The Relations Among Childhood Maltreatment and Later Intimate Partner Violence Victimization With and Without a Weapon in a Sample of Pregnant Black Individuals.

Black pregnant and postpartum individuals are at risk for intimate partner violence (IPV), and those with a history of childhood maltreatment and IPV are even more likely to be re-victimized during pregnancy. However, it is unknown if specific types of child maltreatment predict later IPV with and without a weapon better than others. The current study sought to (i) document the prevalence of childhood maltreatment and IPV and (ii) examine the relations among types of childhood maltreatment and later IPV with and without a weapon within a sample of Black individuals seeking prenatal care at a large public hospital in the southeastern United States. Participants (n = 186; mean age = 27.2 years, SD = 5.3) completed measures assessing childhood maltreatment and IPV with and without a weapon. Approximately 68.5% of participants (n = 124) endorsed experiencing childhood maltreatment, while 42.6% (n = 78) endorsed experiencing IPV. The bivariate relations among five childhood maltreatment types (i.e., sexual, physical, and emotional abuse, physical and emotional neglect) and IPV with and without a weapon were assessed. All childhood maltreatment subtype scores-except childhood physical neglect-were significantly higher among participants who reported a history of IPV with or without a weapon compared to participants who denied a history of IPV with or without a weapon. Logistic regression models revealed childhood sexual abuse emerged as the only significant predictor of experiencing IPV with a weapon (B = 0.10, p = .003) and IPV without a weapon (B = 0.11, p = .001). For every point increase in childhood sexual abuse subtype score, the odds of experiencing IPV with and without a weapon increased by 10% (OR = 1.10, 95%CI [1.04, 1.18]) and 12% (OR = 1.12, [1.05, 1.20]), respectively. Findings suggest that screening for childhood sexual abuse may provide a critical opportunity for maternity care providers to identify individuals at increased risk for IPV victimization with and without a weapon.

Association between perimenopausal age and greater posttraumatic stress disorder and depression symptoms in trauma-exposed women.

OBJECTIVE: This study aimed to determine the relationship between stages of the menopause transition (premenopausal, perimenopausal, and postmenopausal) on symptoms of posttraumatic stress disorder (PTSD) and depression in trauma-exposed women. METHODS: A cross-sectional study conducted between 2005 and 2017 recruited and enrolled an urban community sample (n = 6,093) from nonpsychiatric medical clinic waiting rooms of Grady Memorial Hospital, a public safety net hospital in Atlanta, Georgia. Participants were female, 18 to 65 years old, and predominantly Black/African American. RESULTS: Of the 6,093 participants, 93.8% were Black/African American, 2.5% were White, and 3.8% were of all other races (Hispanic/Latino, Asian, multiracial). Participants younger than 40 years were categorized as premenopausal (n = 3,166), between 40 and 55 years of age were categorized as perimenopausal (n = 2,127), and older than 55 years were categorized as postmenopausal (n = 790). Menopause status was associated with total PTSD symptom severity ( F2,5416 = 9.61, P < 0.001), symptom severity within all three PTSD symptom clusters (avoidance/numbing symptoms: F2,5416 = 7.10, P < 0.001; intrusive symptoms: F2,5416 = 7.04, P < 0.001; hyperarousal symptoms: F2,5409 = 8.31, P < 0.001), and depression symptom severity ( F2,5148 = 11.4, P < 0.001). Compared with both premenopausal and postmenopausal women, perimenopausal women reported significantly worse total PTSD symptoms, symptoms in the hyperarousal cluster, and depressive symptoms. CONCLUSIONS: The current cross-sectional data show that symptoms of PTSD and depression in women are associated with reproductive age, such that perimenopausal women show higher symptom severity than premenopausal and postmenopausal women. Future longitudinal studies can reveal how changes in hormones over the course of the menopause transition impact the symptoms, neurobiology, and psychophysiology of PTSD.

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.

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.

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.

Frequent and Recent Non-fatal Strangulation/Choking During Sex and Its Association With fMRI Activation During Working Memory Tasks.

Being strangled, or "choked," by a sexual partner has emerged as a prevalent, often wanted and consensual sexual behavior among adolescent and young adult women, yet the neurological consequences of repeated exposure to this behavior are unknown. The objective of the study was to examine the association between a history of repeated, recent choking/strangling episodes during sex and fMRI activation during working memory tasks in young adult women. This case-control study involved young adult women (18-30 years old) at a large, public university, and consisted of two study groups: a choking group consisting of participants who were recently and frequently choked/strangled during sex by a partner (≥4 times in the past 30 days) and a choking-naïve (control) group who had never been choked/strangled during sex. Participants completed two variations of the N-back (0-back, 1-back, and 2-back) working memory task during functional magnetic resonance imaging (fMRI): verbal and visual N-back tasks. Data from 20 participants per group were available for analysis. Between-group differences for accuracy and reaction time were not significant for either variation of the N-back task. Significant differences in fMRI activation patterns were detected between the choking and the choking-naïve groups for the three contrasts of interest (1-back > 0-back, 2-back > 0-back, and 2-back > 1-back). The choking group exhibited increased activation in multiple clusters relative to the choking-naïve group for the contrasts between the 1-back and 2-back conditions compared to the 0-back conditions (e.g., superior frontal gyrus, corpus callosum). However, the choking-naïve group exhibited increased activation relative to the choking group in several clusters for the 2-back > 1 back contrast (e.g., splenium, middle frontal gyrus). These data indicate that recent, frequent exposure to partnered sexual strangulation is associated with different neural activation patterns during verbal and visual working memory tasks compared to controls, suggesting that being choked/strangled during sex may modify the allocation of neural resources at increasing levels of cognitive load. Further investigation into the neurologic effects of this sexual behavior is warranted, given the prevalence of sexual choking among adolescent and young adult women.

The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury.

HUIBREGTSE, M.E, Bazarian, J.J., Shultz, S.R., and Kawata K. The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury. NEUROSCI BIOBEHAV REV XX (130) 433-447, 2021.- Blood biomarkers can serve as objective measures to gauge traumatic brain injury (TBI) severity, identify patients at risk for adverse outcomes, and predict recovery duration, yet the clinical use of blood biomarkers for TBI is limited to a select few and only to rule out the need for CT scanning. The biomarkers often examined in neurotrauma research are proteomic markers, which can reflect a range of pathological processes such as cellular damage, astrogliosis, or neuroinflammation. However, proteomic blood biomarkers are vulnerable to degradation, resulting in short half-lives. Emerging biomarkers for TBI may reflect the complex genetic and neurometabolic alterations that occur following TBI that are not captured by proteomics, are less vulnerable to degradation, and are comprised of microRNA, extracellular vesicles, and neurometabolites. Therefore, this review aims to summarize our understanding of how biomarkers for brain injury escape the brain parenchymal space and appear in the bloodstream, update recent research findings in several proteomic biomarkers, and characterize biological significance and examine clinical utility of microRNA, extracellular vesicles, and neurometabolites.

Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study.

While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.

Does acute soccer heading cause an increase in plasma S100B? A randomized controlled trial.

The purpose of this study was to test the effect of subconcussive head impacts on acute changes in plasma S100B. In this randomized controlled trial, 79 healthy adult soccer players were randomly assigned to either the heading (n = 41) or kicking-control groups (n = 38). The heading group executed 10 headers with soccer balls projected at a speed of 25 mph, whereas the kicking-control group performed 10 kicks. Plasma samples were obtained at pre-, 0h post-, 2h post- and 24h post-intervention and measured for S100B. The primary hypothesis was that there would be a significant group difference (group-by-time interaction) in plasma S100B at 2h post-intervention. Secondary hypotheses included (1) no significant group differences in plasma S100B concentrations at 0h post- and 24h post-intervention; (2) a significant within-group increase in S100B concentrations in the heading group at 2h post-intervention compared to pre-intervention; and (3) no significant within-group changes in plasma S100B in the kicking-control group. Data from 68 subjects were available for analysis (heading n = 37, kicking n = 31). There were no differences in S100B concentrations between heading and kicking groups over time, as evidenced by nonsignificant group-by-time interaction at 2h post-intervention (B = 2.20, 95%CI [-22.22, 26.63], p = 0.86) and at all the other time points (0h post: B = -11.05, 95%CI [-35.37, 13.28], p = 0.38; 24h post: B = 16.11, 95%CI [-8.29, 40.51], p = 0.20). Part of the secondary outcome, the heading group showed elevation in plasma S100B concentrations at 24h post-intervention compared to pre-heading baseline (B = 19.57, 95%CI [3.13, 36.02], p = 0.02), whereas all other within-group comparisons in both remained nonsignificant. The data suggest that 10 bouts of acute controlled soccer headings do not elevate S100B concentrations up to 24-hour post-heading. Further dose-response studies with longer follow-up time points may help determine thresholds of acute soccer heading exposure that are related to astrocyte activation. The protocol was registered under ClinicalTrials.gov (NCT03488381; retrospectively registered.).

Acute Time-Course Changes in CCL11, CCL2, and IL-10 Levels After Controlled Subconcussive Head Impacts: A Pilot Randomized Clinical Trial.

OBJECTIVE: To examine changes in plasma levels of CCL11, CCL2, and IL-10 after 10 controlled soccer headers. SETTING: Laboratory setting. PARTICIPANTS: Thirty-nine healthy soccer players with at least 3 years of soccer heading experience, between 18 and 26 years old, and enrolled at a large public university. DESIGN: In this randomized clinical trial using a soccer heading model, participants were randomized into the heading (n = 22) or kicking-control (n = 17) groups to perform 10 headers or kicks. MAIN MEASURES: Plasma levels of CCL11, CCL2, and IL-10 at preintervention and 0, 2, and 24 hours postintervention. RESULTS: Mixed-effects regression models did not reveal any significant group differences in changes of plasma CCL11, CCL2, or IL-10 levels from preintervention. Within the heading group, there was a statistically significant time by years of heading experience interaction with 2.0-pg/mL increase in plasma CCL11 each year of prior experience at 24 hours postintervention (P = .001). CONCLUSION: Findings from this study suggest that 10 soccer headers do not provoke an acute inflammatory response. However, the acute CCL11 response may be influenced by prior exposure to soccer headers, providing a precedent for future field studies that prospectively track head impact exposure and changes in CCL11.

Neuro-Ophthalmologic Response to Repetitive Subconcussive Head Impacts: A Randomized Clinical Trial.

Importance: Subconcussive head impacts have emerged as a complex public health concern. The oculomotor system is sensitive to brain trauma; however, neuro-ophthalmologic response to subconcussive head impacts remains unclear. Objective: To examine whether subconcussive head impacts cause impairments in neuro-ophthalmologic function as measured by the King-Devick test (KDT) and oculomotor function as measured by the near point of convergence. Design, Setting, and Participants: In this randomized clinical trial, adult soccer players were randomized into either a heading group or kicking (control) group. The heading group executed 10 headers with soccer balls projected at a speed of 25 mph. The kicking-control group followed the same protocol but with 10 kicks. Peak linear and rotational head accelerations were assessed with a triaxial accelerometer. The KDT speed and error and near point of convergence were assessed at baseline (preheading or prekicking) and at 0, 2, and 24 hours after heading or kicking. Exposures: Ten soccer-ball headings or kicks. Main Outcomes and Measures: The primary outcome was the group-by-time interaction of KDT speed at 0 hours after heading or kicking. The secondary outcomes included KDT speed at 2 hours and 24 hours after heading or kicking, KDT error, and near point of convergence. Results: A total of 78 individuals enrolled (heading group, n = 40; kicking-control group, n = 38). Eleven individuals (heading group: 4 women; mean [SD] age, 22.5 [1.0] years; kicking-control group, 3 women and 4 men; mean [SD] age, 20.9 [1.1] years) voluntarily withdrew from the study. Data from 67 participants with a mean (SD) age of 20.6 (1.7) years were eligible for analysis (heading, n = 36; kicking-control, n = 31). Mean (SD) peak linear accelerations and peak rotational accelerations per impact for the heading group were 33.2 (6.8) g and 3.6 (1.4) krad/s2, respectively. Conversely, soccer kicking did not induce a detectable level of head acceleration. Both groups showed improvements in KDT speed (heading group: 0 hours, -1.2 [95% CI, -2.2 to -0.1] seconds; P = .03; 2 hours, -1.3 [95% CI, -2.6 to 0] seconds; P = .05; 24 hours, -3.2 [95% CI, -4.3 to -2.2] seconds; P < .001; kicking-control group: 0 hours, -3.3 [95% CI, -4.1 to -2.5] seconds; P < .001; 2 hours, -4.1 [95% CI, -5.1 to -3.1] seconds; P < .001; 24 hours, -5.2 [95% CI, -6.2 to -4.2] seconds; P < .001). Group differences occurred at all postintervention points; the kicking-control group performed KDT faster at 0 hours (-2.2 [95% CI, -0.8 to -3.5] seconds; P = .001), 2 hours (-2.8 [95% CI, -1.2 to -4.4] seconds; P < .001), and 24 hours after the intervention (-2.0 [95% CI, -0.5 to -3.4] seconds; P = .007) compared with those of the heading group. Conclusions and Relevance: These data support the hypothesis that neuro-ophthalmologic function is affected, at least in the short term, by subconcussive head impacts that may affect some individuals in some contact sports. Further studies may help determine if these measures can be a useful clinical tool in detecting acute subconcussive injury. Trial Registration: ClinicalTrials.gov Identifier: NCT03488381.

Association between Muscle Damage and Head Impacts in High School American Football.

Subconcussive head impacts (SHI), defined as impacts to the cranium that do not result in concussion symptoms, are gaining traction as a major public health concern. The contribution of physiological factors such as physical exertion and muscle damage to SHI-dependent changes in neurological measures remains unknown. A prospective longitudinal study examined the association between physiological factors and SHI kinematics in 15 high school American football players over one season. Players wore a sensor-installed mouthguard for all practices and games, recording frequency and magnitude of all head impacts. Serum samples were collected at 12 time points (pre-season, pre- and post-game for five in-season games, and post-season) and were assessed for an isoenzyme of creatine kinase (CK-MM) primarily found in skeletal muscle. Physical exertion was estimated in the form of excess post-exercise oxygen consumption (EPOC) from heart rate data captured during the five games. Mixed-effect regression models indicated that head impact kinematics were significantly and positively associated with change in CK-MM but not EPOC. There was a significant and positive association between CK-MM and EPOC. These data suggest that when examining SHI, effects of skeletal muscle damage should be considered when using outcome measures that may have an interaction with muscle damage.

Preliminary evidence-based recommendations for return to learn: a novel pilot study tracking concussed college students.

AIM: Students re-entering the academic setting after a concussion is commonly referred to as return-to-learn and, to date, very few studies have examined the return-to-learn aspect of concussion recovery. METHODOLOGY: Nine college-aged, full-time students who were diagnosed with concussions were monitored throughout their concussion recovery. The severity for five chief symptoms (headache, dizziness, difficulty concentrating, fatigue, anxiety) were recorded six-times per day through text messages, and daily phone calls recorded participant's behavioral traits. RESULTS: We identified five behavioral variables which significantly influenced symptom resolution (music, sleep, physical activity, water and time) (p = 0.0004 to p = 0.036). Additionally, subjects reported math and computer-oriented courses as the most difficult (33 and 44%, respectively). CONCLUSION: We introduce a novel approach to monitor concussed students throughout their recovery, as well as factors that may influence concussion recovery process.

In Vivo Protocol of Controlled Subconcussive Head Impacts for the Validation of Field Study Data.

Subconcussive hits pose a threat to neuronal health as they have shown to induce neuronal structural damage and functional impairment without causing outward symptomology and appear to be a key contributor to an irreversible neurodegenerative disease, chronic traumatic encephalopathy (CTE). In addition, athletes can incur more than 1,000 of these hits per season. The subconcussive soccer heading model (SSHM) is a relevant, reproducible, and leading method of isolating and examining the effects of these subconcussive head impacts. By controlling variables such as ball traveling speed, the frequency of impacts, interval, ball placement to the head, as well as by measuring head impact magnitude, the SSHM provides the scientific community with a superior avenue of investigating the acute subconcussive effects on neuronal health. In this paper, we demonstrate the utility of SSHM in studying a time-course expression of neurofilament-light polypeptide (NF-L) in plasma in a repeated measures fashion. NF-L is an axonal injury marker that has previously been shown to be elevated in boxers and football players following subconcussive head trauma. Thirty-four adult aged soccer players were recruited and randomly assigned to either a soccer heading (n = 18) or kicking (n = 16) group. The heading group executed 10 headers with soccer balls projected at a velocity of 25 mph over 10 min. The kicking group followed the same protocol with 10 kicks. Plasma samples were obtained before and at 0 h, 2 h, and 24 h after heading/kicking and assessed for NF-L expressions. The heading group showed a gradual increase in plasma NF-L expression and peaked at 24 h after the heading protocol, whereas the kicking group remained consistent across the time points. These results confirmed the NF-L data from clinical field studies, encouraging the use of SSHM to validate clinical subconcussion data.

Association of Increased Serum S100B Levels With High School Football Subconcussive Head Impacts.

Astrocyte-enriched marker, S100B, shows promise for gauging the severity of acute brain trauma, and understanding subconcussive effects will advance its utility in tracking real-time acute brain damage. The aim of the study was to investigate whether serum S100B elevations were associated with frequency and magnitude of subconcussive head impacts in adolescents. This prospective cohort study of 17 high-school football players consisted of the following 12 time points: pre-season baseline, 5 in-season pre-post games, and post-season. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA) and peak rotational (PRA) head accelerations from every practice and game. During the 5 games, players wore chest-strap heart-rate monitors to estimate players' excess post-exercise oxygen consumption (EPOC), accounting for physical exertion effects. At each time point, blood samples were obtained and assessed for S100B and creatine kinase levels to account for astrocyte damage/activation and muscle damage, respectively. Using k-means clustering on the impact data, players were categorized into high- or low-impact group. Two players withdrew during the first month of the study. A total of 156 blood samples from 15 players were assessed for S100B and creatine kinase levels and included in the analysis. A median value of 596 head impacts from 15 players were recorded during all practices and games in a season. S100B levels were significantly elevated in all post-game measures compared with the respective pre-game values (median-increase, 0.022 µg/L; interquartile-range, 0.011-0.043 µg/L, p < 0.05 for all games). Greater acute S100B increases were significantly associated with greater impact frequency, sum of PLA and PRA, with negligible contributions from physical exertion and muscle damage effects. The high-impact group exhibited greater increases in serum S100B levels at post-games than the low-impact group (high vs. low, 0.043 ± 0.035 µg/L vs. 0.019 ± 0.017 µg/L, p = 0.002). The degree of acute S100B increases was correlated with subconcussive head impact exposure, suggesting that acute astrocyte damage may be induced in an impact-dependent manner. Acute changes in serum S100B levels may become a useful tool in monitoring real-time brain damage in sports.

Association of Acute Increase in Plasma Neurofilament Light with Repetitive Subconcussive Head Impacts: A Pilot Randomized Control Trial.

The purpose of the study was to examine an association of repetitive subconcussive head impacts with changes in plasma neurofilament light (NF-L) levels following 10 bouts of controlled soccer heading. In this randomized control trial, 37 healthy adult soccer players were randomly assigned into either a heading (n = 19) or kicking-control group (n = 18). The heading group executed 10 headers with soccer balls projected at a velocity of 25 mph over 10 min. Plasma samples were obtained at pre-heading baseline, 0 h, 2 h, and 24 h post-heading. The kicking-control group followed the same protocol with 10 kicks. Plasma NF-L was measured using ultrasensitive single-molecule array technology. Data from 34 subjects were eligible for analysis (heading n = 18 and kicking n = 16). Ten subconcussive head impacts induced a gradual increase in plasma NF-L expression for the heading group (ß = 0.0297, standard error [SE] = 0.01, p = 0.0049), whereas there was no significant time effect for the kicking-control group. A follow-up analysis revealed that a significant difference appeared at 24 h post-heading (3.68 ± 0.30 pg/mL) compared with pre-heading (3.12 ± 0.29 pg/mL, p = 0.0013; Cohen's d = 1.898). At the 24 h post-heading time-point, the plasma NF-L level for the heading group was significantly higher than that of the kicking-control group with an estimated mean difference of 0.66 pg/mL (SE = 0.22, p = 0.0025). The data suggest that the increased level of plasma NF-L was driven by repetitive subconcussive head impacts and required longer than 2 h after the head impacts for the increase to be detected. Plasma NF-L levels may serve as an objective marker to monitor acute axonal burden from subconcussive head impacts.

Oculomotor Response to Cumulative Subconcussive Head Impacts in US High School Football Players: A Pilot Longitudinal Study.

Importance: Repetitive subconcussive head impacts in sports have emerged as a complex public health issue. Most of these head impacts remain asymptomatic yet have the potential to cause insidious neurological deficit if sustained repetitively. Near point of convergence (NPC) values have shown to reflect subclinical neuronal damage; however, the longitudinal pattern of NPC changes in association with subconcussive head impacts remains unclear. Objectives: To examine the NPC response to recurring subconcussive head impacts in a single high school football season through a series of repeated measurements. Design, Setting, and Participants: This prospective case-series study of US varsity high school football players included baseline measurements of NPC, measurements at pregame and postgame points from 6 in-season games, and postseason follow-up measurements (a total of 14 points). An accelerometer-embedded mouthguard measured head impact frequency and magnitude from all practices and games. During the 6 games, players wore chest-strap heart rate monitors to record heart rate and estimate their excess postexercise oxygen consumption, accounting for possible physical exertion effects on NPC values. Exposures: Players participated in practices and games with no restriction. Main Outcomes and Measures: Near point of convergence. Results: The 12 included players were all boys, with a mean (SD) age of 16.4 (0.5) years. A total of 8009 head impacts, 177 907 g of peak linear acceleration, and 16 123 371 rad/s2 of peak rotational acceleration were recorded from the players in a single football season. There was a significant increase in NPC over time until the middle of the season (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 3, 6.42 [1.93] cm; P = .01), which was significantly associated with subconcussive head impact frequency and magnitude (0.02 cm per 100 g of peak linear acceleration [SE, 0.0108; 95% CI, 0.0436-0.004]; P = .01; 0.023 cm per 10 000 rad/s2 of peak rotational acceleration [SE, 0.009; 95% CI, 0.041-0.0105]; P = .02). However, NPC values began to normalize toward baseline level from midseason (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 6, 5.75 [2.23] cm; P = .32), as supported by a significant quadratic trend (ß [SE], -0.002 [0.001] cm/d; P = .003), while participants continued to incur subconcussive head impacts. Conclusions and Relevance: This longitudinal case series study suggests that NPC can be perturbed over the long term by subconcussive head impacts but may normalize over time. The oculomotor system may have an adaptational capacity to subclinical head impacts, yet the mechanism for such remains an open question and warrants further investigation.

Improving the translational potential of rodent models to study the behavioral and pathophysiological effects of repetitive mild traumatic brain injury.

Chronic traumatic encephalopathy (CTE) is thought to be caused by repetitive head impacts. Consequently, there is a need to develop rodent models to better understand the behavioral and pathophysiological changes of repetitive mild traumatic brain injury (rmTBI) and to determine the link between rmTBI and CTE. This Neuro Forum article reviews recent rodent rmTBI models, comparing the impact methods and outcome measures in terms of translational potential.