Faculty Bibliography

BACKGROUND:Public awareness of concussion has grown significantly over the past 2 decades, driven largely by media coverage of sports-related injuries. This has paralleled a rise in traumatic brain injury (TBI)-related emergency department visits, underscoring the need for specialized concussion care centers. Despite this, most existing programs focus on sports or pediatric populations, leaving critical care gaps. RECENT FINDINGS/RESULTS:The NYU Langone Concussion Center was established in 2013 to address these gaps by providing interdisciplinary care for both sports-related and non-sports-related concussions. Approximately 60% of cases seen at the center are not sports related. This article outlines the center's inception, operational model, patient demographics, and evolution over the past decade. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:Lessons learned from the NYU Langone model offer valuable guidance for developing comprehensive concussion programs that can serve diverse urban populations. Key strategies include cross-specialty collaboration, flexible infrastructure, and systems-level integration to address heterogeneous mechanisms of injury and outcomes.

INTRODUCTION/BACKGROUND:Repetitive head impacts (RHIs) have been linked to later life neurodegeneration, yet the in vivo structural correlates of cumulative biomechanical loading remain unclear. We examined whether regional ventricular morphology in former American football players reflects exposure burden and traumatic encephalopathy syndrome (TES) classification. METHODS:Participants included 170 male former football players and 54 age-matched asymptomatic male controls from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Subject-specific manual segmentation quantified lateral ventricle, inferior horn, third ventricle, and fourth ventricle volumes. Group and exposure associations were tested using generalized least squares models. RESULTS:Former players showed larger left inferior lateral ventricle volume than controls, with the largest effects among professional players. Greater cumulative linear and rotational acceleration exposure was associated with enlargement across lateral ventricular and inferior horn regions. DISCUSSION/CONCLUSIONS:Regional ventricular enlargement may represent an in vivo marker of cumulative biomechanical loading after RHI exposure.

INTRODUCTION/BACKGROUND:Chronic traumatic encephalopathy (CTE) is a tauopathy linked to repetitive head impacts. Factors influencing brain regional susceptibility to tau deposition and spreading remain unclear. METHODS:We used three datasets: [18F]flortaucipir positron emission tomography (PET) in 157 former professional American football players and 53 controls (DIAGNOSE CTE); cortical myelin water fractions (MWF) in 50 healthy individuals (Myelin Water Atlas); and white matter (WM) tract MWF and functional connectivity (FC) in 100 healthy individuals (Human Connectome Project). We tested associations between tau-PET uptake and covariance in football players and typical cortical gray matter (GM) MWF, WM tract MWF, and FC. RESULTS:Cortical regions with lower typical GM MWF showed higher tau-PET uptake (β = -0.399, p = 0.001). WM tracts with lower typical MWF were associated with higher tau-PET covariance (β = -0.238, p < 0.001). Higher typical FC was associated with higher tau-PET covariance (β = 0.447, p < 0.001). DISCUSSION/CONCLUSIONS:In former football players at risk for CTE, regional susceptibility to tau deposition may be driven by low myelin and high FC.

Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45-74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45-74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen's d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen's d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

Most traumatic brain injuries (TBIs) are classified as mild (mTBI), yet they can still be associated with lasting behavioral, sensory, cognitive, and neural changes. Recent studies show that individuals with a history of mTBI (hmTBI) experience auditory sensitivities (e.g., noise annoyance and hyperacusis). Here, we tested whether we could detect early auditory processing alterations in individuals with a hmTBI using well-characterized event-related potentials (ERPs) sensitive to auditory sensory responses, specifically the N100, mismatch negativity (MMN), and the deviance-related negativity (DRN) waveform. Seventeen participants with a self-reported hmTBI and 25 control participants completed a passive oddball task in which infrequent pitch-deviant tones were interleaved amidst frequent standard tones, during which EEG was recorded. We examined N100, MMN, and DRN amplitude and N100 and MMN latency, using frequentist and Bayesian analyses. Across analyses, there were no significant group differences. The Bayes factors provided anecdotal to moderate support for the null hypothesis. These results suggest that undergraduates with hmTBI may be more likely to exhibit preserved early auditory processing. Future research should examine whether later, top-down processes contribute to enduring auditory symptoms.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). In CTE, hyperphosphorylated tau (p-tau) aggregates are found in neurons at the depth of cortical sulci close to the gray matter/white matter (GM/WM) boundary. To date, CTE can only be diagnosed postmortem by neuropathological examination. Traumatic encephalopathy syndrome (TES) is the clinical syndrome purported to be associated with CTE pathology. The aim of this study is to investigate microstructural properties at the GM/WM boundary in individuals with a history of exposure to RHI and clinical features of CTE (i.e., TES). Diffusion magnetic resonance imaging (dMRI), TES diagnoses, and cerebrospinal fluid (CSF) biomarkers were acquired from 165 male former American football players (age: 57.29 ± 8.23 years) from the DIAGNOSE CTE Research Project, a multicenter, observational cohort study. Fractional anisotropy (FA) was measured at the GM/WM boundary of the whole brain. In addition, a widely used method (tract-based spatial statistics [TBSS]) was applied to measure FA of central WM. We used analyses of covariance to test associations between FA and TES. Furthermore, we used linear regressions to test associations between FA and nine CSF biomarkers (i.e., p-tau-181, -217, -231, total tau, amyloid β [Aβ]_1-40, Aβ_1-42, glial fibrillary acidic protein [GFAP], neurofilament light [NfL], and soluble triggering receptor expressed on myeloid cells-2 [sTREM2]). We report an association between higher FA at the GM/WM boundary and higher levels of certainty for CTE pathology (F(1, 147) = 5.781, 95% confidence interval (CI) = 0.0003-0.003, p = 0.035) as well as neurobehavioral dysregulation (F(1, 148) = 7.559, 95% CI = 0.001-0.009, p = 0.020), and functional dependence/dementia (F(1, 148) = 5.046, 95% CI = 0.0004-0.006, p = 0.039). In addition, we report an association between higher FA at the GM/WM boundary and higher CSF p-tau-181 (β = 0.272, 95% CI = 0.078-0.466, p = 0.029) and p-tau-217 (β = 0.295, 95% CI = 0.102-0.488, p = 0.027). FA of the central WM was not associated with TES diagnoses. Taken together, these findings suggest that dMRI at the GM/WM boundary could be used to investigate microstructural alterations suggestive of tau pathology-associated neurodegeneration in individuals with TES, the clinical presentation of CTE. Future studies are needed to validate this approach and to identify clinically useful cutoff values for dMRI metrics.

Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions-amygdala, hippocampus and thalamus-which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein

Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45-74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45-74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

The cavum septum pellucidum (CSP) is a small cerebrospinal fluid-filled space found between the lateral ventricles of the forebrain that is often used as a biomarker for neurological disease and brain injury. The incidence of the CSP varies widely in different studies, with many reports finding that the CSP is frequently absent in healthy brains. Variables such as race, age and sex are typically not well-reported in CSP studies, presenting a challenge to understanding the normal distribution of the CSP in adult human brains. Moreover, the small size and frequently indistinct borders present a challenge for automated segmentation of the CSP. To address these issues, we developed a novel manual parcelation approach to volumetrically segment the CSP in high-resolution T1-weighted structural MRIs from male and female participants in the young adult dataset of the Human Connectome Project (HCP). We identified the CSP in 95.6% of subjects, compared to 57.1% when the automated segmentation approach was used on the same subjects. The CSP volume was significantly larger in male than female brains, both in terms of raw volume and volumes normalized for intracranial volume. To our knowledge, this study is the first to develop and validate a segmentation protocol for CSP volume, and to evaluate both the incidence and volume of the CSP in a representative population of young adults. Overall, these results provide a more accurate representation of the CSP in control populations, laying an improved foundation for its potential use as a biomarker for various disorders.