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Objective: We examined whether brain hemodynamic responses, gait, and cognitive performances under single- and dual-task conditions predict falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) with relapsing-remitting and progressive subtypes., Methods: Participants with relapsing-remitting ( n = 53, mean age = 65.02 ± 4.17 years, %female = 75.5) and progressive ( n = 28, mean age = 64.64 ± 4.31 years, %female = 50) multiple sclerosis (MS) subtypes completed a dual-task-walking paradigm and reported falls during longitudinal follow-up using a monthly structured telephone interview. We used functional near-infrared spectroscopy (fNIRS) to assess oxygenated hemoglobin (HbO) in the prefrontal cortex during active walking and while performing a cognitive test under single- and dual-task conditions., Results: Adjusted general estimating equations models indicated that higher HbO under dual-task walking was significantly associated with a reduction in the odds of reporting falls among participants with relapsing-remitting (odds ratio (OR) = 0.472, p = 0.004, 95% confidence interval (CI) = 0.284-0.785), but not progressive (OR = 1.056, p = 0.792, 95% CI = 0.703-1.588) MS. In contrast, faster stride velocity under dual-task walking was significantly associated with a reduction in the odds of reporting falls among progressive (OR = 0.658, p = 0.004, 95% CI = 0.495-0.874), but not relapsing-remitting (OR = 0.998, p = 0.995, 95% CI = 0.523-1.905) MS., Conclusion: Findings suggest that higher prefrontal cortex activation levels during dual-task walking, which may represent compensatory reallocation of brain resources, provide protection against falls for OAMS with relapsing-remitting subtype., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.I. has a minor share in fNIRS device. All other authors have no conflicts of interest to report in relation to the current article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65-97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18-63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mobility and cognitive impairment are prevalent and co-occurring in older adults with multiple sclerosis (OAMS), yet there is limited research concerning the role of disability status in the cognitive control of gait among OAMS., Objective: We investigated the levels of prefrontal cortex (PFC) activation, using oxygenated hemoglobin (HbO 2 ), during cognitively-demanding tasks in OAMS with lower and higher disability using functional near-infrared spectroscopy (fNIRS) to: (1) identify PFC activation differences in single task walk and cognitively-demanding tasks in OAMS with different levels of disability; and (2) evaluate if disability may moderate practice-related changes in neural efficiency in OAMS., Methods: We gathered data from OAMS with lower (n = 51, age = 65 ± 4 years) or higher disability (n = 48, age = 65 ± 5 years), using a cutoff of 3 or more, in the Patient Determined Disease Steps, for higher disability, under 3 different conditions (single-task walk, Single-Task-Alpha, and Dual-Task-Walk [DTW]) administered over 3 counterbalanced, repeated trials., Results: OAMS who had a lower disability level exhibited decreased PFC activation levels during Single-Task-Walk (STW) and larger increases in PFC activation levels, when going from STW to a cognitively-demanding task, such as a DTW, than those with higher disability. OAMS with a lower disability level exhibited greater declines in PFC activation levels with additional within session practice than those with a higher disability level., Conclusions: These findings suggest that disability moderates brain adaptability to cognitively-demanding tasks and demonstrate the potential for fNIRS-derived outcome measures to complement neurorehabilitation outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Izzetoglu has a minor share in fNIRS device. All other authors have no conflicts of interest to report in relation to the current article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Rationale and Objectives: This study examined the brain effects of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which are incompletely understood. Our objective was to ascertain within-person changes associated with mild coronavirus disease 2019 (COVID-19) in otherwise healthy adults., Materials and Methods: We leveraged existing pre-pandemic baseline neuroimaging and neurocognitive data, and collected follow-up data from uninfected controls and individuals with prior mild COVID-19, during December 2020 and January 2021, when vaccines were not yet available. We compared change during follow-up in patients (n = 5) versus controls (n = 15)., Results: We identified a decrease of intracellular volume fraction (ICVF), decrease of isotropic volume fraction (ISO) and decrease of orientation dispersion index (ODI) in multiple inferior frontal regions of interest in COVID-19 patients; this longitudinal change was significantly different from the control group which demonstrated increases in equivalent measures. This pattern suggests injury with neuronal loss and/or inflammation as underlying mechanisms. Neurocognitive studies identified a pattern of cognitive decline (processing speed, executive function, verbal learning, working memory) in patients, that did not reach significance., Conclusion: Our pilot data suggests that mild COVID-19 may result in brain pathology and impact neurocognitive function in younger adults in a manner parallel to prior findings in older individuals. Though findings may not generalize to other SARS-CoV-2 variants, larger longitudinal studies of mild COVID-19 should be undertaken to understand the potential clinical implications of these findings over the longer term., Competing Interests: The authors declare that they have no known completing financial interest of personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background/objective: Falls research in older adults with MS (OAMS) is scarce, and no studies have reported on the association between life-space mobility and falls in this group. Herein, we hypothesized that higher baseline life-space scores would be associated with reduced odds of reporting falls during follow-up, and explored whether the association differed by MS subtype (progressive vs. relapsing-remitting)., Methods: OAMS (n = 91, mean age = 64.7 ± 4.3ys, %female = 66.9,%progressive MS = 30.7) completed the University of Alabama at Birmingham Life-Space-Assessment (UAB-LSA) scale and reported falls during a structured monthly telephone interview during follow-up (mean = 16.39 ± 11.44 months). General Estimated Equations (GEE) models were utilized to determine whether UAB-LSA scores predicted falls during follow-up., Results: GEE models revealed that higher UAB-LSA scores were associated with a significant reduction in the odds of falling during follow-up (OR = 0.69, p = 0.012, 95 %CI = 0.51 to 0.92). Stratified analyses revealed that this association was significant in progressive (OR = 0.57, p = 0.004, 95 %CI = 0.39 to 0.84), but not relapsing-remitting (OR = 0.93, p = 0.779, 95 %CI = 0.57 to 1.53) MS., Conclusion: Higher life-space mobility was associated with lower odds of falling among OAMS with progressive subtype. The UAB-LSA may complement existing mobility measures for predicting fall risk., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction persisting 30 days or more following mild traumatic brain injury (mTBI)., Summary of Review: A search of PubMed and Embase from inception through June 2022 identified 42 studies that associated genetic variants with the presence of symptoms or cognitive dysfunction 30 days or more following mTBI. Risk of bias was assessed for each publication using the Newcastle Ottawa Scale (NOS). Fifteen of the 22 studies evaluating apolipoprotein E ( APOE ) ɛ4 concluded that it was associated with worse outcomes and 4 of the 8 studies investigating the brain-derived neurotrophic factor ( BDNF ) reported the Val66Met allele was associated with poorer outcomes. The review also identified 12 studies associating 28 additional variants with mTBI outcomes. Of these, 8 references associated specific variants with poorer outcomes. Aside from analyses comparing carriers and noncarriers of APOE ɛ4 and BDNF Val66Met, most of the reviewed studies were too dissimilar, particularly in terms of specific outcome measures but also in genes examined, to allow for direct comparisons of their findings. Moreover, these investigations were observational and subject to varying degrees of bias., Conclusions: The most consistent finding across articles was that APOE ɛ4 is associated with persistent post-mTBI impairment (symptoms or cognitive dysfunction) more than 30 days after mTBI. The sparsity of other well-established and consistent findings in the mTBI literature should motivate larger, prospective studies, which characterize the risk for persistent impairment with standardized outcomes in mTBI posed by other genetic variants influencing mTBI recovery., Competing Interests: Michael L. Lipton receives funding from the National Institutes of Health. The remaining authors have no conflicts of interest or funding to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Soccer heading is adversely associated with neurocognitive performance, but whether greater neck strength or anthropometrics mitigates these outcomes is controversial. Here, we examine the effect of neck strength or anthropometrics on associations of soccer heading with neurocognitive outcomes in a large cohort of adult amateur players., Methods: 380 adult amateur league soccer players underwent standardized measurement of neck strength (forward flexion, extension, left lateral flexion, right lateral flexion) and head/neck anthropometric measures (head circumference, neck length, neck circumference and neck volume). Participants were assessed for heading (HeadCount) and cognitive performance (Cogstate) on up to 7 visits over a period of two years. Principal components analysis (PCA) was performed on 8 neck strength and anthropometric measures. We used generalized estimating equations to test the moderation effect of each of the three PCs on 8 previously identified adverse associations of 2-week and 12-month heading estimates with cognitive performance (psychomotor speed, immediate verbal recall, verbal episodic memory, attention, working memory) and of unintentional head impacts on moderate to severe central nervous system symptoms., Results: 3 principal components (PC's) account for 80% of the variance in the PCA. In men, PC1 represents head/neck anthropometric measures, PC2 represents neck strength measures, and PC3 represents the flexor/extensor (F/E) ratio. In women, PC1 represents neck strength, PC2 represents anthropometrics, and PC3 represents the F/E ratio. Of the 48 moderation effects tested, only one showed statistical significance after Bonferroni correction, which was not robust to extensive sensitivity analyses., Conclusion: Neither neck strength nor anthropometrics mitigate adverse associations of soccer heading with cognitive performance in adult amateur players., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Older adults with multiple sclerosis (OAMS) have declines in walking and physical performance that may erode community mobility defined as the spatial extent of mobility in one's daily life and environment., Objective: This study provided the first application and validation of the University of Alabama Birmingham Study of Aging Life-Space Assessment (UAB LSA) as a measure of community mobility in OAMS., Methods: The sample included 97 OAMS and 108 healthy controls (HCs) who completed baseline assessments as part of an ongoing, longitudinal study. The primary assessments included the UAB LSA and timed 25-foot walk (T25FW), short physical performance battery (SPPB), global health score (GHS), and geriatric depression scale (GDS) in both OAMS and HCs, and patient determined disease steps (PDDS) scale in only OAMS., Results: OAMS had significantly lower UAB LSA scores than HCs (p < .001). UAB LSA scores had strong correlations with T25FW(r s  = -.641) and SPPB(r s  = 0.507) in OAMS, and moderate correlations in HCs (r s  = -.300 & r s  = 0.384). The correlations between UAB LSA and GHS and GDS scores were significant, but small in OAMS (r s  = -.239 & r s  = -.231), and not statistically significant in HCs (r s  = -.009 & r s  = -.166). There was a strong correlation between UAB LSA and PDDS scores in the OAMS sample (r s  = -.605)., Conclusion: We provided initial evidence for UAB LSA scores as a measure of community mobility in OAMS., Competing Interests: Declaration of Competing Interest This research was supported by a grant from the National Institutes of Health (R01NS109023)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome (ANDS), a rare genetic disease characterized by autism spectrum disorder (ASD), attention deficit/hyperactivity disorder, and speech and motor deficits. The ANKS1B gene encodes for AIDA-1, a protein that is enriched at neuronal synapses and regulates synaptic plasticity. Here we report an unexpected role for oligodendroglial deficits in ANDS pathophysiology. We show that Anks1b-deficient mouse models display deficits in oligodendrocyte maturation, myelination, and Rac1 function, and recapitulate white matter abnormalities observed in ANDS patients. Selective loss of Anks1b from the oligodendrocyte lineage, but not from neuronal populations, leads to deficits in social preference and sensory reactivity previously observed in a brain-wide Anks1b haploinsufficiency model. Furthermore, we find that clemastine, an antihistamine shown to increase oligodendrocyte precursor cell maturation and central nervous system myelination, rescues deficits in social preference in 7-month-old Anks1b-deficient mice. Our work shows that deficits in social behaviors present in ANDS may originate from abnormal Rac1 activity within oligodendrocytes., (© 2023. The Author(s).)

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents. Awake male and female Sprague Dawley rats (postnatal Day 35) received 140 closed-head impacts over the course of a week. Impacted and sham-impacted animals were restrained in a plastic cone, and unrestrained control animals were included to account for effects of restraint and normal development. Animals ( n = 43) underwent repeated diffusion tensor imaging prior to and over 1 month following the final impact. A separate cohort ( n = 53) was assessed behaviourally for fine motor control, emotional-affective behaviour and memory at acute and chronic time points. Histological and immunohistochemical analyses, which were exploratory in nature due to smaller sample sizes, were completed at 1 month following the final impact. All animals tolerated the protocol with no overt changes in behaviour or stigmata of traumatic brain injury, such as alteration of consciousness, intracranial haemorrhage or skull fracture. We detected longitudinal, sex-dependent diffusion tensor imaging changes (fractional anisotropy and axial diffusivity decline) in corpus callosum and external capsule of repetitive subconcussive head impact animals, which diverged from both sham and control. Compared to sham animals, repetitive subconcussive head impact animals exhibited acute but transient mild motor deficits. Repetitive subconcussive head impact animals also exhibited chronic anxiety and spatial memory impairment that differed from the control animals, but these effects were not different from those seen in the sham condition. We observed trends in the data for thinning of the corpus callosum as well as regions with elevated Iba-1 in the corpus callosum and cerebral white matter among repetitive subconcussive head impact animals. While replication with larger study samples is needed, our findings suggest that subconcussive head impacts cause microstructural tissue changes in the developing rat brain, which are detectable with diffusion tensor imaging, with suggestion of correlates in tissue pathology and behaviour. The results point to potential mechanisms underpinning consequences of subconcussive head impacts that have been described in humans. The congruence of our imaging findings with human subconcussive head impacts suggests that neuroimaging could serve as a translational bridge to advance study of injury mechanisms and development of interventions., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated., Objective: Examine apathy and its association with caudate nuclei volume in OAMS and controls. We hypothesized that compared to controls, OAMS would demonstrate: a) greater apathy; b) stronger associations between apathy and caudate nuclei volumes., Methods: OAMS ( n = 67, mean age = 64.55 ± 3.89) and controls ( n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Apathy was assessed through the apathy subscale of the 30-item Geriatric Depression Scale., Results: OAMS reported greater apathy compared to controls ( β = 0.281, p = 0.004). Adjusted moderation analyses revealed a significantly stronger association between caudate volume and apathy (left: B = -1.156, p = 0.039, right: B = -1.163, p = 0.040) among OAMS compared to controls. Conditional effects revealed that in adjusted models, lower volume of both the left ( b = -0.882, p = 0.037) and right ( b = -0.891, p = 0.038) caudate nuclei was significantly associated with greater apathy only among OAMS., Conclusion: Caudate nuclei, which are susceptible to adverse MS effects and implicated in mediating cognitive and motor function, may influence the presence and severity of apathy in OAMS.

Background and Objective: Cognitive and physical functions correlate and delineate aging and disease trajectories. Whereas cognitive reserve (CR) is well-established, physical reserve (PR) is poorly understood. We, therefore, developed and evaluated a novel and more comprehensive construct, individual reserve (IR), comprised of residual-derived CR and PR in older adults with and without multiple sclerosis (MS). We hypothesized that: (a) CR and PR would be positively correlated; (b) low CR, PR, and IR would be associated with worse study outcomes; (c) associations of brain atrophy with study outcomes would be stronger in lower compared to higher IR due to compensatory mechanisms conferred by the latter., Methods: Older adults with MS (n = 66, mean age = 64.48 ± 3.84 years) and controls (n = 66, mean age = 68.20 ± 6.09 years), underwent brain MRI, cognitive assessment, and motoric testing. We regressed the repeatable battery for the assessment of neuropsychological status and short physical performance battery on brain pathology and socio-demographic confounders to derive independent residual CR and PR measures, respectively. We combined CR and PR to define a 4-level IR variable. The oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures., Results: CR and PR were positively correlated. Low CR, PR and IR were associated with worse SDMT and T25FW performances. Reduced left thalamic volume, a marker of brain atrophy, was associated with poor SDMT and T25FW performances only in individuals with low IR. The presence of MS moderated associations between IR and T25FW performance., Conclusion: IR is a novel construct comprised of cognitive and physical dimensions representing collective within-person reserve capacities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood., Objective: Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older persons with and without MS., Methods: Fifty-one older MS patients (age 64.9 ± 3.7 years, 29 women) and 50 healthy, matched controls (66.2 ± 3.2 years, 24 women), participated in the study, which included physical and cognitive test batteries and 3T MRI imaging session. Primary imaging measures were fractional anisotropy (FA) and WM lesion load. The relationship between mobility impairment, defined using a validated short physical performance battery cutoff score, and neuroimaging measures was assessed with stratified logistic regression models. FA was extracted from six fronto-striatal circuits (left/right): dorsal striatum (dStr)-to-anterior dorsolateral prefrontal cortex (aDLPFC), dStr-to-posterior DLPFC, and ventral striatum (vStr)-to-ventromedial prefrontal cortex (VMPFC)., Results: Mobility impairment was significantly associated with lower FA in two circuits, left dStr-aDLPFC ( P  = .003) and left vStr-VMPFC ( P  = .004), in healthy controls but not in MS patients ( P  > .20), for fully adjusted regression models. Conversely, in MS patients but not in healthy controls, mobility impairment was significantly associated with greater lesion volume ( P  < .02)., Conclusions: Comparing older persons with and without MS, we provide compelling evidence of a double dissociation between the presence of mobility impairment and two neuroimaging markers of white matter integrity, fronto-striatal fractional anisotropy, and whole brain lesion load.

Introduction: The objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players., Methods: The sample included 276 active amateur soccer players (196 male and 81 female) aged 18-53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under., Results: We found that soccer players who began heading at age 10 or younger performed better on tests of working memory ( p = 0.03) and verbal learning ( p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups., Discussion: The findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety., Competing Interests: RL reports receiving research support from the NIH, FDA as well as the National Headache Foundation and the Marx Foundation, and receives research support from Allergan/Abbvie, Amgen, Eli Lilly and Electrocore, and receives personal fees as a consultant or advisor from Allergan/Abbvie, Amgen, Biohaven Holdings, Dr. Reddy's, GlaxoSmithKline, Grifols, Lundbeck, Merck, Novartis and Teva Pharmaceuticals, he holds stock or options in Biohaven Holdings and CtrlM Health. In addition, he receives royalties for Wolff's Headache 7th and 8th Edition. ML reports receiving research support from the NIH and Dana Foundation. WS was employed by Medcurio Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Charney, Ye, Fleysher, DeMessie, Stewart, Zimmerman, Kim, Lipton and Lipton.)

Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors are supported by NIH R01 NS123445 ( M.L.L, J.Y.S.) and NIH T32 GM007288 (J.Y.S)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To determine the impact of 12-month heading exposure on short-term learning., Design: A total of 105 active amateur soccer players, 45 women and 60 men, were administered an EMA-based test of working memory, a version of the two-back, once daily for 14 days., Methods: Heading exposure of the participants was assessed using "HeadCount", a validated structured questionnaire at the baseline visits. The short-term rate of learning of each individual is quantified by first fitting a quadratic model to the daily performance on the two-back test over a two-week period, then taking the instantaneous rate of the quadratic function at the 7th test. A linear regression model was used to test the association of heading exposure with rates of learning, including age, sex, years of education and history of concussion as covariates, as well as variables describing soccer play and heading within the two-week period. Sensitivity analyses were performed using different methods for quantifying the learning effects and different transformations on 12-month heading exposure., Results: Greater 12-month heading was associated with lower rates of learning among women (p = 0.008) but not among men (p = 0.74)., Conclusions: We have identified evidence for an adverse, albeit subclinical, effect of soccer heading on brain function among young adult players, which selectively affects women in our sample., (Copyright © 2022 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objectives: To use deep learning of serial portable chest X-ray (pCXR) and clinical variables to predict mortality and duration on invasive mechanical ventilation (IMV) for Coronavirus disease 2019 (COVID-19) patients., Methods: This is a retrospective study. Serial pCXR and serial clinical variables were analyzed for data from day 1, day 5, day 1-3, day 3-5, or day 1-5 on IMV (110 IMV survivors and 76 IMV non-survivors). The outcome variables were duration on IMV and mortality. With fivefold cross-validation, the performance of the proposed deep learning system was evaluated by receiver operating characteristic (ROC) analysis and correlation analysis., Results: Predictive models using 5-consecutive-day data outperformed those using 3-consecutive-day and 1-day data. Prediction using data closer to the outcome was generally better (i.e., day 5 data performed better than day 1 data, and day 3-5 data performed better than day 1-3 data). Prediction performance was generally better for the combined pCXR and non-imaging clinical data than either alone. The combined pCXR and non-imaging data of 5 consecutive days predicted mortality with an accuracy of 85 ± 3.5% (95% confidence interval (CI)) and an area under the curve (AUC) of 0.87 ± 0.05 (95% CI) and predicted the duration needed to be on IMV to within 2.56 ± 0.21 (95% CI) days on the validation dataset., Conclusions: Deep learning of longitudinal pCXR and clinical data have the potential to accurately predict mortality and duration on IMV in COVID-19 patients. Longitudinal pCXR could have prognostic value if these findings can be validated in a large, multi-institutional cohort., (© 2022. The Author(s).)

Background and Purpose: There is limited literature on the prevalence of incidental brain MRI findings in the Hispanic/Latino population, despite their increased prevalence of vascular disease and undertreatment of chronic conditions. The purpose of our study was to determine the prevalence of clinically relevant incidental findings on brain MRI examinations obtained as a part of the Study of Latinos-Investigation of NeuroCognitive Aging MRI (SOL-INCA-MRI) study., Methods: Brain MRI examinations were obtained on 1389 participants in the SOL-INCA-MRI study, a cross-sectional ancillary study of the Hispanic Community Health Study, Study of Latinos, which is a longitudinal, community-based study. Study design of SOL-INCA-MRI involves imaging cognitively normal and participants with mild cognitive impairment. Brain MRI findings were categorized as Level 1 (normal), Level 1.5 (findings of unclear medical significance), Level 2 (potential medical concern), or Level 3 (medically urgent). This article focuses on Level 2 and Level 3 findings., Results: The average age of the sample was 60.8 years (+/- 10.3 years), 66.1% were females. Level 2 and 3 findings were identified in 117 participants, (8.4%), of which 109 (7.8%) were recommended for medical follow-up (Level 2), and 8 (0.6%) were recommended for immediate medical attention (Level 3). Brain MRI findings consisted of chronic infarction in 33 (2.4%), vascular abnormality in 27 (1.9%), intracranial mass in 20 (1.4%), other intracranial findings in 28 (2.0%), and skull base/extracranial findings in 26 (1.9%) patients., Conclusion: Incidental findings of clinical relevance were common among SOL-INCA-MRI participants, but rarely required urgent medical intervention., (© 2021 American Society of Neuroimaging.)

Assessing heading exposure in football is important when exploring the association between heading and brain alterations. To this end, questionnaires have been developed for use in adult populations. However, the validity of self-report in adolescents remains to be elucidated. Male youth soccer players (n = 34) completed a questionnaire on heading exposure after a two-week period, which included matches and training sessions. Self-reported numbers were compared to observation (considered reference). In total, we observed 157 training sessions and 64 matches. Self-reported heading exposure correlated with observed heading exposure (Spearman's rho 0.68; p < 0.001). Players systematically overestimated their heading exposure by a factor of 3 with the random error of 46%. Area under the curve was 0.87 (95% CI 0.67-1) utilizing self-report for identifying players from high- and low-exposure groups. Thus, in this study, self-reported data could be used to group youth players into high and low heading exposure groups, but not to quantify individual heading exposure.

The effects of hormonal contraceptives on structural features of the hypothalamus and pituitary are incompletely understood. One prior study reported microstructural changes in the hypothalamus with oral contraceptive pill (OCP) use. However, effects on hypothalamic volume have not been reported. One prior study reported volumetric changes in the pituitary. However, this study was limited by including participants evaluated for neurological symptoms. We sought to determine if OCP use is associated with alteration of hypothalamic or pituitary volume. High-resolution 3T MRI was performed for a prospective cohort of 50 healthy women from 2016 to 2018, which comprised 21 OCP users (age, 19-29) and 29 naturally cycling women (age, 18-36). Participants were excluded if they were pregnant or had significant medical conditions including neurological, psychiatric, and endocrine disorders. After confirming reliability of the image analysis techniques, 5 raters independently performed manual segmentation of the hypothalamus and semi-automated intensity threshold-based segmentation of the pituitary using ITK-SNAP. Total intracranial volume was estimated using FreeSurfer. A general linear model tested the association of OCP use with hypothalamic and pituitary volumes. Hypothalamic (B = -81.2 ± 24.9, p = 0.002) and pituitary (B = -81.2 ± 38.7, p = 0.04) volumes in OCP users were smaller than in naturally cycling women. These findings may be related to interference with known trophic effects of sex hormones and suggest a structural correlate of central OCP effects., Competing Interests: The authors have declared that no competing interests exist.

The benefits of athletic activity may be attenuated by sport-related head impacts, including soccer-related concussion and subconcussive events. The purpose of this study is to characterize the specific effects of soccer heading on white matter microstructure and cognitive function, independent of concussion, relative to non-athlete controls and relative to active athletes who are not involved in collision sports. 246 amateur soccer players, 72 non-contact/non-collision sports athletes and 110 healthy,non-athlete controls were included in the study, and underwent cognitive testing and 3T diffusion tensor imaging (DTI). Voxelwise linear regression, comparing soccer players and non-contact/non-collision sports athletes healthy,non-athlete controls, identified regions of abnormally low and high fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in athlete participants. Generalized estimating equations were used to examine the effects of 2 week and 1 year heading exposure quartile on cognitive performance and on the volume of each high and each low DTI parameter. Athletes with no or lower exposure to repetitive heading exhibited greater expression of low RD, greater expression of high FA and better performance on tasks of attention, processing speed, verbal memory, and working memory compared to non-athletes. Soccer players with the highest exposure to repetitive head impacts, however, did not differ significantly from healthy, non-athletes on either micro-structural features or cognitive performance, findings not explained by concussion history or demographic factors. These results are consistent with the notion that beneficial effects of athletic conditioning or training on brain structure and function may be attenuated by exposure to repeated subconcussive head impacts.

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor.

Motivation: Many clinical and scientific conclusions that rely on voxel-wise analyses of neuroimaging depend on the accurate comparison of corresponding anatomical regions. Such comparisons are made possible by registration of the images of subjects of interest onto a common brain template, such as the Johns Hopkins University (JHU) template. However, current image registration algorithms are prone to errors that are distributed in a template-dependent manner. Therefore, the results of voxel-wise analyses can be sensitive to template choice. Despite this problem, the issue of appropriate template choice for voxel-wise analyses is not generally addressed in contemporary neuroimaging studies, which may lead to the reporting of spurious results., Results: We present a novel approach to determine the suitability of a brain template for voxel-wise analysis. The approach is based on computing a "distance" between automatically-generated atlases of the subjects of interest and templates that is indicative of the extent of subject-to-template registration errors. This allows for the filtering of subjects and candidate templates based on a quantitative measure of registration quality. We benchmark our approach by evaluating alternative templates for a voxel-wise analysis that reproduces the well-known decline in fractional anisotropy (FA) with age. Our results show that filtering registrations minimizes errors and decreases the sensitivity of voxel-wise analysis to template choice. In addition to carrying important implications for future neuroimaging studies, the developed framework of template induction can be used to evaluate robustness of data analysis methods to template choice., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

Objective: In soccer, unintentional and intentional (heading) head impacts are associated with concussive symptoms and cognitive dysfunction. We examined whether personality traits were associated with these behaviors in soccer players., Design: Cross-sectional study., Setting and Participants: Participants completed study visits at the Albert Einstein College of Medicine. A total of 307 adult amateur soccer players, recruited from New York City and the surrounding area, completed 737 HeadCount-2w questionnaires., Predictor Variables: Personality traits (intellect/imagination, conscientiousness, extraversion, agreeableness, and neuroticism) were assessed with the Mini-International Personality Item Pool questionnaire at the baseline study visit., Main Outcome Measures: Participants completed an online questionnaire (HeadCount-2w) to ascertain frequency of intentional head impacts and occurrence of unintentional head impacts every 3 to 6 months. Generalized estimating equations repeated-measures regressions determined whether personality predicted unintentional and intentional impacts., Results: Personality traits were not associated with unintentional head impact(s) or frequency of intentional head impacts., Conclusions: These findings have important clinical implications, suggesting that personality is not driving the association between high levels of unintentional and intentional head impacts and worse neuropsychological functioning and concussive symptoms.

Soccer is the most popular sport in the world and, since it is a contact sport, players are at risk for head injury, including concussion. Here, we proposed to investigate the association of heading and concussion with macroscopic brain structure among adult amateur soccer players. For this study, 375 amateur soccer players (median age 23 years) completed HeadCount-12m to estimate heading over the 12 months prior to MRI and lifetime concussion. T1-weighted 3D magnetization prepared rapid acquisition gradient echo (MP-RAGE) MRI was performed at 3 Tesla. Parcellation was performed using Freesurfer to extract regional gray and white matter volumes as well as regional cortical thickness and total intracranial volume. Regional cortical brain volumes were normalized by total intracranial volume. We categorized heading into quartiles and concussion as 0, 1 or 2 or more. Generalized linear regressions were used to test the association of heading or concussion with each brain morphometry metric, including age and sex, as covariates. Neither heading nor concussion were associated with reduced brain volume or cortical thickness. We observed that greater heading was associated with greater gray matter volume in the left inferior parietal area, which may reflect effects related to training., Competing Interests: The authors have declared that no competing interests exist.

Objective: Soccer is the most popular sport worldwide and is the only sport where athletes purposely use their head to deflect the ball during play, termed "heading" the ball. These repetitive head impacts (RHI) are associated with worse neuropsychological function; however, factors that can increase risk of injury following exposure to such head impacts have been largely unexamined. The present study provided a novel examination of the modifying role of sleep on the relationship between RHI exposure and neuropsychological function in college-age soccer players., Methods: Fifty varsity and intramural college soccer players completed questionnaires assessing recent and long-term heading exposure, a self-report measure of sleep function, and a battery of neuropsychological tests., Results: A high level of recent heading exposure was significantly associated with poorer processing speed, independent of concussion history. With reduced sleep duration, a high level of recent heading exposure was related to worse sustained attention. However, with greater hours of sleep duration, heading exposure was related to preserved neuropsychological outcome in sustained attention., Conclusions: We replicated our earlier finding of an association between recent head impact exposure and worse processing speed in an independent sample. In addition, we found that sleep may serve as a risk or protective factor for soccer players following extensive exposure to head impacts. Ultimately, this study furthers the understanding of factors impacting neuropsychological function in soccer players and provides empirical support for sleep interventions to help ensure safer soccer play and recovery from injury.

Importance: Emerging evidence suggests that long-term exposure to ball heading in soccer, the most popular sport in the world, confers risk for adverse cognitive outcomes. However, the extent to which the apolipoprotein E ε4 (APOE ε4) allele, a common risk factor for neurodegeneration, and ball heading are associated with cognition in soccer players remains unknown., Objective: To determine whether the APOE ε4 allele and 12-month ball heading exposure are associated with verbal memory in a cohort of adult amateur soccer players., Design, Settings, and Participants: A total of 379 amateur soccer players were enrolled in the longitudinal Einstein Soccer Study from November 11, 2013, through January 23, 2018. Selection criteria included participation in soccer for more than 5 years and for more than 6 months per year. Of the 379 individuals enrolled in the study, 355 were genotyped. Three players were excluded for reporting extreme levels of heading. Generalized estimating equation linear regression models were employed to combine data across visits for a cross-sectional analysis of the data., Exposures: At each study visit every 3 to 6 months, players completed the HeadCount 12-Month Questionnaire, a validated, computer-based questionnaire to estimate 12-month heading exposure that was categorized as low (quartiles 1 and 2), moderate (quartile 3), and high (quartile 4)., Main Outcome and Measures: Verbal memory was assessed at each study visit using the International Shopping List Delayed Recall task from CogState., Results: A total of 352 soccer players (256 men and 96 women; median age, 23 years [interquartile range, 21-28 years]) across a total of 1204 visits were analyzed. High levels of heading were associated with worse verbal memory performance (β = -0.59; 95% CI, -0.93 to -0.25; P = .001). There was no main association of APOE ε4 with verbal memory (β = 0.09; 95% CI, -0.24 to 0.42; P = .58). However, there was a significant association of APOE ε4 and heading with performance on the ISRL task (χ2 = 7.22; P = .03 for overall interaction). In APOE ε4-positive players, poorer verbal memory associated with high vs low heading exposure was 4.1-fold greater (APOE ε4 negative, β = -0.36; 95% CI, -0.75 to 0.03; APOE ε4 positive, β = -1.49; 95% CI, -2.05 to -0.93), and poorer verbal memory associated with high vs moderate heading exposure was 8.5-fold greater (APOE ε4 negative, β = -0.13; 95% CI, -0.54 to 0.29; APOE ε4 positive, β = -1.11, 95% CI, -1.70 to -0.53) compared with that in APOE ε4-negative players., Conclusions and Relevance: This study suggests that the APOE ε4 allele is a risk factor for worse memory performance associated with higher heading exposure in the prior year, which highlights that assessing genetic risks may ultimately play a role in promoting safer soccer play.

The purpose of this study was to examine the potential effect modifying role of the BDNF Val 66 Met polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas. At enrollment and 2 years later, total heading in the prior 12 months (12-mo.) was estimated using an established self-report instrument and diffusion tensor imaging (DTI) was performed. Generalized Estimating Equations (GEE) logistic regression models were employed to test effect modification by the BDNF Val 66 Met polymorphism on the association between 12-mo. heading exposure and DTI. We identified a significant interaction of 12-mo heading * BDNF Val 66 Met genotype on the presence of low Radial Diffusivity, a DTI marker associated with myelination. Only Met (+) players demonstrated significantly reduced odds of low RD [OR (95 % CI): -2.36 (-3.53, -1.19)] associated with the highest vs. lowest quartile of 12-mo heading exposure. BDNF Val 66 Met (+) soccer players with long-term exposure to high levels of heading exhibit less low Radial Diffusivity, suggesting impaired re-myelination may be a substrate of the previously reported association between heading and poor functional outcomes in soccer players., (Copyright © 2019 Hunter, Freudenberg-Hua, Davies, Kim, Fleysher, Stewart, Lipton and Lipton.)

Pacemakers and implantable cardioverter defibrillators are commonly encountered in clinical practice, and entails special consideration when magnetic resonance imaging (MRI) is required. It is estimated that 50-75% of patients with cardiac implantable electronic devices (CIED) will have an indication for MRI during their lifetime. Radiologists may want to recommend MRI or may be consulted about the need to perform MRI in a patient with a CIED, at which point they may need to approve or at least provide guidance as to whether MRI may be performed safely. Even in situations where final clearance will not be provided by the radiologist, he or she can provide valuable information by reviewing radiographs and determining (a) whether a device is MRI-conditional and MRI may ultimately be permitted, (b) is not MRI-conditional and MRI using the standard workflow will therefore not be approved, or (c) when additional information will clearly be required. CIED identification and verification of leads can be accomplished through review of the medical record and/or evaluation of a chest radiograph. In patients with MRI-conditional CIEDs (as well as with legacy CIEDs in those institutions that perform MRI of these patients), specific imaging protocols must be adhered to in order to prevent death or injury to the patient or damage to the device. In this update, we provide details regarding the above topics and provide an algorithm for integrating this information into a clinical workflow to efficiently triage patients with CIEDs who are being considered for MRI., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

When we consider the health and welfare of our children, few issues are of more concern than the risk and consequences of head trauma in sports. From participation in male-dominated football and hockey to girls soccer and softball, repeated impacts to the head that do not produce recognized concussion is the cutting edge of sports head injury research. Our author, a leading researcher in this field, provides the latest on what we know and don't know on this relatively new frontier of neuroscience ., (Copyright 2019 The Dana Foundation All Rights Reserved.)

We aimed to test the hypothesis that the effect of chronic pain on depressive symptoms is mediated through hippocampal volume (HV). Participants were 131 non-demented adults over the age of 70 years from the Einstein Aging Study. Smaller right and left HV were both associated with higher depressive symptoms, but only smaller right HV was associated with chronic pain. In mediation models, right HV was a significant mediator for the effect of chronic pain on depression. Our findings suggest presence of a shared brain substrates between chronic pain and depression as reflected by right HV., (Copyright © 2019. Published by Elsevier B.V.)

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood. Although animal models contribute valuable preclinical information and improve our understanding of the underlying mechanisms following mTBI, only few studies have used diffusion tensor imaging (DTI) to study the evolution of axonal injury following mTBI in rodents. It is known that DTI shows changes after human concussion and the role of delineating imaging findings in animals is therefore to facilitate understanding of related mechanisms. In this work, we used a rodent model of mTBI to investigate longitudinal indices of axonal injury. We present the results of 45 animals that received magnetic resonance imaging (MRI) at multiple time points over a 2-week period following concussive or sham injury yielding 109 serial observations. Overall, the evolution of DTI metrics following concussive or sham injury differed by group. Diffusion tensor imaging changes within the white matter were most noticeable 1 week following injury and returned to baseline values after 2 weeks. More specifically, we observed increased fractional anisotropy in combination with decreased radial diffusivity and mean diffusivity, in the absence of changes in axial diffusivity, within the white matter of the genu corpus callosum at 1 week post-injury. Our study shows that DTI can detect microstructural white matter changes in the absence of gross abnormalities as indicated by visual screening of anatomical MRI and hematoxylin and eosin (H&E)-stained sections in a clinically relevant animal model of mTBI. Whereas additional histopathologic characterization is required to better understand the neurobiological correlates of DTI measures, our findings highlight the evolving nature of the brain's response to injury following concussion., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Electronic stimulation devices are implanted in various locations in the body to decrease pain, modulate nerve function, or stimulate various end organs. The authors describe these devices using a craniocaudal approach, first describing deep brain stimulation (DBS) devices and ending with sacral nerve stimulation (SNS) devices. The radiology-relevant background information for each device and its imaging appearance are also described. These devices have a common design theme and include the following components: (a) a pulse generator that houses the battery and control electronics, (b) an insulated lead or wire that conveys signals to the last component, which is (c) an electrode that contacts the end organ and senses and/or acts on the end organ. DBS electrodes are inserted into various deep gray nuclei, most commonly to treat the symptoms of movement disorders. Occipital, trigeminal, and spinal nerve stimulation devices are used as second-line therapy to control craniofacial or back pain. For cardiac devices, the authors describe two newer devices, the subcutaneous implantable cardioverter defibrillator and the leadless pacemaker, both of which avoid complications related to having leads threaded through the venous system. Diaphragmatic stimulation devices stimulate the phrenic nerve to restore diaphragmatic movement. Gastric electrical stimulation devices act on various parts of the stomach for the treatment of gastroparesis or obesity. Finally, SNS devices are used to modulate urinary and defecatory functions. Common complications diagnosed at imaging include infection, hematoma, lead migration, and lead breakage. Understanding the components, normal function, and normal imaging appearance of each device allows the radiologist to identify complications. © RSNA, 2019.

The underlying mechanisms that result in neurophysiological changes and cognitive sequelae in the context of repetitive mild traumatic brain injury (rmTBI) remain poorly understood. Animal models provide a unique opportunity to examine cellular and molecular responses using histological assessment, which can give important insights on the neurophysiological changes associated with the evolution of brain injury. To better understand the potential cumulative effects of multiple concussions, the focus of animal models is shifting from single to repetitive head impacts. With a growing body of literature on this subject, a review and discussion of current findings is valuable to better understand the neuropathology associated with rmTBI, to evaluate the current state of the field, and to guide future research efforts. Despite variability in experimental settings, existing animal models of rmTBI have contributed to our understanding of the underlying mechanisms following repeat concussion. However, how to reconcile the various impact methods remains one of the major challenges in the field today., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is highly prevalent and there is currently no adequate treatment. Understanding the underlying mechanisms governing TBI and recovery remains an elusive goal. The heterogeneous nature of injury and individual's response to injury have made understanding risk and susceptibility to TBI of great importance. Epidemiologic studies have provided evidence of sex-dependent differences following TBI. However, preclinical models of injury have largely focused on adult male animals. Here, we review 50 studies that have investigated TBI in both sexes using animal models. Results from these studies are highly variable and model dependent, but largely show females to have a protective advantage in behavioral outcomes and pathology following TBI. Further research of both sexes using newer models that better recapitulate mild and repetitive TBI is needed to characterize the nature of sex-dependent injury and recovery, and ultimately identifies targets for enhanced recovery., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diffusion tensor imaging is a magnetic resonance imaging technique that is uniquely capable of detecting microstructural tissue damage in mild and moderate traumatic brain injuries (TBIs). To date, it remains unknown if two common analytic techniques, region of interest (ROI) versus voxel-wise (VW) analyses, detect injury in similar locations. The purpose of this systematic review and meta-analysis was to directly compare the regions of abnormality elucidated by each method. Twenty-seven ROI and 11 VW studies met our inclusion criteria. Our ROI meta-analysis identified 11 regions, including the splenium of the corpus callosum, where fractional anisotropy (FA) was significantly decreased in TBI patients, compared with controls. Likewise, we identified higher mean diffusivity/apparent diffusivity constant in the genu, body, and splenium of the corpus callosum. Alternatively, our VW analysis identified one region of high FA in the right superior longitudinal fasciculus and seven regions of low FA, with the two largest located in the corpus callosum. High mean diffusivity and high radial diffusivity, both in the right inferior longitudinal fasciculus, also was revealed by our VW analysis. Moreover, we have shown that the magnitude of damage in the corpus callosum revealed by ROI analysis (z = -3.15) is greater than that demonstrated by VW analysis (z = -1.41). Overall, this study indicates that both ROI and VW analytic methods are sensitive to low FA in the corpus callosum; however, the ROI method has more power to detect the full extent of tissue abnormality in the corpus callosum. More research utilizing standardized methods and reporting is essential to fully characterize the extent to which ROI and VW analyses can concordantly detect other locations of pathology in mild and moderate TBI patients.

It is now recognized that repetitive head impacts (RHI) in sport have the potential for long-term neurological impairments. In order to identify targets for intervention and/or pharmacological treatment, it is necessary to characterize the neurobiological mechanisms associated with RHI. This review aims to summarize animal and human studies that specifically address Blood Brain Barrier (BBB) dysfunction, abnormal neuro-metabolic and neuro-inflammatory processes as well as Tau aggregation associated with RHI in collision sports. Additionally, we examine the influence of physical activity and genetics on outcomes of RHI, discuss methodological considerations, and provide suggestions for future directions of this burgeoning area of research., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVEThe object of this study was to use diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to characterize the long-term effects of hydrocephalus and shunting on white matter integrity and to investigate the relationship of ventricular size and alterations in white matter integrity with headache and quality-of-life outcome measures.METHODSPatients with shunt-treated hydrocephalus and age- and sex-matched healthy controls were recruited into the study and underwent anatomical and DTI imaging on a 3-T MRI scanner. All patients were clinically stable, had undergone CSF shunt placement before 2 years of age, and had a documented history of complaints of headaches. Outcome was scored based on the Headache Disability Inventory and the Hydrocephalus Outcome Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial, radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the corpus callosum and internal capsule with manual region-of-interest delineation and in other regions with TBSS. Paired t-tests, corrected with a 5% false discovery rate, were used to identify regions with significant differences between patients and controls. Within the patient group, linear regression models were used to investigate the relationship between FA or ventricular volume and outcome, as well as the effect of shunt-related covariates.RESULTSTwenty-one hydrocephalus patients and 21 matched controls completed the study, and their data were used in the final analysis. The authors found significantly lower FA for patients than for controls in 20 of the 48 regions, mostly posterior white matter structures, in periventricular as well as more distal tracts. Of these 20 regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3 showed decreased AD. No areas of increased FA were observed. Higher FA in specific periventricular white matter tracts, tending toward FA in controls, was associated with increased ventricular size, as well as improved clinical outcome.CONCLUSIONSThe study shows that TBSS-based DTI is a sensitive technique for elucidating changes in white matter structures due to hydrocephalus and chronic CSF shunting and provides preliminary evidence that DTI may be a valuable tool for tailoring shunt procedures to monitor ventricular size following shunting and achieve optimal outcome, as well as for guiding the development of alternate therapies for hydrocephalus.

Through a partnership with the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, and Department of Defense, the development of Sport-Related Concussion (SRC) Common Data Elements (CDEs) was initiated. The aim of this collaboration was to increase the efficiency and effectiveness of clinical research studies and clinical treatment outcomes, increase data quality, facilitate data sharing across studies, reduce study start-up time, more effectively aggregate information into metadata results, and educate new clinical investigators. The SRC CDE Working Group consisted of 32 worldwide experts in concussion from varied fields of related expertise divided into three Subgroups: Acute (<72 h post-concussion), Subacute (3 days-3 months post-concussion) and Persistent/Chronic (>3 months post-concussion). To develop CDEs, the Subgroups reviewed various domains, then selected from, refined, and added to existing CDEs, case report forms and field-tested data elements from national registries and funded research studies. Recommendations were posted to the NINDS CDE Website for Public Review from February 2017 to April 2017. Following an internal Working Group review of recommendations, along with consideration of comments received from the Public Review period, the first iteration (Version 1.0) of the NINDS SRC CDEs was completed in June 2017. The recommendations include Core and Supplemental-Highly Recommended CDEs for cognitive data elements and symptom checklists, as well as other outcomes and end-points (e.g., vestibular, oculomotor, balance, anxiety, depression), and sample case report forms (e.g., injury reporting, demographics, concussion history) for domains typically included in clinical research studies. The NINDS SRC CDEs and supporting documents are publicly available on the NINDS CDE website www.commondataelements.ninds.nih.gov . Widespread use of CDEs by researchers and clinicians will facilitate consistent SRC clinical research and trial design, data sharing, and metadata retrospective analysis.

Purpose To examine the role of sex in abnormal white matter microstructure after soccer heading as identified by using the diffusion-tensor imaging (DTI) metric fractional anisotropy (FA). Materials and Methods In this prospective cross-sectional study, 98 individuals who were enrolled in a larger prospective study of amateur soccer players (from 2013 to 2016) were matched 1:1 for age and history of soccer heading in the prior 12 months. Among the subjects, 49 men (mean age, 25.7 years; range, 18-50 years) and 49 women (mean age, 25.8 years; range, 18-50 years) with median total soccer headings per year of 487 and 469, respectively, underwent 3.0-T DTI. Images were registered to the Johns Hopkins University template. A voxelwise linear regression was fitted for FA with terms for the number of headings during the previous 12 months and its interaction with sex after controlling for the following potential confounders: age, years of education, number of lifetime concussions, and handedness. In the resulting statistical maps, P < .01 indicated a statistically significant difference, with a threshold cluster size larger than 100 mm 3 . Results Among men, three regions were identified in which greater heading exposure was associated with lower FA; eight such regions were identified among women (>100 contiguous voxels, P < .01). In seven of the eight regions identified in women, the association between heading and FA was stronger in women than in men. There was no significant difference of heading with FA between the sexes for any region in which heading was associated with FA among men (P > .01, <100 contiguous voxels). Conclusion With similar exposure to heading, women exhibit more widespread evidence of microstructural white matter alteration than do men, suggesting preliminary support for a biologic divergence of brain response to repetitive trauma. © RSNA, 2018 Online supplemental material is available for this article.

Purpose: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives., Methods: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA., Results: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses., Conclusions: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

The effects of soccer-related head impacts, beyond overt concussions, on Patient Reported Outcomes (PROs) have not been explored to date. Generalized estimating equations were employed to determine the association between soccer-related head impacts (headers in the prior 2 weeks, unintentional head impacts in the prior 2 weeks, headers in the prior 12 months and lifetime concussions) on PROs including depression, anxiety, sleep disturbance and sleep impairment. Compared to players with no unintentional head impacts in the prior 2 weeks, players with one unintentional exposure reported more symptoms of anxiety (p = 0.002) and players with 2+ exposures reported more symptoms of depression (p = 0.006) and anxiety (p < 0.001). In contrast, players in the 3rd Quartile of 12 mo. headers reported less anxiety (p = 0.001), sleep disturbance (p = 0.002) and sleep impairment (p < 0.001) compared to those in the 1st quartile. Unintentional head impacts are associated with worse PROs while more headers are paradoxically associated with better PROs.

Background and Purpose: Neurodegeneration after mild traumatic brain injury may manifest as decreasing regional brain volume that evolves from months to years following mild traumatic brain injury and is associated with worse clinical outcomes. We hypothesized that quantitative brain volume derived from CT of the head, performed for clinical indications during routine care, would change with time and provide insights into the putative neuroinflammatory response to mild traumatic brain injury., Materials and Methods: We searched the electronic medical record of our institution for NCCTs of the head performed in patients with mild traumatic brain injury and included those who also underwent NCCTs of the head 1 month to 1 year before and after mild traumatic brain injury for an indication unrelated to trauma. Controls underwent 3 sequential NCCTs of the head with indications unrelated to trauma. The whole-brain and intracranial volume groups were computed using ITK-SNAP. Brain volumes normalized to intracranial volumes were compared across time points using the Wilcoxon signed-rank test., Results: We identified 48 patients from 2005 to 2015 who underwent NCCTs of the head in the emergency department for mild traumatic brain injury and had NCCTs of the head performed both before and after mild traumatic brain injury. Median normalized brain volumes significantly decreased on the follow-up study post-mild traumatic brain injury (0.86 versus 0.84, P < .001) and were similar compared with pre-mild traumatic brain injury studies (0.87 versus 0.86, P = .927). There was no significant difference between normalized brain volumes in the 48 controls., Conclusions: A decrease in brain volume following mild traumatic brain injury is detectable on CT and is not seen in similar patients with non-mild traumatic brain injury during a similar timeframe. Given the stability of brain volume before mild traumatic brain injury, CT volume loss may represent the subtle effects of neurodegeneration., (© 2018 by American Journal of Neuroradiology.)

Objective: Compared to heading, unintentional head impacts (e.g., elbow to head, head to head, head to goalpost) in soccer are more strongly related to risk of moderate to very severe Central Nervous System (CNS) symptoms. But, most head impacts associated with CNS symptoms that occur in soccer are mild and are more strongly related to heading. We tested for a differential relation of heading and unintentional head impacts with neuropsychological (NP) test performance., Method: Active adult amateur soccer players were recruited in New York City and the surrounding areas for this repeated measures longitudinal study of individuals who were enrolled if they had 5+ years of soccer play and were active playing soccer 6+ months/year. All participants completed a baseline validated questionnaire ("HeadCount-2w"), reporting 2-week recall of soccer activity, heading and unintentional head impacts. In addition, participants also completed NP tests of verbal learning, verbal memory, psychomotor speed, attention, and working memory. Most participants also completed one or more identical follow-up protocols (i.e., HeadCount-2w and NP tests) at 3- to 6-month intervals over a 2-year period. Repeated measures General Estimating Equations (GEE) linear models were used to determine if variation in NP tests at each visit was related to variation in either heading or unintentional head impacts in the 2-week period before testing., Results: 308 players (78% male) completed 741 HeadCount-2w. Mean (median) heading/2-weeks was 50 (17) for men and 26 (7) for women. Heading was significantly associated with poorer performance on psychomotor speed ( p  < 0.001) and attention ( p  = 0.02) tasks and was borderline significant with poorer performance on the working memory ( p  = 0.06) task. Unintentional head impacts were not significantly associated with any NP test. Results did not differ after excluding 22 HeadCount-2w with reported concussive or borderline concussive symptoms., Conclusion: Poorer NP test performance was consistently related to frequent heading during soccer practice and competition in the 2 weeks before testing. In contrast, unintentional head impacts incurred during soccer were not related to cognitive performance.

Objectives: To validate the HeadCount-2w questionnaire for estimation of 2-week soccer heading by comparison to daily electronic diary reporting over the same two-week period., Design: Prospective observational study., Methods: Adult amateur soccer players completed HeadCount-daily, comprising 14 daily at-home assessments of soccer play and heading via a tablet PC. Following the 14day period, players completed HeadCount-2w, a web-based two-week-recall questionnaire on soccer and heading. intraclass correlation coefficient (ICC) was estimated between HeadCount-daily, the reference standard, and HeadCount-2w estimates of heading during the same 2-week period., Results: 53 participants (38 men) reported a mean of 24.36 (median=11.76) headers during 2 weeks via HeadCount-daily and a mean of 38.34 (median=15.0) headers for the same 2 weeks via HeadCount-2w. The ICC comparing 2-week heading from HeadCount-daily and HeadCount-2w was 0.85. Linear regression of the log-transformed Headcount-daily on HeadCount-2w data yielded a slope of 0.71 (p<0.001; 95% CI 0.54-0.82), suggesting that heading tends to be over-estimated by HeadCount-2w relative to HeadCount-daily. Slope estimates for men (0.65) and women (0.71) were similar., Conclusions: HeadCount, a self-administered web-based survey, is valid for self-reporting 2-week heading in adult amateur players, supporting its use in future research and as a simple and low-cost technique for exposure monitoring., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)