Differences in Brain Volume in Military Service Members and Veterans After Blast-Related Mild TBI: A LIMBIC-CENC Study.

Importance: Blast-related mild traumatic brain injuries (TBIs), the "signature injury" of post-9/11 conflicts, are associated with clinically relevant, long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear.

Objective: To investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members.

Design, Setting, And Participants: Prospective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in this analysis between 2014 and 2023.

Direct segmentation of cortical cytoarchitectonic domains using ultra-high-resolution whole-brain diffusion MRI.

We assess the potential of detecting cortical laminar patterns and areal borders by directly clustering voxel values of microstructural parameters derived from high-resolution mean apparent propagator (MAP) magnetic resonance imaging (MRI), as an alternative to conventional template-warping-based cortical parcellation methods. We acquired MAP-MRI data with 200m resolution in a fixed macaque monkey brain. To improve the sensitivity to cortical layers, we processed the data with a local anisotropic Gaussian filter determined voxel-wise by the plane tangent to the cortical surface.

Long-term retention of real-world experiences in a patient with profound amnesia.

The medial temporal lobe (MTL) is known to be critical for healthy memory function, but patients with MTL damage can, under certain circumstances, demonstrate successful learning of novel information encountered outside the laboratory. Here, we describe a patient, D.C.

Internet-Guided Cognitive Behavioral Therapy for Insomnia Among Patients With Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Many military service members and veterans report insomnia after sustaining traumatic brain injury (TBI). Limitations of first-line treatment, cognitive-behavioral therapy for insomnia (CBT-I), include availability of qualified clinicians, low completion rates, and cost.

Objective: To investigate the feasibility and efficacy of internet-guided CBT-I (eCBT-I) in military service members and veterans with insomnia and a history of TBI.

Programmatic Assessment of Clinical Reasoning: New Opportunities to Meet an Ongoing Challenge.

 Clinical reasoning is essential to physicians' competence, yet assessment of clinical reasoning remains a significant challenge. Clinical reasoning is a complex, evolving, non-linear, context-driven, and content-specific construct which arguably cannot be assessed at one point in time or with a single method. This has posed challenges for educators for many decades, despite significant development of individual assessment methods.

A Pilot Study Investigating the Use of Serum Glial Fibrillary Acidic Protein to Monitor Changes in Brain White Matter Integrity After Repetitive Head Hits During a Single Collegiate Football Game.

Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes.

Effect of Human Head Shape on the Risk of Traumatic Brain Injury: A Gaussian Process Regression-Based Machine Learning Approach.

Introduction: Computational head injury models are promising tools for understanding and predicting traumatic brain injuries. However, most available head injury models are "average" models that employ a single set of head geometry (e.g.

Evaluating the Acceptability and Feasibility of Collecting Passive Smartphone Data to Estimate Psychological Functioning in U.S. Service Members and Veterans: A Pilot Study.

Introduction: This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the acceptability of digital phenotyping by (1a) quantifying the proportion of participants willing to download the app and rates of dropout and app discontinuation and (1b) reviewing the stated reasons for both refusing and discontinuing use of the app. The second aim was to investigate technical feasibility by (2a) characterizing the amount and frequency of transferred data and (2b) documenting technical challenges.

Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.

Background And Objectives: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories.

Methods: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms.

Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group.

Design, Setting, And Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022.

Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms.

Purpose: We report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or fractured, to create a "powder-averaged" emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues.

Methods: Two-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries.

"Pscore": A Novel Percentile-Based Metric to Accurately Assess Individual Deviations in Non-Gaussian Distributions of Quantitative MRI Metrics.

Background: Quantitative magnetic resonance imaging (MRI) metrics could be used in personalized medicine to assess individuals against normative distributions. Conventional Zscore analysis is inadequate in the presence of non-Gaussian distributions. Therefore, if quantitative MRI metrics deviate from normality, an alternative is needed.

'Pscore' - A Novel Percentile-Based Metric to Accurately Assess Individual Deviations in Non-Gaussian Distributions of Quantitative MRI Metrics.

Background: Quantitative MRI metrics could be used in personalized medicine to assess individuals against normative distributions. Conventional Zscore analysis is inadequate in the presence of non-Gaussian distributions. Therefore, if quantitative MRI metrics deviate from normality, an alternative is needed.

Associations between white matter integrity and postural control in adults with traumatic brain injury.

Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration.

A Narrative Review of Existing and Developing Biomarkers in Acute Traumatic Brain Injury for Potential Military Deployed Use.

Introduction: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in both adult civilian and military populations. Currently, diagnostic and prognostic methods are limited to imaging and clinical findings. Biomarker measurements offer a potential method to assess head injuries and help predict outcomes, which has a potential benefit to the military, particularly in the deployed setting where imaging modalities are limited.

Correspondence of mean apparent propagator MRI metrics with phosphorylated tau and astrogliosis in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy is a neurodegenerative disease that is diagnosed and staged based on the localization and extent of phosphorylated tau pathology. Although its identification remains the primary diagnostic criteria to distinguish chronic traumatic encephalopathy from other tauopathies, the hyperphosphorylated tau that accumulates in neurofibrillary tangles in cortical grey matter and perivascular regions is often accompanied by concomitant pathology such as astrogliosis. Mean apparent propagator MRI is a clinically feasible diffusion MRI method that is suitable to characterize microstructure of complex biological media efficiently and comprehensively.

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).

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts.

Objective: The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes.

Methods: This pilot study comprised two independent cohorts. The first cohort-part of a Traumatic Head Injury Neuroimaging Classification (THINC) study-with a mean age of 46 years was composed of uninjured controls (UIC, = 30) and mTBI patients ( = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings.

High Lifetime Blast Exposure Using the Blast Exposure Threshold Survey Is Associated With Worse Warfighter Brain Health Following Mild Traumatic Brain Injury.

The purpose of this study was to extend previous research by examining the relationship between lifetime blast exposure and neurobehavioral functioning after mild TBI (MTBI) by (a) using a comprehensive measure of lifetime blast exposure, and (b) controlling for the influence of post-traumatic stress disorder (PTSD). Participants were 103 United States service members and veterans (SMVs) with a medically documented diagnosis of MTBI, recruited from three military treatment facilities (74.8%) and community-based recruitment initiatives (25.

Multimodal anatomical mapping of subcortical regions in marmoset monkeys using high-resolution MRI and matched histology with multiple stains.

Subcortical nuclei and other deep brain structures play essential roles in regulating the central and peripheral nervous systems. However, many of these nuclei and their subregions are challenging to identify and delineate in conventional MRI due to their small size, hidden location, and often subtle contrasts compared to neighboring regions. To address these limitations, we scanned the whole brain of the marmoset monkeys in ex vivo using a clinically feasible diffusion MRI method, called the mean apparent propagator (MAP)-MRI, along with T2W and MTR (T1-like contrast) images acquired at 7 Tesla.

Enhanced in vivo blood brain barrier transcytosis of macromolecular cargo using an engineered pH-sensitive mouse transferrin receptor binding nanobody.

Background: The blood brain barrier limits entry of macromolecular diagnostic and therapeutic cargos. Blood brain barrier transcytosis via receptor mediated transport systems, such as the transferrin receptor, can be used to carry macromolecular cargos with variable efficiency. Transcytosis involves trafficking through acidified intracellular vesicles, but it is not known whether pH-dependent unbinding of transport shuttles can be used to improve blood brain barrier transport efficiency.

Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury.

Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts ( = 93), and one replication cohort ( = 180).

Enhanced Blood Brain Barrier Transcytosis of Macromolecular Cargo Using an Engineered pH-sensitive Mouse Transferrin Receptor Binding Nanobody.

Background: The blood brain barrier limits entry of macromolecular diagnostic and therapeutic cargos. Blood brain barrier transcytosis via receptor mediated transport systems, such as the transferrin receptor, can be used to carry macromolecular cargos with variable efficiency. Transcytosis involves trafficking through acidified intracellular vesicles, but it is not known whether pH-dependent unbinding of transport shuttles can be used to improve blood brain barrier transport efficiency.