Amnesia after Repeated Head Impact Is Caused by Impaired Synaptic Plasticity in the Memory Engram.

Subconcussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency head impact (HFHI) causes chronic cognitive deficits in mice through synaptic changes. To better understand the mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic mice to enable visualization and manipulation of memory engrams. We labeled the fear memory engram in male and female mice exposed to an aversive experience and subjected them to sham or HFHI. Upon subsequent exposure to natural memory recall cues, sham, but not HFHI, mice successfully retrieved fearful memories. In sham mice the hippocampal engram neurons exhibited synaptic plasticity, evident in amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, and increased dendritic spine volume compared with nonengram neurons. In contrast, although HFHI mice retained a comparable number of hippocampal engram neurons, these neurons did not undergo synaptic plasticity. This lack of plasticity coincided with impaired activation of the engram network, leading to retrograde amnesia in HFHI mice. We validated that the memory deficits induced by HFHI stem from synaptic plasticity impairments by artificially activating the engram using optogenetics and found that stimulated memory recall was identical in both sham and HFHI mice. Our work shows that chronic cognitive impairment after HFHI is a result of deficiencies in synaptic plasticity instead of a loss in neuronal infrastructure, and we can reinstate a forgotten memory in the amnestic brain by stimulating the memory engram. Targeting synaptic plasticity may have therapeutic potential for treating memory impairments caused by repeated head impacts.

Brain morphometry in former American football players: findings from the DIAGNOSE CTE research project.

Exposure to repetitive head impacts in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE), which currently can be diagnosed only at post-mortem. American football players are at higher risk of developing CTE given their exposure to repetitive head impacts. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at post-mortem in living individuals using structural MRI. MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 54, age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each traumatic encephalopathy syndrome (TES) diagnosis, core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, insula, temporal pole and superior frontal gyrus. Post hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus, amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe Age × Group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggested that MRI morphometrics detect abnormalities in individuals with a history of repetitive head impact exposure that resemble the anatomic distribution of pathological findings from post-mortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggested that brain morphometry must be complemented by other types of measures to characterize individuals with repetitive head impacts.

Characterizing the Effects of Concussion and Head Impact Exposure: Design, Methods, and Participant Traits of the CARE 2.0 Study.

OBJECTIVE: This article describes the design, methods, and participant characteristics of the second phase of the Concussion Assessment, Research, and Education (CARE) Consortium study ("CARE 2.0") of the effects of concussion and repetitive head impact exposure on neuropsychiatric health. METHODS: The authors conducted a prospective multisite observational study of male and female collegiate athletes and military service academy cadets and midshipmen participating in the CARE study. Participants were assessed at three time points: undergraduate baseline (UB), before departure from university or service academy (exit), and up to 6 years following graduation (postgrad) via an online battery of brain health assessments. Participant characteristics were compared across the three time points and four levels of head impact exposure. RESULTS: A total of 4,643 participants completed the exit assessment, and 3,981 completed the postgrad assessment. Relative to the UB assessment cohort, the exit and postgrad assessment cohorts differed with respect to the percentage of women, baseline Wechsler Test of Adult Reading scores, National Collegiate Athletic Association division category, sport contact level, and number of previous concussions. The median standardized difference across balancing variables, assessment time points, and degree of head impact exposure was 0.12 (with 90% of effect sizes ≤0.29). CONCLUSIONS: Although there were some statistically significant differences between participants across assessments, the effect sizes were modest, and overall the data suggest that the exit and postgrad cohorts reflect the characteristics of the baseline cohort. The CARE study design and its large, richly characterized sample provide an opportunity to answer important questions about cumulative and persistent effects of concussion and repetitive head impact exposure on neuropsychiatric health.

Lost in translation: the association of international status and native language on concussion in collegiate athletes in the United States.

OBJECTIVE: The purpose of this study was to characterize the associations of international student status and native language on time (in days) with the date of injury to (i) diagnosis, (ii) symptom resolution, and (iii) return to sport. METHODS: Utilizing data from a cross-sectional cohort of 1,044 concussion cases from LIMBIC MATARS member institutions (n = 11) in the US, we conducted two, matched case-control designs. Cases were divided into two groups: (i) international (n = 32) or domestic students (n = 32) and (ii) English as an Additional Language (EAL) speakers (n = 18) or Native English language speakers (n = 18). Both groups were individually matched to their respective controls based on gender, age, sport, and preexisting health conditions. RESULTS: There were no significant differences in days from injury to diagnosis (p = 0.94), symptom resolution (p = 0.64), or return to sport (p = 0.15) between international and domestic athletes. EAL speakers experienced symptom resolution approximately 7.5 days sooner (Md = 4.50; IQR = 4.00, 8.00) than Native English language speakers (Md = 12.00; IQR = 7.00, 21.00, p = 0.01). CONCLUSIONS: Our findings suggest that native language is associated with symptom resolution in collegiate athletes. Healthcare professionals should consider barriers related to native language that may impact symptom reporting and the overall injury experience of diverse collegiate athletes.

The effect of safety modifications on head kinematics experienced during common skills in women's artistic gymnastics.

The objective of this study was to evaluate the effect of skill modifications on head motion experienced during women's artistic gymnastics skills. Nine gymnasts (four beginner and five advanced) completed three trials of up to 24 skill progressions, each consisting of a skill and two progressive safety modifications. Gymnasts were instrumented with mouthpiece sensors embedded with an accelerometer and gyroscope collecting motion data at 200, 300, and 500 Hz during each skill performance. Peak-to-peak linear and rotational kinematics during contact phases and peak rotational kinematics during non-contact phases were computed. A mixed-effects model was used to compare differences in modification status nested within skill categories. Timer skills (i.e. drills that simulate performance of a gymnastics skill) resulted in the highest median ΔLA and ΔRA of all skill categories, and 132 skill performances exceeded 10 g ΔLA during a contact phase. Modifications were associated with significant reductions in head kinematics during contact phases of timers, floor skills, bar releases, and vault skills. Gymnasts can be exposed to direct and indirect head accelerations at magnitudes consistent with other youth contact sports, and common safety modifications may be effective at reducing head motion during contact and non-contact phases of gymnastics skills.

Smart Textile Impact Sensor for e-Helmet to Measure Head Injury.

Concussions, a prevalent public health concern in the United States, often result from mild traumatic brain injuries (mTBI), notably in sports such as American football. There is limited exploration of smart-textile-based sensors for measuring the head impacts associated with concussions in sports and recreational activities. In this paper, we describe the development and construction of a smart textile impact sensor (STIS) and validate STIS functionality under high magnitude impacts. This STIS can be inserted into helmet cushioning to determine head impact force. The designed 2 × 2 STIS matrix is composed of a number of material layered structures, with a sensing surface made of semiconducting polymer composite (SPC). The SPC dimension was modified in the design iteration to increase sensor range, responsiveness, and linearity. This was to be applicable in high impact situations. A microcontroller board with a biasing circuit was used to interface the STIS and read the sensor's response. A pendulum test setup was constructed to evaluate various STISs with impact forces. A camera and Tracker software were used to monitor the pendulum swing. The impact forces were calculated by measuring the pendulum bob's velocity and acceleration. The performance of the various STISs was measured in terms of voltage due to impact force, with forces varying from 180 to 722 N. Through data analysis, the threshold impact forces in the linear range were determined. Through an analysis of linear regression, the sensors' sensitivity was assessed. Also, a simplified model was developed to measure the force distribution in the 2 × 2 STIS areas from the measured voltages. The results showed that improving the SPC thickness could obtain improved sensor behavior. However, for impacts that exceeded the threshold, the suggested sensor did not respond by reflecting the actual impact forces, but it gave helpful information about the impact distribution on the sensor regardless of the accurate expected linear response. Results showed that the proposed STIS performs satisfactorily within a range and has the potential to be used in the development of an e-helmet with a large STIS matrix that could cover the whole head within the e-helmet. This work also encourages future research, especially on the structure of the sensor that could withstand impacts which in turn could improve the overall range and performance and would accurately measure the impact in concussion-causing impact ranges.

Pilot Collection and Evaluation of Head Kinematics in Stock Car Racing.

The goal of this work was to collect on-track driver head kinematics using instrumented mouthpieces and characterize environmental exposure to accelerations and vibrations. Six NASCAR drivers were instrumented with custom-fit mouthpieces to collect head kinematic data. Devices were deployed at four tracks during practice and testing environments and configured to collect approximately 11 min of linear acceleration and rotational velocity data at 200 Hz. This continuous data collection, combined with film review, allowed extraction of complete laps of data. In addition to typical data processing methods, a moving-point average was calculated and subtracted from the overall signal for both linear acceleration and rotational velocity to determine the environmental component of head motion. The current analysis focuses on 42 full laps of data collected at four data collection events. The number of laps per track ranged from 2 to 23. Linear acceleration magnitudes for all 42 laps ranged from 2.46 to 7.48 g and rotational velocity ranged from 1.25 to 3.35 rad/s. After subtracting the moving average, linear acceleration ranged from 0.92 to 5.45 g and rotational velocity ranged from 0.57 to 2.05 rad/s. This study has established the feasibility of using an instrumented mouthpiece to measure head kinematics in NASCAR and presented a technique for isolating head motion due to cornering acceleration from those due to short-term perturbations experienced by the driver.

Biomechanical characteristics of concussive and sub-concussive impacts in youth sports athletes: A systematic review and meta-analysis.

This study aimed to quantitatively investigate and report the biomechanical characteristics of concussive and sub-concussive impacts in youth sports. A systematic search was conducted in September 2022 to identify biomechanical impact studies in athletes ≤18 years of age. Twenty-six studies met the inclusion criteria for quantitative synthesis and analysis. DerSimonian Laird random effects model was used to pool data across the included studies. The pooled estimate of mean peak linear and rotational acceleration of concussive impacts in male youth athletes was 85.56 g (95% CI 69.34-101.79) and 4505.58 rad/s2 (95% CI 2870.28-6140.98), respectively. The pooled estimate of mean peak linear and rotational acceleration of sub-concussive impacts in youth athletes was 22.89 g (95% CI 20.69-25.08) and 1290.13 rad/s2 (95% CI 1050.71-1529.55), respectively. A male vs female analysis in sub-concussive impacts revealed higher linear and rotational acceleration in males and females, respectively. This is the first study to report on impact data in both sexes of youth athletes. Disparity in kinematic impact values suggests future research should aim for standardised measures to reduce heterogeneity in data. Despite this, the data reveals notable impact data that youth athletes are exposed to, suggesting modifications may be required to reduce long-term neurological risks.

Characterization of Head Acceleration Exposure During Youth Football Practice Drills.

Many head acceleration events (HAEs) observed in youth football emanate from a practice environment. This study aimed to evaluate HAEs in youth football practice drills using a mouthpiece-based sensor, differentiating between inertial and direct HAEs. Head acceleration data were collected from athletes participating on 2 youth football teams (ages 11-13 y) using an instrumented mouthpiece-based sensor during all practice sessions in a single season. Video was recorded and analyzed to verify and assign HAEs to specific practice drill characteristics, including drill intensity, drill classification, and drill type. HAEs were quantified in terms of HAEs per athlete per minute and peak linear and rotational acceleration and rotational velocity. Mixed-effects models were used to evaluate the differences in kinematics, and generalized linear models were used to assess differences in HAE frequency between drill categories. A total of 3237 HAEs were verified and evaluated from 29 football athletes enrolled in this study. Head kinematics varied significantly between drill categorizations. HAEs collected at higher intensities resulted in significantly greater kinematics than lower-intensity drills. The results of this study add to the growing body of evidence informing evidence-based strategies to reduce head impact exposure and concussion risk in youth football practices.

Characterization of head impact exposure in boys' youth ice hockey.

Ice hockey has one of the highest concussion rates among youth sports. Sensor technology has been implemented in contact and collision sports to inform the frequency and severity of head impacts experienced on-ice. However, existing studies have utilized helmet-mounted sensors with limited accuracy. The objective of this study was to characterize head kinematics of contact events in a sample of youth boys' hockey players using a validated instrumented mouthpiece with improved accuracy. Head kinematics from 892 video-verified events were recorded from 18 athletes across 127 sessions. Median peak resultant linear acceleration, rotational velocity, and rotational acceleration of video-verified events were 7.4 g, 7.7 rad/s, and 576 rad/s2, respectively. Contact events occurred at a higher rate in games (2.48 per game) than practices (1.30 per practice). Scenarios involving head contact had higher peak kinematics than those without head contact. This study improves our understanding of head kinematics in boys' youth hockey.

Differences in head impact biomechanics between playing positions in Canadian high school football players.

The objective of this study was to compare head impact magnitudes and time between impacts among positions in Canadian high-school football. Thirty nine players from two high-school football teams were recruited and assigned a position profile: Profile 1 (quarterback, receiver, defensive back, kicker), Profile 2 (linebacker, running back), and Profile 3 (linemen). Players wore instrumented mouthguards to measure peak magnitudes of linear and angular acceleration and velocity for each head impact throughout the season. A principal component analysis reduced the dimensionality of biomechanical variables, resulting in one principal component (PC1) score assigned to every impact. Time between impacts was calculated by subtracting the timestamps of subsequent head impacts within a session. Significant differences in PC1 scores and time between impacts occurred between playing position profiles (ps<0.001). Post-hoc comparisons determined that PC1 was greatest in Profile 2, followed by Profiles 1 and 3. Time between impacts was lowest in Profile 3, followed by Profiles 2 and 1. This study delivers a new method of reducing the multidimensionality of head impact magnitudes and suggests different Canadian high-school football playing positions experience different head impact magnitudes and frequencies, which is important for monitoring concussion and repetitive head impact exposure.

Quantifying head impacts and neurocognitive performance in collegiate boxers.

Head impacts and neurocognition were quantified in 27 intercollegiate male boxers engaged in two, two-minute sparring rounds. Head impacts were measured using Instrumented Boxing Headgear (IBH). Pre and post-sparring neurocognitive performance was compared using two computerized neuropsychological test batteries (CNTs): Immediate Post-concussion Assessment and Cognitive Testing (ImPACT™) and Automated Neuropsychological Assessment Metrics - Military Battery (ANAM4® MIL). An average of 27.63 ± 17.87 impacts above the 9.6 g IBH threshold were recorded per boxer, with average peak linear acceleration of 23.48 ± 15.20 g and average peak rotational acceleration of 1761.40 ± 1064.34 rad/s2. Small, but measurable declines in delayed memory and improvement in response time from pre- to post-bout were noted. Number of impacts and concussion history predicted degraded memory performance. This is a unique quantification of head impacts in collegiate boxing, which were similar in frequency and location, but lower in magnitude as compared to amateur boxing. Improved understanding of impact kinematics may enhance safety in boxing and other contact sports. Subtle post-bout decrements in delayed memory performance and mild improvement in response time reinforce prior research and provide evidence of congruence in our two CNT assessments, which may facilitate comparisons of outcomes across settings utilizing these tests.

Quantification of Head Acceleration Events in Rugby League: An Instrumented Mouthguard and Video Analysis Pilot Study.

Instrumented mouthguards (iMG) were used to collect head acceleration events (HAE) in men's professional rugby league matches. Peak linear acceleration (PLA), peak angular acceleration (PAA) and peak change in angular velocity (ΔPAV) were collected using custom-fit iMG set with a 5 g single iMG-axis recording threshold. iMG were fitted to ten male Super League players for thirty-one player matches. Video analysis was conducted on HAE to identify the contact event; impacted player; tackle stage and head loading type. A total of 1622 video-verified HAE were recorded. Approximately three-quarters of HAE (75.7%) occurred below 10 g. Most (98.2%) HAE occurred during tackles (59.3% to tackler; 40.7% to ball carrier) and the initial collision stage of the tackle (43.9%). The initial collision stage resulted in significantly greater PAA and ΔPAV than secondary contact and play the ball tackle stages (p < 0.001). Indirect HAE accounted for 29.8% of HAE and resulted in significantly greater ΔPAV (p < 0.001) than direct HAE, but significantly lower PLA (p < 0.001). Almost all HAE were sustained in the tackle, with the majority occurring during the initial collision stage, making it an area of focus for the development of player protection strategies for both ball carriers and tacklers. League-wide and community-level implementation of iMG could enable a greater understanding of head acceleration exposure between playing positions, cohorts, and levels of play.

Head Kinematics in Youth Ice Hockey by Player Speed and Impact Direction.

Hockey is a fast-paced sport known for body checking, or intentional collisions used to separate opponents from the puck. Exposure to these impacts is concerning, as evidence suggests head impact exposure (HIE), even if noninjurious, can cause long-term brain changes. Currently, there is limited understanding of the effect of impact direction and collision speed on HIE. Video analysis was used to determine speed and direction for 162 collisions from 13 youth athletes. These data were paired with head kinematic data collected with an instrumented mouthpiece. Relationships between peak resultant head kinematics and speeds were evaluated with linear regression. Mean athlete speeds and relative velocity between athletes ranged from 2.05 to 2.76 m/s. Mean peak resultant linear acceleration, rotational velocity, and rotational acceleration were 13.1 g, 10.5 rad/s, and 1112 rad/s2, respectively. Significant relationships between speeds and head kinematics emerged when stratified by contact characteristics. HIE also varied by direction of collision; most collisions occurred in the forward-oblique (ie, offset from center) direction; frontal collisions had the greatest magnitude peak kinematics. These findings indicate that HIE in youth hockey is influenced by speed and direction of impact. This study may inform future strategies to reduce the severity of HIE in hockey.

Head impact exposure and concussion in women's collegiate club lacrosse.

This study sought to describe head impact exposure in women's collegiate club lacrosse. Eleven women's collegiate club lacrosse players wore head impact sensors during eight intercollegiate competitions. Video recordings of competitions were used to verify impact data. Athletes completed questionnaires detailing their concussion history and perceived head impact exposure. During the monitored games, no diagnosed concussions were sustained. Three athletes reported sustaining head impacts (median = 0; range: 0-3 impacts per game). Six impacts registered by the sensors were verified on video across a total of 81 athlete-game exposures. Verified impacts had a median peak linear acceleration of 21.0 g (range: 18.3 g - 48.3 g) and peak rotational acceleration of 1.1 krad/s2 (range: 0.7 krad/s2 - 5.7 krad/s2). Women competing in collegiate club lacrosse are at a low risk of sustaining head impacts, comparable to previous reports of the high school and collegiate varsity levels of play.

Changes in resting-state functional brain connectivity associated with head impacts over one men's semi-professional soccer season.

Soccer, as a contact sport, exposes players to repetitive head impacts, especially through heading the ball. The question of a long-term brain cumulative effect remains. Our objective was to determine whether exposure to head impacts over one soccer season was associated with changes in functional brain connectivity at rest, using magnetic resonance imaging (MRI). In this prospective cohort study, 10 semi-professional men soccer players, aged 18-25 years, and 20 age-matched men athletes without a concussion history and who do not practice any contact sport were recruited in Bordeaux (France). Exposure to head impacts per soccer player during competitive games over one season was measured using video analysis. Resting-state functional magnetic resonance imaging data were acquired for both groups at two times, before and after the season. With a seed-based analysis, resting-state networks that have been intimately associated with aspects of cognitive functioning were investigated. The results showed a mean head impacts of 42 (±33) per soccer player over the season, mainly intentional head-to-ball impacts and no concussion. No head impact was found among the other athletes. The number of head impacts between the two MRI acquisitions before and after the season was associated with increased connectivity within the default mode network and the cortico-cerebellar network. In conclusion, our findings suggest that the brain functioning changes over one soccer season in association with exposure to repetitive head impacts.

Neuropsychological Change After a Single Season of Head Impact Exposure in Youth Football.

OBJECTIVES: Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes. METHOD: Over 200 participants (ages 9-13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes. RESULTS: For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (ß) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9-10, 11-13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9-10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001. CONCLUSION: These findings suggest that in the 9-10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.

Video analysis of concussion mechanisms and immediate management in French men's professional football (soccer) from 2015 to 2019.

In this study, the concussion mechanisms were analyzed in male professional competition football, with the main objective to specify the frequency of head-to-head impact, and immediate management of the concussed players was described in order to check its compliance with the recommendations of football's governing bodies. Based on continuously recorded data from the French Football Federation (FFF), a retrospective database of all reported concussions during matches in the 1st and 2nd French Male leagues was generated comprising seasons 2015/16-2018/19. Injury mechanisms, playing action, immediate medical assessment and management of concussed players, and foul play-referee's decision, were analyzed from video recordings. In total, 41 concussions were reported (incidence rate of 0.44/1000 hours of match exposure [95% CI: 0.40 to 0.49]) of which 36 were identified and analyzed on video sequences. The commonest playing action leading to concussion was aerial challenge (61%), and the main mechanism was head-to-head impact (47%). Following the head impact, 28% of concussed players were not medically assessed on pitch and 53% returned to play the same match. Head-to-head impact was not associated with systematic medical assessment, nor with foul play. In conclusion, the main cause of concussions involved head-to-head impact occurring when two players challenge for heading the ball in the air. The detection of potential concussive head impacts and the immediate management of players possibly concussed during matches remain insufficient according to the international recommendations. Some rules changes, with particular vigilance in case of head-to-head impact, should be discussed.

Validity of the 2014 traumatic encephalopathy syndrome criteria for CTE pathology.

INTRODUCTION: Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed. METHODS: A total of 336 consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses. RESULTS: A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 1.2-5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12-0.59). DISCUSSION: TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction.

One season of head-to-ball impact exposure alters functional connectivity in a central autonomic network.

Repetitive head impacts represent a risk factor for neurological impairment in team-sport athletes. In the absence of symptoms, a physiological basis for acute injury has not been elucidated. A basic brain function that is disrupted after mild traumatic brain injury is the regulation of homeostasis, instantiated by activity across a specific set of brain regions that comprise a central autonomic network. We sought to relate head-to-ball impact exposure to changes in functional connectivity in a core set of central autonomic regions and then to determine the relation between changes in brain and changes in behavior, specifically cognitive control. Thirteen collegiate men's soccer players and eleven control athletes (golf, cross-country) underwent resting-state fMRI and behavioral testing before and after the season, and a core group of cortical, subcortical, and brainstem regions was selected to represent the central autonomic network. Head-to-ball impacts were recorded for each soccer player. Cognitive control was assessed using a Dot Probe Expectancy task. We observed that head-to-ball impact exposure was associated with diffuse increases in functional connectivity across a core CAN subnetwork. Increased functional connectivity between the left insula and left medial orbitofrontal cortex was associated with diminished proactive cognitive control after the season in those sustaining the greatest number of head-to-ball impacts. These findings encourage measures of autonomic physiology to monitor brain health in contact and collision sport athletes.