Repetitive Subconcussive Head Impacts Research Articles

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

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

Exposure assessment for repeated sub-concussive head impacts in soccer: The HEalth and Ageing Data IN the Game of football (HEADING) study

The purpose of this paper was to develop exposure estimates for repetitive sub-concussive head impacts (RSHI) for use in epidemiological analyses. We used a questionnaire to collect lifetime history of heading and other head contacts associated with training and playing football from 159 former footballers all members of the English professional football association. We used linear mixed effect regression with player as the random effect, to model the number of headers, blows to the head and head-to-head impacts as a function of potential exposure affecting factors, which were treated as the fixed effects. Exposure affecting factors included playing position, league, context of play (game vs training) and decade of play. Age at time of response to the questionnaire was also included in the models. In model results, playing position was important, with RSHIs being highest among defenders and lowest among goalkeepers. Players headed the ball more during games than in training, and when playing in amateur or youth leagues compared with semi-professional or professional leagues. The average number of reported head impacts declined linearly throughout the observation period (1949–2015). The derived final model for headers explained 43%, 9% and 36% of the between player, within player and total variance in exposure, respectively with good precision and predictive performance. These findings are generally in agreement with previously published results pointing towards the models forming a valid method for estimating exposure to RSHI among former footballers although some further external validation is still warranted.

The effects of subconcussive head impacts on cerebral vascular reactivity

Purpose: One bout of repetitive subconcussive head impacts (SHI) can increase biomarkers of neurological injury, decrease neurovascular coupling, and alter cerebral autoregulation. It is unclear whether a bout of repetitive SHI alters cerebral vascular reactivity to carbon dioxide (CVR). We tested the hypotheses that CVR to hypercapnia (CVRhyper) and hypocapnia (CVRhypo) will decrease after a bout of repetitive SHI in healthy participants. Methods: Eight healthy participants (age: 20±2 y; BMI: 23±3 kg/m2; 2 women) completed four CVR tests: one prior to a bout of SHI (PRE), and three follow-up tests at 2 h, 24 h, and 72 h after the SHI. SHI were induced by 20 soccer headers projected from a soccer JUGS machine (1 header/30 s at 40 km/h and from 12.2 m). Mean arterial pressure (MAP), heart rate (HR), end tidal carbon dioxide tension (PETCO2), middle cerebral artery blood velocity (MCAV) and posterior cerebral artery blood velocity (PCAV) were measured prior to and during each CVR test. MCA conductance (MCAcon) and PCA conductance (PCAcon) were calculated as the quotient of MCAv and PCAv to MAP, respectively. During the CVRhyper test, participants inhaled 6% CO2, 21% O2, 73% N2 gas for 2 min or until PETCO2 was 10 mmHg greater than baseline. 3 min after the CVRhyper test, participants hyperventilated until PETCO2 was 10 mmHg less than baseline for 2 min (CVRhypo). PETCO2 values were plotted against MCAV, PCAV, MCAcon, and PCAcon at baseline and the last 10 s of each CVR test. The slopes of these linear regression lines were calculated for each variable and for both CVR tests. Data are presented as mean±SD. Results: There were no differences from PRE to post SHI for resting HR, PETCO2, MCAV, PCAV, MCAcon, or PCAcon (all p>0.13). A time effect was found for resting MAP (PRE: 90±10; 2 h: 101±8; 24 h: 86±4; 72 h: 88±10 mmHg; p=0.02). There were no differences from PRE to post SHI for the CVRhyper test for MCAV (PRE: 0.10±0.20; 2 h: 0.27±0.17; 24 h: 0.24±0.31; 72 h: 0.24±0.31 cm/s/mmHg; p=0.13), MCAcon (PRE: -0.0009±0.0014; 2 h: -0.0001±0.0023; 24 h: -0.0002±0.0017; 72 h: -0.0011±0.0017 cm/s/mmHg/mmHg; p=0.36), PCAV (PRE: 0.02±0.13; 2 h: 0.07±0.07; 24 h: 0.12±0.18; 72 h: 0.14±0.13 cm/s/mmHg; p=0.26), or PCAcon (PRE: 0.0018±0.0011; 2 h: 0.0014±0.0007; 24 h: 0.0033±0.0033; 72 h: 0.0012±0.0007 cm/s/mmHg/mmHg; p=0.18). There were also no differences from PRE to post SHI for the CVRhypo test for MCAV (PRE: 0.10±0.20; 2 h: 0.27±0.17; 24 h: 0.24±0.31; 72 h: 0.24±0.31 cm/s/mmHg; p=0.13), MCAcon (PRE: 0.0006±0.0019; 2 h: 0.0019±0.0011; 24 h: 0.004±0.0049; 72 h: 0.0025±0.0016 cm/s/mmHg/mmHg; p=0.10), PCAV (PRE: 0.02±0.13; 2 h: 0.07±0.07; 24 h: 0.12±0.18; 72 h: 0.14±0.13 cm/s/mmHg; p=0.26), or PCAcon (PRE: 0.0018±0.0016; 2 h: 0.0019±0.0007; 24 h: 0.004±0.0033; 72 h: 0.0037±0.0014; p=0.09). Conclusion: These preliminary data indicate that a bout of soccer headings does not change CVR to carbon dioxide in the MCA or PCA in healthy adults. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effects of an Acute Bout of Subconcussive Head Impacts on Sympathetic Reactivity

Symptomatic concussed athletes (tested within ~7 d of injury) exhibit an attenuated rise in blood pressure and heart rate during the cold pressor test (CPT), which is indicative of sympathetic hyporeactivity. However, resting blood pressure is elevated following a sports season that has a high incidence of repetitive subconcussive head impacts (SHI) which suggests autonomic or vascular dysfunction. A single session of experimentally induced repetitive SHI increases circulating biomarkers of neuronal injury. In this context, it is unknown if a session of repetitive SHI alters autonomic function.PURPOSEWe tested the hypothesis that the sympathetically‐mediated rise in heart rate and blood pressure during the CPT would be attenuated following a session of repetitive SHI in healthy young adults.METHODSTen healthy participants (age: 20±2 y; 6 females) with ≥3 years of soccer heading experience completed three separate study visits. The CPT (left hand submerged up to the wrist in agitated 0°C water for 120 s) was conducted before soccer heading (0h) and at 2 h (2h), 24 h (24h), and 72 h (72h) after soccer heading. 20 SHI were completed using a soccer heading protocol (ball projected at ~11.2 m/s from 12.2 m every 30 s). Heart rate (HR; 5‐lead electrocardiogram) and beat‐to‐beat blood pressure (MAP; finger photoplethysmography) were continuously recorded at 1 kHz. Mean HR and MAP were extracted during the final minute of the CPT baseline (BL) and every 30 s throughout the CPT. We used mixed‐effects ANOVAs to compare the change (∆) from BL between and within experimental visits. Values are reported as ∆ BL (mean ± SD).RESULTSThere were no differences across timepoints at BL for HR (0h: 58±9 vs. 2h: 60±7, 24h: 59±8, 72h: 62±9 bpm; P=0.19) or MAP (0h: 98±15 vs. 2h: 99±9, 24h: 89±8, 72h: 95±8 mmHg; P=0.09). There was a main effect of time post SHI for ∆ HR (P<0.01) but multiple comparisons did not reveal where differences occurred between 0h (8±6 bpm) vs. 2h (9±7 bpm; P>0.99), 24h (10±7 bpm; P=0.19), and 72h (8±6 bpm; P<0.99). The mean ∆MAP throughout the CPT was lower at 0h (17±13 mmHg) vs. 2h (21±15 mmHg; P<0.01), 24h (23±17 mmHg; P<0.01), and 72h (20±16 mmHg; P<0.01). The ∆MAP during the CPT was lower at 60 s of 0h vs. 24h (24±12 vs. 31±13 mmHg; P<0.01), at 90 s of 0h vs, all post‐SHI (0h: 28±14 vs. 2h: 34±12, 24h: 38±12, 72h: 33±13 mmHg; P<0.01), and at 120 s of 0h vs. all post‐SHI (0h: 27±15 vs. 2h: 33±12, 24h: 37±10, 72h: 34±13 mmHg; P<0.01).CONCLUSIONContrary to our hypothesis, these preliminary data indicate that a single session of repetitive SHI does not attenuate sympathetically‐mediated cardiovascular responses to the CPT. The increase in HR was similar before and after soccer heading; however, the increase in MAP was exacerbated during the CPT at all post‐SHI time points. Thus, there appears to be sympathetic hyperreactivity following a single session of repetitive SHI. This sympathetic hyperreactivity might explain the increase in blood pressure following a sports season associated with a high incidence of repetitive SHI.

A Preclinical Rodent Model for Repetitive Subconcussive Head Impact Exposure in Contact Sport Athletes.

Repetitive subconcussive head impact exposure has been associated with clinical and MRI changes in some non-concussed contact sport athletes over the course of a season. However, analysis of human tolerance for repeated head impacts is complicated by concussion and head impact exposure history, genetics, and other personal factors. Therefore, the objective of the current study was to develop a rodent model for repetitive subconcussive head impact exposure that can be used to understand injury mechanisms and tolerance in the human. This study incorporated the Medical College of Wisconsin Rotational Injury Model to expose rats to multiple low-level head accelerations per day over a 4-week period. The peak magnitude of head accelerations were scaled from our prior human studies of contact sport athletes and the number of exposures per day were based on the median (moderate exposure) and 95th percentile (high exposure) number of exposures per day across the human sample. Following the exposure protocol, rats were assessed for cognitive deficits, emotional changes, blood serum levels of axonal injury biomarkers, and histopathological evidence of injury. High exposure rats demonstrated cognitive deficits and evidence of anxiety-like behaviors relative to shams. Moderate exposure rats did not demonstrate either of those behaviors. Similarly, high exposure rats had histopathological evidence of gliosis [i.e., elevated Iba1 intensity and glial fibrillary acidic protein (GFAP) volume relative to shams] in the basolateral amygdala and other areas. Blood serum levels of neurofilament light (NFL) demonstrated a dose response relationship with increasing numbers of low-level head acceleration exposures with a higher week-to-week rate of NFL increase for the high exposure group compared to the moderate exposure group. These findings demonstrate a cumulative effect of repeated low-level head accelerations and provide a model that can be used in future studies to better understand mechanisms and tolerance for brain injury resulting from repeated low-level head accelerations, with scalable biomechanics between the rat and human.

P.185 Impact-detecting helmets as indicators of concussion and blood brain barrier integrity in university football players

Background: Repetitive sub-concussive head impacts have been associated with changes in brain architecture and neurological symptoms. In this study, we examined the association between repetitive sub-concussive impacts, impact burden, and blood brain barrier (BBB) integrity in university football players. Methods: 59 university football players were followed over the 2019 season. Athletes with diagnosed concussion and those sustaining impacts that alerted a sideline impact monitor (relayed by ferroelectric helmet sensors) underwent dynamic contrast-enhanced MRI (DCE-MRI) within one week of injury/alert, and 4 weeks following initial incident. Results: Helmets recorded 2648 impacts over 48 cumulative hours. 8 concussions occurred during the 2019 season (2.82 per 1000 activity hours). On average, athletes with a diagnosed concussion had 55.3 impacts to the front sensor, compared to 14.1 in non-concussed athletes. Athletes who consented to DCE-MRI (n=5) had 10.78% BBB-D within a week of concussion/alert, and 6.77% BBB-D at 4-weeks. Conclusions: We show quantification of BBB integrity relative to head impact burden for the first time. This preliminary study highlights the potential of impact-detecting helmets to provide relevant impact characteristics and offers a foundation for future work on neurological consequences of repetitive sub-concussive impacts.

Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model.

Posttraumatic headache is one of the most common, debilitating, and difficult symptoms to manage after a traumatic head injury. The development of novel therapeutic approaches is nevertheless hampered by the paucity of preclinical models and poor understanding of the mechanisms underlying posttraumatic headache. To address these shortcomings, we previously characterized the development of posttraumatic headache-like pain behaviors in rats subjected to a single mild closed head injury using a 250 g weight drop. Here, we conducted a follow-up study to further extend the preclinical research toolbox for studying posttraumatic headache by exploring the development of headache-like pain behaviors in male rats subjected to a single, but more severe head trauma (450 g) as well as following repetitive, subconcussive head impacts (150 g). In addition, we tested whether these behaviors involve peripheral calcitonin gene-related peptide signaling by testing the effect of systemic treatment with an anti-calcitonin gene-related peptide monoclonal antibody (anti-calcitonin gene-related peptide mAb). Adult male Sprague Dawley rats (total n = 138) were subjected to diffuse closed head injury using a weight-drop device, or a sham procedure. Three injury paradigms were employed: A single hit, using 450 g or 150 g weight drop, and three successive 150 g weight drop events conducted 72 hours apart. Changes in open field activity and development of cephalic and extracephalic tactile pain hypersensitivity were assessed up to 42 days post head trauma. Systemic administration of the anti-calcitonin gene-related peptide mAb or its control IgG (30 mg/kg) began immediately after the 450 g injury or the third 150 g weight drop with additional doses given every 6 days subsequently. Rats subjected to 450 g closed head injury displayed an acute decrease in rearing and increased thigmotaxis, together with cephalic tactile pain hypersensitivity that resolved by 6 weeks post-injury. Injured animals also displayed delayed and prolonged extracephalic tactile pain hypersensitivity that remained present at 6 weeks post-injury. Repetitive subconcussive head impacts using the 150 g weight drop, but not a single event, led to decreased vertical rearing as well as cephalic and extracephalic tactile pain hypersensitivity that resolved by 6 weeks post-injury. Early and prolonged anti-calcitonin gene-related peptide mAb treatment inhibited the development of the cephalic tactile pain hypersensitivity in both the severe and repetitive subconcussive head impact models. Severe head injury gives rise to a prolonged state of cephalic and extracephalic tactile pain hypersensitivity. These pain behaviors also develop following repetitive, subconcussive head impacts. Extended cephalic tactile pain hypersensitivity following severe and repetitive mild closed head injury are ameliorated by early and prolonged anti-calcitonin gene-related peptide mAb treatment, suggesting a mechanism linked to calcitonin gene-related peptide signaling, potentially of trigeminal origin.

Repetitive Subconcussive Head Impact and Neuro-ophthalmology

Repetitive Subconcussive Head Impact and Neuro-ophthalmology

Neuro-Ophthalmologic Response to Repetitive Subconcussive Head Impacts

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. 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. 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. Ten soccer-ball headings or kicks. 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. 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. 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. ClinicalTrials.gov Identifier: NCT03488381.

Understanding the Consequences of Repetitive Subconcussive Head Impacts in Sport: Brain Changes and Dampened Motor Control Are Seen After Boxing Practice.

ObjectivesThe potential effects of exposure to repetitive subconcussive head impacts through routine participation in sport are not understood. To investigate the effects of repetitive subconcussive head impacts we studied boxers following customary training (sparring) using transcranial magnetic stimulation (TMS), decomposition electromyographic (EMG) and tests of memory.MethodsTwenty amateur boxers performed three 3-min sparring bouts. Parameters of brain function and motor control were assessed prior to sparring and again immediately, 1 h and 24 h post-sparring. Twenty control participants were assessed following mock-sparring.ResultsOne hour after sparring boxers showed increased corticomotor inhibition, altered motor unit recruitment strategies, and decreased memory performance relative to controls, with values returning to baseline by the 24 h follow up.ConclusionRepetitive subconcussive head impacts associated with sparring resulted in acute and transient brain changes similar to those previously reported in soccer heading, providing convergent evidence that sport-related head impacts produce a GABAergic response. These acute changes in brain health are reminiscent of effects seen following brain injury, and suggest a potential mechanism underlying the damaging long-term effects of routine repetitive head impacts in sport.

A common neural signature of brain injury in concussion and subconcussion.

The midbrain is biomechanically susceptible to force loading from repetitive subconcussive head impacts (RSHI), is a site of tauopathy in chronic traumatic encephalopathy (CTE), and regulates functions (e.g., eye movements) often disrupted in concussion. In a prospective longitudinal design, we demonstrate there are reductions in midbrain white matter integrity due to a single season of collegiate football, and that the amount of reduction in midbrain white matter integrity is related to the amount of rotational acceleration to which players' brains are exposed. We then replicate the observation of reduced midbrain white matter integrity in a retrospective cohort of individuals with frank concussion, and further show that variance in white matter integrity is correlated with levels of serum-based tau, a marker of blood-brain barrier disruption. These findings mean that noninvasive structural MRI of the midbrain is a succinct index of both clinically silent white matter injury as well as frank concussion.

Greater exposure to repetitive subconcussive head impacts is associated with vestibular dysfunction and balance impairments during walking

Exposure to repetitive subconcussive head impacts (RSHI), specifically soccer heading, is associated with white matter microstructural changes and cognitive performance impairments. However, the effect of soccer heading exposure on vestibular processing and balance control during walking has not been studied. Galvanic vestibular stimulation (GVS) is a tool that can be used to probe the vestibular system during standing and walking. The purpose of this study was to investigate the association of soccer heading with subclinical balance deficits during walking. Twenty adult amateur soccer players (10 males and 10 females, 22.3 ± 4.5 years, 170.5 ± 9.8 cm, 70.0 ± 10.5 kg) walked along a foam walkway with the eyes closed under 2 conditions: with GVS (∼40 trials) and without GVS (∼40 trials). Outcome measures included mediolateral center-of-mass (COM), center-of-pressure (COP) separation, foot placement, mediolateral ankle modulation, hip adduction, and ankle push off. For each balance mechanism, a GVS response was calculated (GVS, mean [without GVS]). In addition, participants completed a questionnaire, reporting soccer heading exposure over the past year. A linear regression model was used to determine if vestibular processing and balance during walking were related to RSHI exposure. Both foot placement (R2 = 0.324, p = 0.009) and hip adduction (R2 = 0.183, p = 0.50) were predicted by RSHI; whereby, greater exposure to RSHI was associated with greater foot placement and hip adduction responses. However, COM-COP separation (R2 &lt; 0.001, p = 0.927), ankle modulation (R2 = 0.037, p = 0.417), and push off (R2 &lt; 0.001, p = 0.968) were not related to RSHI exposure. Individuals who were exposed to greater RSHI were more perturbed by vestibular stimulation during walking, suggesting that there may be vestibular dysfunction and balance impairments with frequent heading; specifically, individuals with greater exposure to RSHI responded with larger foot placement and hip adduction responses to GVS.

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 (β = 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.

Single Season Changes in Resting State Network Power and the Connectivity between Regions: Distinguish Head Impact Exposure Level in High School and Youth Football Players.

The effect of repetitive sub-concussive head impact exposure in contact sports like American football on brain health is poorly understood, especially in the understudied populations of youth and high school players. These players, aged 9-18 years old may be particularly susceptible to impact exposure as their brains are undergoing rapid maturation. This study helps fill the void by quantifying the association between head impact exposure and functional connectivity, an important aspect of brain health measurable via resting-state fMRI (rs-fMRI). The contributions of this paper are three fold. First, the data from two separate studies (youth and high school) are combined to form a high-powered analysis with 60 players. These players experience head acceleration within overlapping impact exposure making their combination particularly appropriate. Second, multiple features are extracted from rs-fMRI and tested for their association with impact exposure. One type of feature is the power spectral density decomposition of intrinsic, spatially distributed networks extracted via independent components analysis (ICA). Another feature type is the functional connectivity between brain regions known often associated with mild traumatic brain injury (mTBI). Third, multiple supervised machine learning algorithms are evaluated for their stability and predictive accuracy in a low bias, nested cross-validation modeling framework. Each classifier predicts whether a player sustained low or high levels of head impact exposure. The nested cross validation reveals similarly high classification performance across the feature types, and the Support Vector, Extremely randomized trees, and Gradboost classifiers achieve F1-score up to 75%.

Sex differences in white matter alterations following repetitive subconcussive head impacts in collegiate ice hockey players.

ObjectiveRepetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI.MethodsTwenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT).ResultsSignificant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores.ConclusionsThe results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes.

Head impact exposure from match participation in women’s rugby league over one season of domestic competition

ObjectivesTo quantify the magnitude, frequency, duration and distribution of head impact exposure in a women’s rugby league competition. DesignProspective cohort study. MethodsTwenty-one players had a wireless impact measuring device (X2Biosystems XPatch) behind their right ear during match participation. Head impact data were collected and downloaded for analysis. Median peak linear and rotational accelerations and impact locations between player positions were assessed using a Friedman repeated measures ANOVA on ranks with a Wilcoxon signed-rank test for post hoc analysis with a Bonferroni correction. ResultsA total of 1659 impacts to the head >10g were recorded (range 10g–91g) over the nine competition matches. There was a mean of 184±18 impacts per-match resulting in a mean of 14±12 impacts per-player per-match. The No. 8 prop recorded a mean of 29±27 impacts per-match, the No. 12 second-row forward recorded the highest median peak resultant linear acceleration (16g) per-match and the No. 11 second-row forward recorded the highest median peak resultant rotational acceleration (3696rad/s2). ConclusionsOur cohort of 21 female rugby league athletes were exposed to repetitive sub-concussive head impact exposure with an average of 14 impacts per-player per-match. Forwards were exposed to more impacts per-match than backs and these impacts were of higher magnitude. Most impacts occurred on the side of the head and were sustained during the second half of the game. Clinicians, coaches and players should be aware of the rates and magnitude of head impacts in female rugby league athletes.

The Effect of Repeated Soccer Ball Heading on Cortico-spinal Excitability and Inhibition

Postural control has been shown to decline following a bout of soccer ball heading, although mechanisms underling this impairment remain unclear. Repetitive sub-concussive head impacts (RSHI) may disrupt cortico-spinal pathways to trigger these changes, however, no data exists.

Cortical thinning in former professional soccer players.

Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

Altered Neurochemistry in Former Professional Soccer Players without a History of Concussion.

Soccer is played by more than 250 million people worldwide. Repeatedly heading the ball may place soccer players at high risk for repetitive subconcussive head impacts (RSHI). This study evaluates the long-term effects of RSHI on neurochemistry in athletes without a history of clinically diagnosed concussion, but with a high exposure to RSHI. Eleven former professional soccer players (mean age 52.0±6.8 years) and a comparison cohort of 14 age- and gender-matched, former non-contact sport athletes (mean age 46.9±7.9 years) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation. In the soccer players a significant increase was observed in both choline (Cho), a membrane marker, and myo-inositol (ml), a marker of glial activation, compared with control athletes. Additionally, ml and glutathione (GSH) were significantly correlated with lifetime estimate of RSHI within the soccer group. There was no significant difference in neurocognitive tests between groups. Results of this study suggest an association between RSHI in soccer players and MRS markers of neuroinflammation, suggesting that even subconcussive head impacts affect the neurochemistry of the brain and may precede neurocognitive changes. Future studies will need to determine the role of neuroinflammation in RSHI and the effect on neurocognitive function.