 in the concussed group and 133 in the non-concussed control group) was included in the final analysis. The mean age was 13.8 years (range: 5-18 years). For the concussed group, a history of SRC was associated with a higher mean total PHQ-9 score at one month post-concussion compared with the control group at the time of enrollment (6.14 ±5.46 versus 1.53 ±1.81, respectively, p<0.0001). All nine subdomains of the PHQ-9 showed significantly higher scores in the concussion group compared with the control group (p<0.0001). Significantly higher scores were observed when comparing mean total PHQ-9 scores for male athletes in the concussion group with male athletes in the control group (7.03 ±5.72 versus 1.59 ±1.66, p<0.0001) and for female athletes in the concussion group compared with female controls (5.28 ±5.10 versus 1.49 ±1.92, p<0.0001). No significant differences were observed between sexes for total PHQ-9 scores or PHQ-9 subscores. Conclusion At one month post concussion, youth with SRC demonstrated higher levels of depressive symptoms as measured by PHQ-9 compared with age-matched typically developing controls. No significant differences were identified in total PHQ-9 scores and subscores between male and female participants for either the concussion or control group. This study suggests that clinicians need to be vigilant and monitor for symptoms of depression in young athletes for at least one month post-concussion.

Emotional Resilience Predicts Preserved White Matter Microstructure Following Mild Traumatic Brain Injury.

BACKGROUND: Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype. METHODS: The present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion magnetic resonance images from 172 patients with mTBI were analyzed to compute individual diffusion tensor imaging maps at 2 weeks and 6 months after injury. RESULTS: By comparing the diffusion tensor imaging parameters between the two phenotypes at global, regional, and voxel levels, emotionally resilient patients were shown to have higher axial diffusivity compared with neuropsychiatrically distressed patients early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in neuropsychiatrically distressed patients, with greater decrease of global axial diffusivity and more widespread decrease of regional axial diffusivity during the first 6 months after injury compared with emotionally resilient patients. CONCLUSIONS: These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest that diffusion magnetic resonance imaging can provide short- and long-term imaging biomarkers of resilience.

Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury.

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77-0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98-1.25 per log unit increase) levels. Elevated day-of-injury plasma GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.

Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study.

Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE <8 vs = 8) even after accounting for demographic, clinical, and other imaging factors. DTI provides reliable imaging biomarkers of dynamic WM microstructural changes after mTBI that have utility for patient selection and treatment response in clinical trials. Continued technological advances in the sensitivity, specificity, and precision of diffusion magnetic resonance imaging hold promise for routine clinical application in mTBI.

Long-Term Effects of Repeated Blast Exposure in United States Special Operations Forces Personnel: A Pilot Study Protocol.

Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.

Acute Postoperative Seizures and Engel Class Outcome at 1 Year Postselective Laser Amygdalohippocampal Ablation for Mesial Temporal Lobe Epilepsy.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) for mesial temporal lobe epilepsy is a safe, minimally invasive alternative to traditional surgical approaches. Prognostic factors associated with efficacy are debated; preoperative epilepsy duration and semiology seem to be important variables. OBJECTIVE: To determine whether acute postoperative seizure (APOS) after MRgLITT for mesial temporal lobe epilepsy is associated with seizure freedom/Engel class outcome at 1 year. METHODS: A single-institution retrospective study including adults undergoing first time MRgLITT for mesial temporal lobe epilepsy (2010-2019) with ≥1-year follow-up. Preoperative data included sex, epilepsy duration, number of antiepileptics attempted, weekly seizure frequency, seizure semiology, and radiographically verified anatomic lesion at seizure focus. Postoperative data included clinical detection of APOS within 7 days postoperatively, and immediate amygdala, hippocampal, entorhinal, and parahippocampal residual volumes determined using quantitative imaging postprocessing. Primary outcome was seizure freedom/Engel classification 1 year postoperatively. RESULTS: Of 116 patients, 53% (n = 61) were female, with an average epilepsy duration of 21 (±14) years, average 6 failed antiepileptics (±3), and weekly seizure frequency of 5. APOS was associated with worse Engel class ( P = .010), conferring 6.3 times greater odds of having no improvement vs achieving seizure freedom at 1 year. Residual amygdala, hippocampal, entorhinal, and parahippocampal volumes were not statistically significant prognostic factors. CONCLUSION: APOS was associated with a lower chance of seizure freedom at 1 year post-MRgLITT for mesial temporal lobe epilepsy. Amygdala, hippocampal, entorhinal, and parahippocampal residual volumes after ablation were not significant prognostic factors.

Global Disability Trajectories Over the First Decade Following Combat Concussion.

OBJECTIVE: To examine global disability trajectories in US military with and without traumatic brain injury (TBI) over the first decade following deployment to identify risk profiles for better intervention stratification, hopefully reducing long-term cost. SETTING: Patients and participants were enrolled in combat or directly following medical evacuation at the time of injury and followed up every 6 months for 10 years. PARTICIPANTS: There are 4 main groups (n = 475), 2 primary and 2 exploratory: (1) combat-deployed controls without a history of blast exposure "non-blast- control" (n = 143), (2) concussive blast TBI "'blast-TBI" (n = 236) (primary), (3) combat-deployed controls with a history of blast exposure "blast-control" (n = 54), and (4) patients sustaining a combat concussion not from blast "non-blast-TBI" (n = 42) (exploratory). DESIGN: Prospective, observational, longitudinal study. MAIN MEASURES: Combat concussion, blast exposure, and subsequent head injury exposure over the first decade post-deployment. Global disability measured by the Glasgow Outcome Scale Extended (GOSE). RESULTS: Latent class growth analysis identified 4 main trajectories of global outcome, with service members sustaining combat concussion 37 to 49 times more likely to be in the worse disability trajectories than non-blast-controls (blast-TBI: odds ratio [OR] = 49.33; CI, 19.77-123.11; P < .001; non-blast-TBI: OR = 37.50; CI, 10.01-140.50; P < .001). Even blast-exposed-controls were 5 times more likely to be in these worse disability categories compared with non-blast-controls (OR = 5.00; CI, 1.59-15.99; P = .007). Adjustment for demographic factors and subsequent head injury exposure did not substantially alter these odds ratios. CONCLUSIONS: Very high odds of poor long-term outcome trajectory were identified for those who sustained a concussion in combat, were younger at the time of injury, had lower education, and enlisted in the Army above the risk of deployment alone. These findings help identify a risk profile that could be used to target early intervention and screen for poor long-term outcome to aid in reducing the high public health cost and enhance the long-term quality of life for these service members following deployment.