Associations between repetitive head impact exposure and midlife mental health wellbeing in former amateur athletes.

Introduction: Repetitive head impacts (RHI) have been suggested to increase the risk of developing a neurodegenerative disease, and many of these individuals develop a preceding mental health diagnosis. Given the lack of studies among amateur athletes, this study aimed to examine mental health outcomes in middle-aged amateur athletes who have been exposed to RHI through contact sport participation. Methods: This is a single site, cohort study involving former amateur athletes aged between 30 and 60 with at least 10 years of organized contact or non-contact sport participation. All participants completed demographic and mental health questionnaires. Mental health outcomes included symptoms related to depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit hyperactive disorder (ADHD), and aggression. Self-reported data on mental health diagnoses and associated prescription were elicited and used to estimate odds ratios (OR). Results: Data from 41 contact athletes and 22 age/sex-matched non-contact athletes were available for analysis. The contact group exhibited a 2.25-fold higher likelihood of being diagnosed with mental health disorders and 1.29-fold higher likelihood of using associated medications compared to the non-contact group. The contact group reported significantly higher PTSD-related symptoms [4.61 (0.03,9.2), p=0.05] compared to the non-contact control group. While not statistically significant, the contact group showed increased depressive [2.37 (0.05, 4.79), p=0.07] and ADHD symptoms [4.53 (0.51, 9.57), p=0.08] compared to controls. In a secondary analysis, a distinct trend emerged within the contact group, revealing pronounced elevations in mental health symptoms among individuals with lower socioeconomic status (<$50,000/year) compared to higher income subgroups, and these symptoms decreased as income levels rose [depression: -3.08 (-4.47, -1.7), p<0.001; anxiety: -1.95 (-3.15, -0.76), p=0.002; ADHD: -4.99 (-8.28, -1.69), p=0.004; PTSD: -4.42 (-7.28, -1.57), p=0.003; aggression: -6.19 (-11.02, -1.36), p=0.01]. This trend was absent in the non-contact control group. Discussion: Our data suggest that even individuals at the amateur level of contact sports have an increased likelihood of being diagnosed with mental health disorders or experiencing mental health symptoms compared to non-contact athletes. Our findings indicate that socioeconomic status may have an interactive effect on individuals' mental health, particularly among those with a long history of RHI exposure.

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

Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes. Glial fibrillary acidic protein (GFAP) changes were correlated with three measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 h before (T1) to 48 h after (T3) the game. To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5 ± 1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs. 91.95 pg/mL, p = 0.008) and from T0 to T2 (mean 79.69 vs. 99.21 pg/mL, p < 0.001). WM integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% confidence interval [CI]: -2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus and with increased MD in the right fornix (r-values ranged from 0.59 to 0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics (r-values ranged from 0.69 to 0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurological response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Owing to the small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.

Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials.

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.

An approach for the analysis of axonal neuroinflammation by measuring dual biomarkers of oligodendrocytes and inflammatory cytokine in human plasma.

The myelin sheath surrounding axons is vulnerable to mechanical stresses after head injuries, as well as autoimmune attacks and degeneration in neurological disorders. Unfortunately, there is currently no effective method to assess these axonal conditions in individual patients. We have developed a sandwich immunoassay detecting dual signals of myelin oligodendrocyte glycoprotein (MOG) and interleukin 1B (IL1B) in human plasma ([IL1B on MOG]). While IL1B is one of common inflammation markers, its lack of tissue specificity is addressed by identifying IL1B on extracellular vesicles from oligodendrocytes isolated using anti-MOG, suggesting inflammation around axons. In 77 control subjects, plasma levels of [IL1B on MOG] did not increase more than 2 fold from baseline. During the sports season, 14% (151 football players) and 22% (18 rugby players) exhibited a substantial 2-17 fold increase, despite the absence of traumatic brain injuries. This elevation demonstrated a non-random pattern, with some individuals gradually rising towards the season's end, followed by a decline. [IL1B on MOG] levels also correlated with the clinical course of a post-concussion syndrome case. These data indicate that [IL1B on MOG] blood test is a potential marker for assessing mild axonal neuroinflammation.

Cerebral Cortical Surface Structure and Neural Activation Pattern Among Adolescent Football Players.

Importance: Recurring exposure to head impacts in American football has garnered public and scientific attention, yet neurobiological associations in adolescent football players remain unclear. Objective: To examine cortical structure and neurophysiological characteristics in adolescent football players. Design, Setting, and Participants: This cohort study included adolescent football players and control athletes (swimming, cross country, and tennis) from 5 high school athletic programs, who were matched with age, sex (male), and school. Neuroimaging assessments were conducted May to July of the 2021 and 2022 seasons. Data were analyzed from February to November 2023. Exposure: Playing tackle football or noncontact sports. Main Outcomes and Measures: Structural magnetic resonance imaging (MRI) data were analyzed for cortical thickness, sulcal depth, and gyrification, and cortical surface-based resting state (RS)-functional MRI analyses examined the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and RS-functional connectivity (RS-FC). Results: Two-hundred seventy-five male participants (205 football players; mean [SD] age, 15.8 [1.2] years; 5 Asian [2.4%], 8 Black or African American [3.9%], and 189 White [92.2%]; 70 control participants; mean [SD] age 15.8 [1.2] years, 4 Asian [5.7], 1 Black or African American [1.4%], and 64 White [91.5%]) were included in this study. Relative to the control group, the football group showed significant cortical thinning, especially in fronto-occipital regions (eg, right precentral gyrus: t = -2.24; P = .01; left superior frontal gyrus: -2.42; P = .002). Elevated cortical thickness in football players was observed in the anterior and posterior cingulate cortex (eg, left posterior cingulate cortex: t = 2.28; P = .01; right caudal anterior cingulate cortex 3.01; P = .001). The football group had greater and deeper sulcal depth than the control groups in the cingulate cortex, precuneus, and precentral gyrus (eg, right inferior parietal lobule: t = 2.20; P = .004; right caudal anterior cingulate cortex: 4.30; P < .001). Significantly lower ALFF was detected in the frontal lobe and cingulate cortex of the football group (t = -3.66 to -4.92; P < .01), whereas elevated ALFF was observed in the occipital regions (calcarine and lingual gyrus, t = 3.20; P < .01). Similar to ALFF, football players exhibited lower ReHo in the precentral gyrus and medial aspects of the brain, such as precuneus, insula, and cingulum, whereas elevated ReHo was clustered in the occipitotemporal regions (t = 3.17; P < .001; to 4.32; P < .01). There was no group difference in RS-FC measures. Conclusions and Relevance: In this study of adolescent athletes, there was evidence of discernible structural and physiological differences in the brains of adolescent football players compared with their noncontact controls. Many of the affected brain regions were associated with mental health well-being.

Blood biomarkers of neuronal injury in paediatric cerebral malaria and severe malarial anaemia.

Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders. In paediatric severe malaria, elevated tau is associated with mortality and neurocognitive complications. We aimed to investigate whether a multi-analyte panel including ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein can serve as biomarkers of brain injury associated with mortality and neurodisability in cerebral malaria and severe malarial anaemia. In a prospective cohort study of Ugandan children, 18 months to 12 years of age with cerebral malaria (n = 182), severe malarial anaemia (n = 158), and asymptomatic community children (n = 118), we measured admission blood levels of ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein. We investigated differences in biomarker levels, associations with mortality, blood-brain barrier integrity, neurodeficits and cognitive Z-scores in survivors up to 24-month follow-up. Admission ubiquitin C-terminal hydrolase-L1 levels were elevated >95th percentile of community children in 71 and 51%, and neurofilament-light chain levels were elevated >95th percentile of community children in 40 and 37% of children with cerebral malaria and severe malarial anaemia, respectively. Glial fibrillary acidic protein was not elevated in disease groups compared with controls. In cerebral malaria, elevated neurofilament-light chain was observed in 16 children who died in hospital compared with 166 survivors (P = 0.01); elevations in ubiquitin C-terminal hydrolase-L1 levels were associated with degree of blood-brain barrier disruption (P = 0.01); and the % predictive value for neurodeficits over follow-up (discharge, 6-, 12-, and 24 months) increased for ubiquitin C-terminal hydrolase-L1 (60, 67, 72, and 83), but not neurofilament-light chain (65, 68, 60, and 67). In cerebral malaria, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse memory scores in children <5 years at malaria episode who crossed to over 5 years old during follow-up cognitive testing [ß -1.13 (95% confidence interval -2.05, -0.21), P = 0.02], and elevated neurofilament-light chain was associated with worse attention in children ≥5 years at malaria episode and cognitive testing [ß -1.08 (95% confidence interval -2.05, -1.05), P = 0.03]. In severe malarial anaemia, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse attention in children <5 years at malaria episode and cognitive testing [ß -0.42 (95% confidence interval -0.76, -0.07), P = 0.02]. Ubiquitin C-terminal hydrolase-L1 and neurofilament-light chain levels are elevated in paediatric cerebral malaria and severe malarial anaemia. In cerebral malaria, elevated neurofilament-light chain is associated with mortality whereas elevated ubiquitin C-terminal hydrolase-L1 is associated with blood-brain barrier dysfunction and neurodeficits over follow-up. In cerebral malaria, both markers are associated with worse cognition, while in severe malarial anaemia, only ubiquitin C-terminal hydrolase-L1 is associated with worse cognition.

Neuro-ophthalmologic and blood biomarker responses in ADHD following subconcussive head impacts: a case-control trial.

Introduction: This clinical trial aimed to determine the influence of attention-deficit/hyperactivity disorder (ADHD) on neuro-ophthalmologic function and brain-derived blood biomarkers following acute subconcussive head impacts. Methods: The present trial consisted of age- and sex-matched samples with a ratio of 1:1 between two groups with a total sample size of 60 adults (age ± SD; 20.0 ± 1.8 years). Soccer players diagnosed with and medicated daily for ADHD were assigned into an ADHD group (n = 30). Soccer players without ADHD were assigned into a non-ADHD group (n = 30). Participants performed 10 soccer headers with a soccer ball projected at a velocity of 25mph. King-Devick test (KDT), near point of convergence (NPC), and serum levels of NF-L, tau, GFAP, and UCH-L1 were assessed at baseline (pre-heading) and at 2 h and 24 h post-heading. Results: There were no statistically significant group-by-time interactions in outcome measures. However, at baseline, the ADHD group exhibited lower neuro-ophthalmologic functions compared to the non-ADHD group (NPC: p = 0.019; KDT: p = 0.018), and persisted at 2 h-post (NPC: p = 0.007; KDT: p = 0.014) and 24 h-post heading (NPC: p = 0.001). NPC significantly worsened over time in both groups compared to baseline [ADHD: 2 h-post, 1.23 cm, 95%CI:(0.77, 1.69), p < 0.001; 24 h-post, 1.68 cm, 95%CI:(1.22, 2.13), p = 0.001; Non-ADHD: 2 h-post, 0.96 cm, 95%CI:(0.50, 1.42), p < 0.001; 24 h-post, 1.09 cm, 95%CI:(0.63, 1.55), p < 0.001]. Conversely, improvements in KDT time compared to baseline occurred at 2 h-post in the non-ADHD group [-1.32 s, 95%CI:(-2.55, -0.09), p = 0.04] and at 24 h-post in both groups [ADHD: -4.66 s, 95%CI:(-5.89, -3.43), p < 0.001; Non-ADHD: -3.46 s, 95%CI:(-4.69, -2.23), p < 0.001)]. There were no group-by-time interactions for GFAP as both groups exhibited increased levels at 2 h-post [ADHD: 7.75 pg./mL, 95%CI:(1.41, 14.10), p = 0.019; Non-ADHD: 7.91 pg./mL, 95%CI:(1.71, 14.14), p = 0.015)] that returned to baseline at 24 h-post. NF-L levels increased at 2 h-post heading in the ADHD group [0.45 pg./mL, 95%CI:(0.05, 0.86), p = 0.032], but no significant NF-L changes were observed in the non-ADHD group over time. Discussion: Ten soccer headers elevated GFAP levels and NPC impairment in both groups. However, persisting group difference in NPC, blunted KDT performance, and increased NF-L levels in the ADHD group suggest that ADHD may reduce neuro-ophthalmologic function and heighten axonal response to soccer headers. Clinical trial registration: ClinicalTrials.gov, identifier ID: (NCT04880304).

Updated beliefs and shaken confidence: evidence from vaccine hesitancy caused by experiencing "COVID arm".

BACKGROUND: Public health depends largely on people's knowledge, beliefs, or behaviors regarding their health and medical treatments. Although works based on the health belief model have shown that public beliefs about medical treatments affect willingness to take the treatments, little is known about the effects of changes in beliefs on attitudes toward treatment. How one's past experiences relate to one's beliefs about a given medical treatment is worth considering. METHODS: We implemented an online panel survey in February 2021 and March 2022 in Japan before and after COVID-19 vaccines were administered to the public within the country. We exploited delayed localized hypersensitivity reactions to COVID-19 vaccines, namely, "COVID arm", as an exogenous shock to investigate the relationship between past negative experiences and current beliefs about medical treatments or science. "COVID arm" was an unexpected side effect and thus likely caused updated beliefs about the vaccine. Out of the nonprobability sample of 15,000 respondents in the first wave in February 2021, 9,668 respondents also responded to the second wave conducted in March 2022. Outcome variables were whether experiencing "COVID arm" affected the respondents' 1) confidence in vaccine safety, 2) willingness to take the next dose of COVID-19 vaccines, 3) acknowledgment of the importance of vaccination, and 4) confidence in science. We measured the impact of experience with "COVID arm" on changes in the probability that survey respondents would respond affirmatively to questions posed about the issues listed above. RESULTS: Experiencing "COVID arm" significantly lowered confidence in the safety of vaccination by 4.3 percentage points, which was approximately 6% of the sample mean for the first wave, and lowered the probability of taking a second dose of the COVID-19 vaccine by 1.5 percentage points. These adverse impacts were observed after conditioning background characteristics and prior confidence in vaccination. Experiencing "COVID arm" affected neither the acknowledged importance of vaccination nor confidence in science in a statistically significant way. CONCLUSIONS: An unexpected and uncomfortable shock regarding beliefs about a treatment decreases willingness to take the treatment. An appropriate public health policy should account for this effect. TRIAL REGISTRATION: The survey was preregistered with the American Economic Association's RCT Registry (Fukai et al., 2022).

Structural brain morphology in young adult women who have been choked/strangled during sex: A whole-brain surface morphometry study.

INTRODUCTION: Being choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed to characterize neuroanatomical differences between young adult women (18-30 years old) who were exposed to frequent sexual choking and their choking naïve controls. METHODS: This cross-sectional study consisted of two groups (choking [≥4 times in the past 30 days] vs. choking-naïve group). Participants who reported being choked four or more times during sex in the past 30 days were enrolled in the choking group, whereas those without were assigned to the choking naïve group. High-resolution anatomical magnetic resonance imaging (MRI) data were analyzed using both volumetric features (cortical thickness) and geometric features (fractal dimensionality, gyrification, sulcal depth). RESULTS: Forty-one participants (choking n = 20; choking-naïve n = 21) contributed to the final analysis. The choking group showed significantly increased cortical thickness across multiple regions (e.g., fusiform, lateral occipital, lingual gyri) compared to the choking-naïve group. Widespread reductions of the gyrification were observed in the choking group as opposed to the choking-naïve group. However, there was no group difference in sulcal depth. The fractal dimensionality showed bi-directional results, where the choking group exhibited increased dimensionality in areas including the postcentral gyrus, insula, and fusiform, whereas decreased dimensionality was observed in the bilateral superior frontal gyrus and pericalcarine cortex. CONCLUSION: These data in cortical morphology suggest that sexual choking events may be associated with neuroanatomical alteration. A longitudinal study with multimodal assessment is needed to better understand the temporal ordering of sexual choking and neurological outcomes.

The modulatory role of cannabis use in subconcussive neural injury.

Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group. There was no group difference in serum neurofilament light levels at any time point. Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings.

Longitudinal Associations of Clinical and Biochemical Head Injury Biomarkers With Head Impact Exposure in Adolescent Football Players.

Importance: Consequences of subconcussive head impacts have been recognized, yet most studies to date have included small samples from a single site, used a unimodal approach, and lacked repeated testing. Objective: To examine time-course changes in clinical (near point of convergence [NPC]) and brain-injury blood biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], and neurofilament light [NF-L]) in adolescent football players and to test whether changes in the outcomes were associated with playing position, impact kinematics, and/or brain tissue strain. Design, Setting, and Participants: This multisite, prospective cohort study included male high school football players aged 13 to 18 years at 4 high schools in the Midwest during the 2021 high school football season (preseason [July] and August 2 to November 19). Exposure: A single football season. Main Outcomes and Measures: The main outcomes were NPC (a clinical oculomotor test) and serum levels of GFAP, UCH-L1, and NF-L. Participants' head impact exposure (frequency and peak linear and rotational accelerations) was tracked using instrumented mouthguards, and maximum principal strain was computed to reflect brain tissue strain. Players' neurological function was assessed at 5 time points (preseason, post-training camp, 2 in season, and postseason). Results: Ninety-nine male players contributed to the time-course analysis (mean [SD] age, 15.8 [1.1] years), but data from 6 players (6.1%) were excluded from the association analysis due to issues related to mouthguards. Thus, 93 players yielded 9498 head impacts in a season (mean [SD], 102 [113] impacts per player). There were time-course elevations in NPC and GFAP, UCH-L1, and NF-L levels. Compared with baseline, the NPC exhibited a significant elevation over time and peaked at postseason (2.21 cm; 95% CI, 1.80-2.63 cm; P < .001). Levels of GFAP and UCH-L1 increased by 25.6 pg/mL (95% CI, 17.6-33.6 pg/mL; P < .001) and 188.5 pg/mL (95% CI, 145.6-231.4 pg/mL; P < .001), respectively, later in the season. Levels of NF-L were elevated after the training camp (0.78 pg/mL; 95% CI, 0.14-1.41 pg/mL; P = .011) and midseason (0.55 pg/mL; 95% CI, 0.13-0.99 pg/mL; P = .006) but normalized by the end of the season. Changes in UCH-L1 levels were associated with maximum principal strain later in the season (0.052 pg/mL; 95% CI, 0.015-0.088 pg/mL; P = .007) and postseason (0.069 pg/mL; 95% CI, 0.031-0.106 pg/mL; P < .001). Conclusions and Relevance: The study data suggest that adolescent football players exhibited impairments in oculomotor function and elevations in blood biomarker levels associated with astrocyte activation and neuronal injury throughout a season. Several years of follow-up are needed to examine the long-term effects of subconcussive head impacts in adolescent football players.

Association Between Head Impact Exposure, Psychological Needs, and Indicators of Mental Health Among U.S. High School Tackle Football Players.

PURPOSE: Age of first exposure to tackle football and head impact kinematics have been used to examine the effect of head impacts on mental health outcomes. These measures coupled with retrospective and cross-sectional designs have contributed to conflicting results. The purpose of this study was to identify the effect of one season of head impact exposure, age of first exposure to football, and psychological need satisfaction on acute mental health outcomes in adolescent football players. METHODS: This prospective single-season cohort study used sensor-installed mouthguards to collect head impact exposure along with surveys to assess age of first exposure to football, psychological satisfaction, depressive symptoms, anxiety symptoms, and thriving from football players at four high schools (n = 91). Linear regression was used to test the association of head impact exposure, age of first exposure, and psychological satisfaction with acute mental health outcomes. RESULTS: A total of 9,428 impacts were recorded with a mean of 102 ± 113 impacts/player. Cumulative head impact exposure and age of first exposure were not associated with acute mental health outcomes at postseason or change scores from preseason to postseason. Greater psychological satisfaction was associated with fewer depressive symptoms (ß = -0.035, SE = 0.008, p = < .001), fewer anxiety symptoms (ß = -0.021, SE = 0.008, p = .010), and greater thriving scores (ß = 0.278, SE = 0.040, p = < .001) at postseason. DISCUSSION: This study does not support the premise that greater single-season head impact exposure or earlier age of first exposure to tackle football is associated with worse acute mental health indicators over the course of a single season in adolescent football players.

Association Between Serum Neurofilament Light and Glial Fibrillary Acidic Protein Levels and Head Impact Burden in Women's Collegiate Water Polo.

Recent investigations have identified water polo athletes as at risk for concussions and repetitive subconcussive head impacts. Head impact exposure in collegiate varsity women's water polo, however, has not yet been longitudinally quantified. We aimed to determine the relationship between cumulative and acute head impact exposure across pre-season training and changes in serum biomarkers of brain injury. Twenty-two Division I collegiate women's water polo players were included in this prospective observational study. They wore sensor-installed mouthguards during all practices and scrimmages during eight weeks of pre-season training. Serum samples were collected at six time points (at baseline, before and after scrimmages during weeks 4 and 7, and after the eight-week pre-season training period) and assayed for neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) using Simoa® Human Neurology 2-Plex B assay kits. Serum GFAP increased over time (e.g., an increase of 0.6559 pg/mL per week; p = 0.0087). Neither longitudinal nor acute pre-post scrimmage changes in GFAP, however, were associated with head impact exposure. Contrarily, an increase in serum NfL across the study period was associated with cumulative head impact magnitude (sum of peak linear acceleration: B = 0.015, SE = 0.006, p = 0.016; sum of peak rotational acceleration: B = 0.148, SE = 0.048, p = 0.006). Acute changes in serum NfL were not associated with head impacts recorded during the two selected scrimmages. Hormonal contraceptive use was associated with lower serum NfL and GFAP levels over time, and elevated salivary levels of progesterone were also associated with lower serum NfL levels. These results suggest that detecting increases in serum NfL may be a useful way to monitor cumulative head impact burden in women's contact sports and that female-specific factors, such as hormonal contraceptive use and circulating progesterone levels, may be neuroprotective, warranting further investigations.

Association of Frequent Sexual Choking/Strangulation With Neurophysiological Responses: A Pilot Resting-State fMRI Study.

Being choked or strangled during partnered sex is an emerging sexual behavior, prevalent among young adult women. The goal of this study was to test whether, and to what extent, frequently being choked or strangled during sex is associated with cortical surface functioning and functional connectivity. This case-control study consisted of two groups (choking vs. choking-naïve). Women who were choked 4 or more times during sex in the past 30 days were enrolled into the choking group, whereas those without were assigned to the choking-naïve group. We collected structural and resting-state functional magnetic resonance imaging (fMRI) data and analyzed the data for amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) using cortical surface-based resting-state fMRI analysis, followed by static and dynamic resting-state fMRI connectivity analysis. Forty-one participants (choking n = 20; choking-n-aïve n = 21) contributed to the analysis. An inter-hemispheric imbalance in neuronal activation pattern was observed in the choking group. Specifically, we observed significantly lower ALFF and ReHo in the left cortical regions (e.g., angular gyrus, orbitofrontal gyrus) and higher ALFF and ReHo in the right cortical regions (e.g., pre-central/post-central gyri) in the choking group compared with the choking-naïve group. A significant group difference was found in static functional connectivity between the bilateral angular gyrus and the whole brain, in which the choking group's angular gyrus showed hyperconnectivity with, for example, the post-central gyrus, pre-central gyrus, and Rolandic operculum, relative to the choking-naïve group. The dynamic analysis revealed hyperconnectivity between the left angular gyrus and the bilateral postcentral gyrus in the choking group compared with the choking-naïve group. Taken together, our data show that multiple experiences of sexual choking/strangulation are associated with an inter-hemispheric imbalance in neural activation pattern and hyperconnectivity between the angular gyrus and brain regions related to motor control, consciousness, and emotion. A longitudinal study using multi-modal neurological assessments is needed to clarify the acute and chronic consequences of sexual choking/strangulation.

Effects of Physical Exertion on Early Changes in Blood-Based Brain Biomarkers: Implications for the Acute Point of Care Diagnosis of Concussion.

Blood-based brain biomarkers (BBM) such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have potential to aid in the diagnosis of concussion. Recently developed point-of-care test devices would enable BBMs to be measured in field settings such military and sport environments within minutes of a suspicious head hit. However, head hits in these environments typically occur in the setting of vigorous physical exertion, which can itself increase BBMs levels. Thus, efforts to develop BBMs as acute concussion aids in field settings need to account for the effects of physical exertion. To determine the acute effects of physical exertion on the BBMs, we measured GFAP, UCH-L1, tau, and neurofilament light chain (NF-L) immediately before, immediately after, and 45 min after a single workout session consisting of aerobic and resistance exercises in 30 collegiate football players. Subjects wore body sensors measuring several aspects of exertion and underwent diffusion tensor imaging 24 h before and 48 h after exertion. All subjects were male with a mean age of 19.5 ± 1.2 years. The mean duration of activity during the workout session was 94 ± 31 min. There was a significant decrease in serum GFAP immediately after (median decrease of 27.76%, p < 0.0001) and a significant increase in serum UCH-L1 45 min after (median increase of 37.11%, p = 0.016) exertion, compared with pre-exertion baseline. No significant changes in tau or NF-L were identified. The duration of exertion had a significant independent linear correlation to the increase in serum UCHL1 from pre-exertion to 45 min after exertion (r = 0.68, p = 0.004). There were no significant pre- to post-exertional changes in any of the 39 examined brain white matter regions, and biomarker changes did not correlate to variation in white matter integrity in any of these regions. Thus, exertion appeared to be associated with immediate decreases in serum GFAP and very acute (45 min) increases in UCH-L1. These changes were related to the duration of exertion, but not to changes in brain white matter integrity. Our results have important implications for how these BBMs might be used to aid in the on-scene diagnosis of concussion occurring in the setting of physical exertion.

Monitoring of Post-Brain Injuries By Measuring Plasma Levels of Neuron-Derived Extracellular Vesicles.

Background: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury. Methods: A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 + CD9+]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36). Results: The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 + CD9+]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within a ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly (P = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23). Conclusions: The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.

The association between contact sport exposure and cervical sensorimotor dysfunction: a scoping review of implications for future musculoskeletal injury risk.

BACKGROUND: While morphological changes to the cervical spine have been observed for over 40 years in response to contact sport participation, little is known about the secondary effects of the cervical impairment on future musculoskeletal injury and disability. OBJECTIVES AND DESIGN: A scoping review was performed to discuss the relationship between contact sport participation and morphological changes to the cervical spine. Moreover, the correlation between morphological changes in the musculoskeletal structures of the cervical spine and resultant deficits in cervical sensorimotor and neuromotor function are discussed. Lastly, how alterations in cervical sensorimotor function may affect overall risk of musculoskeletal injury is discussed. METHODS: The scientific literature was searched in PubMed, Sport Discus, and Web of Science pertaining to contact-sport athletes and/or cervical pathology and the cervicocephalic network. The Asksey and O'Malley's framework and PRISMA for Scoping Reviews were used to conduct and report the following review. Included articles were grouped into three categories: (1) Morphological changes to the cervical spine in contact sport athletes. (2) The role of the neuromotor pathways of the cervical spine in maintenance of postural tone and coordination of the extremities. (3) The correlation between altered cervical sensorimotor function and a resultant increase in musculoskeletal injury risk. RESULTS: Our search identified 566 documents, of which 405 underwent full-text screening, resulting in 54 eligible studies for the review. Widespread cervical sensorimotor dysfunction was observed in contact sport athletes. Independently, cervical sensorimotor function was demonstrated to play a critical role in postural control and limb coordination. However, limited research exists exploring the interaction between contact sport participation and altered cervical sensorimotor function, as well as an associated increase in musculoskeletal injury risk. CONCLUSIONS: Limited evidence exists linking cervical injury and/or observed deficits in cervical sensorimotor and neuromotor function to musculoskeletal injury risk. Longitudinal studies combining imaging measures (e.g., MRI, DEXA), cervical functional test, and prospective injury risk are needed to further explore the correlation between resultant cervical sensorimotor deficits following contact sport impacts and future musculoskeletal injury risk.

Drill Intensity and Head Impact Exposure in Adolescent Football.

BACKGROUND AND OBJECTIVES: The objective of this study was to examine head-impact exposure by intensity level and position group, and to test the hypothesis that there would be an increase in cumulative head-impact exposure between drill intensities after controlling for duration in each level with air recording the lowest frequency and magnitude and live recording the highest: air < bags < control < thud < live. METHODS: We conducted a prospective, multisite study in 1 season with players from 3 high school football teams (n = 74). Each player wore a sensor-installed mouthguard, which monitored head-impact frequency, peak linear acceleration (PLA), and peak rotational acceleration (PRA). Practice drills and games were categorized by level of contact. RESULTS: A total of 7312 impacts were recorded with a median of 67 (interquartile range:128) impacts per player. After controlling for duration, increases in head-impact outcomes by level of contact were observed (air < bags = control < thud = live). Live drills had higher cumulative head-impact frequency (45.4 ± 53.0 hits) and magnitude (PLA: 766.3 ± 932.9 g; PRA: 48.9 ± 61.3 kilorad/s2) per player than other levels (P < .0001). In comparison, air drills had the lowest cumulative frequency (4.2 ± 6.9 hits) and magnitude (PLA: 68.0 ± 121.6 g; PRA: 6.4 ± 13.2 kilorad/s2). CONCLUSIONS: These data support the levels-of-contact system as a practical approach to limiting head-impact exposure in tackle football. Our findings are clinically important, because data have begun to suggest the relationship between chronic head-impact exposure and decline in brain health. Since head-impact exposure was influenced by levels of contact, regulation of the duration of certain drill intensities (eg, thud, live) may associate with reduced head-impact exposure in high school football.

Prevalence of Acute Neck Pain Following Sports-Related Concussion in High School Athletes.

OBJECTIVES: To explore the prevalence of acute neck pain in high school athletes following sports-related concussion (SRC) and to examine the role of acute neck pain in modifying or amplifying concurrent concussive symptoms. DESIGN: Retrospective observational. SETTING: High school sporting events. PARTICIPANTS: High school athletes who suffered a sports-related concussion between the 2011 and 2019 academic years academic years from the National Athletic Treatment, Injury and Outcomes Network (NATION) Study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of neck pain (yes/no) along with 33 other commonly reported concussion symptoms, number of symptoms reported, mechanism of injury (contact with person/surface or object), sport type (contact/noncontact), and injury history (first time/repeated injury). RESULTS: One hundred thirty-eight of 401 athletes (33.9%) indicated acute neck pain following SRC. Those with neck pain reported significantly more symptoms overall (M = 13.53, SD = 6.89) relative to their non-neck pain counterparts (M = 8.46, SD = 5.68; t [191.35] = 7.11, P < 0.001). Athletes with SRC due to contact with a surface were significantly less likely to report neck pain than those reported contact with a person. Neck pain, repeated injury, and female sex were significantly associated with a greater number of concussion symptoms in the acute phase. CONCLUSIONS: Our data suggest that acute neck pain is a frequent acute symptom following SRC and signals the necessity for additional screening to seek and identify comorbid cervical pathology. Prospective studies should seek to access the benefit of cervical therapy in the early stages in SRC patients with neck pain to reduce the risk of persistent postconcussion symptoms.

The citizen preferences-positive externality trade-off: A survey study of COVID-19 vaccine deployment in Japan.

Objective: Medicine is a scarce resource and a public good that benefits others by bettering patients' health. COVID-19 vaccines in shortage are, 1) a scarce resource and 2) a public good with the positive externality of building herd immunity. These features are expected to drive citizens' attitudes in opposite directions, exclusionist and inclusionist, respectively. Scarcity would drive citizens' exclusionism, while the positive externality might mitigate exclusionism. Setting and design: We recruited 15,000 Japanese adults and asked them to rank, in the context of a COVID-19 vaccine shortage, the deservingness of hypothetical vaccine recipients who differed according to 1) citizenship status, 2) visa type and duration of stay (if foreign), 3) occupation, 4) age, 5) whether they lived with a child, and 6) whether they lived with an elderly individual. Citizenship options were Japanese, Chinese, Taiwanese, South Korean, American, or European. The occupations were healthcare, education, other employed, self-employed, or not employed. The 6 attributes were randomly combined, and respondents were shown 3 hypothetical vaccine recipients: one was Japanese, and the others were foreigners. Treatments: First, through a conjoint design, we created hypothetical vaccine recipients whose attributes were randomized except for the benchmark citizenship, Japanese national. Second, we randomly presented two scenarios for vaccination payments: 1) billed at cost or 2) fully subsidized by the government. Results: 1) Whether the vaccines were billed at cost or fully subsidized did not affect the rankings of deservingness. 2) Japanese citizenship was prioritized. 3) The penalty for being a foreigner was higher for individuals from nations with which Japan has geopolitical tensions. 4) Working in health or education reduced the penalty on foreigners, indicating that the positive externality related to occupation amplifies the positive externality associated with vaccination and mitigates exclusionist attitudes. Conclusions: The positive occupational externalities that amplify the positive externality of vaccination substantially allay the foreigner penalty.