'Knock down the brain': a nonlinear analysis of electroencephalography to study the effects of sub-concussion in boxers.

BACKGROUND AND PURPOSE: Boxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub-concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data. METHODS: Twenty-one boxers were selected (mean ± SD, age 28.38 ± 5.5 years; weight 67.55 ± 8.90 kg; years of activity 6.76 ± 5.45; education 14.19 ± 3.08 years) and divided into 'beginner' and 'advanced' groups. The Montreal Cognitive Assessment and the Frontal Assessment Battery were administered; EEG data were collected in both eyes-open (EO) and eyes-closed (EC) conditions during resting states. Analyses of EEG data included normalized power spectral density (nPSD), power law exponent (PLE), detrended fluctuation analysis and multiscale entropy. Statistical analyses were used to compare the groups. RESULTS: Significant differences in nPSD and PLE were observed between the beginner and advanced boxers, with advanced boxers showing decreased mean nPSD and PLE (nPSD 4-7 Hz, p = 0.013; 8-13 Hz, p = 0.003; PLE frontal lobe F3 EC, p = 0.010). Multiscale entropy analysis indicated increased entropy at lower frequencies and decreased entropy at higher frequencies in advanced boxers (F3 EC, p = 0.024; occipital lobe O1 EO, p = 0.029; occipital lobe O2 EO, p = 0.036). These changes are similar to those seen in Alzheimer's disease. CONCLUSION: Nonlinear analysis of EEG data shows potential as a neurophysiological biomarker for detecting the asymptomatic phase of chronic traumatic encephalopathy in boxers. This methodology could help monitor athletes' health and reduce the risk of future neurological injuries in sports.

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.

Titrating the Translational Relevance of a Low-Level Repetitive Head Impact Model.

Recently, there has been increased attention in the scientific community to the phenomenon of sub-concussive impacts, those hits to the head that do not cause the signs and symptoms of a concussion. Some authors suggest that sub-concussive impacts may alter behavior and cognition, if sustained repetitively, but the mechanisms underlying these changes are not well-defined. Here, we adapt our well-established weight drop model of repetitive mild traumatic brain injury (rmTBI) to attempt to produce a model of low-level repetitive head impacts (RHI). The model was modified to eliminate differences in latency to right following impact and gross behavioral changes after a single cluster of hits. Further, we varied our model in terms of repetition of impact over a 4-h span to mimic the repeated sub-concussive impacts that may be experienced by an athlete within a single day of play. To understand the effects of a single cluster of RHIs, as well as the effect of an increased impact frequency within the cluster, we evaluated classical behavioral measures, serum biomarkers, cortical protein quantification, and immunohistochemistry both acutely and sub-acutely following the impacts. In the absence of gross behavioral changes, the impact protocol did generate pathology, in a dose-dependent fashion, in the brain. Evaluation of serum biomarkers revealed limited changes in GFAP and NF-L, which suggests that their diagnostic utility may not emerge until the exposure to low-level head impacts reaches a certain threshold. Robust decreases in both IL-1ß and IL-6 were observed in the serum and the cortex, indicating downregulation of inflammatory pathways. These experiments yield initial data on pathology and biomarkers in a mouse model of low-level RHIs, with relevance to sports settings, providing a starting point for further exploration of the potential role of anti-inflammatory processes in low-level RHI outcomes, and how these markers may evolve with repeated exposure.

Repeated Sub-Concussive Impacts and the Negative Effects of Contact Sports on Cognition and Brain Integrity.

Sports are yielding a wealth of benefits for cardiovascular fitness, for psychological resilience, and for cognition. The amount of practice, and the type of practiced sports, are of importance to obtain these benefits and avoid any side effects. This is especially important in the context of contact sports. Contact sports are not only known to be a major source of injuries of the musculoskeletal apparatus, they are also significantly related to concussion and sub-concussion. Sub-concussive head impacts accumulate throughout the active sports career, and thus can cause measurable deficits and changes to brain health. Emerging research in the area of cumulative sub-concussions in contact sports has revealed several associated markers of brain injury. For example, recent studies discovered that repeated headers in soccer not only cause measurable signs of cognitive impairment but are also related to a prolonged cortical silent period in transcranial magnetic stimulation measurements. Other cognitive and neuroimaging biomarkers are also pointing to adverse effects of heading. A range of fluid biomarkers completes the picture of cumulating effects of sub-concussive impacts. Those accumulating effects can cause significant cognitive impairment later in life of active contact sportswomen and men. The aim of this review is to highlight the current scientific evidence on the effects of repeated sub-concussive head impacts on contact sports athletes' brains, identify the areas in need of further investigation, highlight the potential of advanced neuroscientific methods, and comment on the steps governing bodies have made to address this issue. We conclude that there are indeed neural and biofluid markers that can help better understand the effects of repeated sub-concussive head impacts and that some aspects of contact sports should be redefined, especially in situations where sub-concussive impacts and concussions can be minimized.

The effects of repetitive head impacts on postural control: A systematic review.

OBJECTIVES: The purpose of our study was to investigate the association between repetitive head impact (RHI) exposure and postural control. DESIGN: Systematic review. METHODS: PubMed, Embase and PsycInfo were searched using a self-developed search term including the keywords balance OR postural control AND repetitive OR sub-concussive head impacts. Twenty-one studies excluding non-peer reviewed studies, secondary studies, cross-sectional studies, animal studies, and studies investigating concussion were included for further analyses. We rated Level of Evidence and quality using the Centre for Evidence-Based Medicine tool, the Quality Assessment for the Systematic Review of Effectiveness, and the Sub-concussion Specific Tool. RESULTS: All included studies were grouped into Category I and II studies. Category I included trials investigating the effects of controlled soccer heading on postural control (n=8) and Category II studies were cohort studies investigating on-the-field changes between preseason and postseason assessments on postural control measures (n=13). Findings were heterogeneous, with a tendency towards no effects of RHI on clinical postural control measures. Most laboratory studies in Category I used instrumented assessments whereas on-the-field studies in Category II used both instrumented and non-instrumented assessments. CONCLUSIONS: Due to heterogeneous findings, future studies aiming to investigate the effects of RHI on different athlete populations are needed on other participant cohorts. Furthermore, the combination of objective clinical balance measures may be a promising approach to accurately measure how, and to what degree, postural control may be affected by RHI.

An Evaluation of Omega-3 Status and Intake in Canadian Elite Rugby 7s Players.

BACKGROUND: EPA and DHA n-3 FA play crucial roles in both neurological and cardiovascular health and high dietary intakes along with supplementation suggest potential neuroprotection and concussion recovery support. Rugby athletes have a high risk of repetitive sub-concussive head impacts which may lead to long-term neurological deficits, but there is a lack of research looking into n-3 FA status in rugby players. We examined the dietary n-3 FA intake through a FFQ and n-3 FA status by measuring the percentage of n-3 FA and O3I in elite Canadian Rugby 7s players to show distribution across O3I risk zones; high risk, <4%; intermediate risk, 4 to 8%; and low risk, >8%. METHODS: n-3 FA profile and dietary intake as per FFQ were collected at the beginning of the 2017-2018 Rugby 7s season in male (n = 19; 24.84 ± 2.32 years; 95.23 ± 6.93 kg) and female (n = 15; 23.45 ± 3.10 years; 71.21 ± 5.79 kg) athletes. RESULTS: O3I averaged 4.54% ± 1.77, with female athlete scores slightly higher, and higher O3I scores in supplemented athletes (4.82% vs. 3.94%, p = 0.183), with a greater proportion of non-supplemented athletes in the high-risk category (45.5% vs. 39.1%). Dietary intake in non-supplemented athletes did not meet daily dietary recommendations for ALA or EPA + DHA compared to supplemented athletes. CONCLUSIONS: Overall, despite supplementation, O3I score remained in the high-risk category in a proportion of athletes who met recommended n-3 FA dietary intakes, and non-supplemented athletes had a higher proportion of O3I scores in the high-risk category, suggesting that dietary intake alone may not be enough and athletes may require additional dietary and n-3 FA supplementation to reduce neurological and cardiovascular risk.

The Effect of Sub-Concussive Impacts during a Rugby Tackling Drill on Brain Function.

Concussion is known to detrimentally affect brain health. Rugby tackles commonly occur with high collision force between tackler and ball carrier, and low impact head contact is not uncommon. Cognitive deficits following a bout of soccer ball heading has been attributed to the impact and termed sub-concussion. Although soccer ball heading studies provide evidence for acute effects of sub-concussion, it is unknown whether this phenomenon occurs following rugby tackles. This study investigates the acute effects of rugby tackles on brain function and balance in rugby players. Twenty-six volunteers were assigned to either the ball carrier (9), tackler (9) or control (8) group. Controls performed running without the tackle. Outcome measures included corticomotor function using transcranial magnetic brain stimulation (TMS) and balance was assessed by a series of tasks performed on a NeuroCom Balance Master before and immediately after a tackle training drill. Following the tackling bout, the cortical silent period (cSP) increased for the tacklers with no change for ball carrier and control groups, and no differences between groups for balance measures were observed. Lengthening of cSP observed in the tacklers following the bout has been reported in studies of concussion and may indicate long term detrimental effects.

Repeated Long-Term Sub-concussion Impacts Induce Motor Dysfunction in Rats: A Potential Rodent Model.

Whilst detrimental effects of repeated sub-concussive impacts on neurophysiological and behavioral function are increasingly reported, the underlying mechanisms are largely unknown. Here, we report that repeated sub-concussion with a light weight drop (25 g) in wild-type PVG rats for 2 weeks does not induce detectable neuromotor dysfunction assessed by beamwalk and rotarod tests. However, after 12 weeks of repeated sub-concussion, the rats exhibited moderate neuromotor dysfunction. This is the first study to demonstrate development of neuromotor dysfunction following multiple long-term sub-concussive impacts in rats. The outcomes may offer significant opportunity for future studies to understand the mechanisms of sub-concussion-induced neuropsychological changes.

Brain Metabolite Levels in Sedentary Women and Non-contact Athletes Differ From Contact Athletes.

White matter tracts are known to be susceptible to injury following concussion. The objective of this study was to determine whether contact play in sport could alter white matter metabolite levels in female varsity athletes independent of changes induced by long-term exercise. Metabolite levels were measured by single voxel proton magnetic resonance spectroscopy (MRS) in the prefrontal white matter at the beginning (In-Season) and end (Off-Season) of season in contact (N = 54, rugby players) and non-contact (N = 23, swimmers and rowers) varsity athletes. Sedentary women (N = 23) were scanned once, at a time equivalent to the Off-Season time point. Metabolite levels in non-contact athletes did not change over a season of play, or differ from age matched sedentary women except that non-contact athletes had a slightly lower myo-inositol level. The contact athletes had lower levels of myo-inositol and glutamate, and higher levels of glutamine compared to both sedentary women and non-contact athletes. Lower levels of myo-inositol in non-contact athletes compared to sedentary women indicates long-term exercise may alter glial cell profiles in these athletes. The metabolite differences observed between contact and non-contact athletes suggest that non-contact athletes should not be used as controls in studies of concussion in high-impact sports because repetitive impacts from physical contact can alter white matter metabolite level profiles. It is imperative to use athletes engaged in the same contact sport as controls to ensure a matched metabolite profile at baseline.

Effects of sub-concussion on neuropsychological performance and its potential mechanisms: A narrative review.

Concussion and mild traumatic brain injury (mTBI) are recognised as serious medical events that are relatively common in contact sports. Recently, the seemingly non-injurious phenomenon of sub-concussion has gained interest among neuroscience researchers and early studies are showing that there may be some acute and chronic effects on brain health and function with repeated sub-concussive events of the type seen in soccer, where players strike the ball with the head, and collision sports like the rugby codes. The aim of this narrative review is to describe sub-concussion and the current understanding of short and long term effects of repeated minor impacts that have been found to occur in human and animal models. Here, potential mechanisms for cognitive dysfunction following sub-concussion and recommend directions for future research are discussed. The Potential mechanisms of injuries resulting from sub-concussion such as changes in blood brain barrier integrity, neuroinflammation, cognitive impairment, and oxidative stress damage, among other changes in central nervous system function vary considerably making understanding of the underlying causative mechanism challenging for researchers. Some evidence suggests a link between impaired cerebrovascular function and cognitive impairment which poses a potential mechanism linking the two. It is hoped that this review helps guide researchers toward a potential direction of investigations.

Serum Protein Biomarker Findings Reflective of Oxidative Stress and Vascular Abnormalities in Male, but Not Female, Collision Sport Athletes.

Studies have indicated that concussive and sub-concussive brain injuries that are frequent during collision sports may lead to long-term neurological abnormalities, however there is a knowledge gap on how biological sex modifies outcomes. Blood-based biomarkers can help to identify the molecular pathology induced by brain injuries and to better understand how biological sex affects the molecular changes. We therefore analyzed serum protein biomarkers in male (n = 50) and female (n = 33) amateur Australian rules footballers (i.e., Australia's most participated collision sport), both with a history of concussion (HoC) and without a history of concussion (NoHoC). These profiles were compared to those of age-matched control male (n = 24) and female (n = 20) athletes with no history of neurotrauma or participation in collision sports. Serum levels of protein markers indicative of neuronal, axonal and glial injury (UCH-L1, NfL, tau, p-tau, GFAP, BLBP, PEA15), metabolic (4-HNE) and vascular changes (VEGF-A, vWF, CLDN5), and inflammation (HMGB1) were assessed using reverse phase protein microarrays. Male, but not female, footballers had increased serum levels of VEGF-A compared to controls regardless of concussion history. In addition, only male footballers who had HoC had increased serum levels of 4-HNE. These findings being restricted to males may be related to shorter collision sport career lengths for females compared to males. In summary, these findings show that male Australian rules footballers have elevated levels of serum biomarkers indicative of vascular abnormalities (VEGF-A) and oxidative stress (4-HNE) in comparison to non-collision control athletes. While future studies are required to determine how these findings relate to neurological function, serum levels of VEGF-A and 4-HNE may be useful to monitor subclinical neurological injury in males participating in collision sports.

The independent influence of concussive and sub-concussive impacts on soccer players' neurophysiological and neuropsychological function.

Accumulating research demonstrates that repetitive sub-concussive impacts can alter the structure, function and connectivity of the brain. However, the functional significance of these alterations as well as the independent contribution of concussive and sub-concussive impacts to neurophysiological and neuropsychological health are unclear. Accordingly, we compared the neurophysiological and neuropsychological function of contact athletes with (concussion group) and without (sub-concussion group) a history of concussion, to non-contact athletes. We evaluated event-related brain potentials (ERPs) elicited during an oddball task and performance on a targeted battery of neuropsychological tasks. Athletes in the sub-concussion and concussion groups exhibited similar amplitude reductions in the ERP indices of attentional resource allocation (P3b) and attentional orienting (P3a) relative to non-contact athletes. However, only athletes in the concussion group exhibited reduced amplitude in the ERP index of perceptual attention (N1). Athletes in the sub-concussion and concussion groups also exhibited deficits in memory recall relative to non-contact athletes, but athletes in the concussion group also exhibited significantly more recall errors than athletes in the sub-concussion group. Additionally, only athletes in the concussion group exhibited response delays during the oddball task. The current findings suggest that sub-concussive impacts are associated with alterations in the neurophysiological and neuropsychological indices of essential cognitive functions, albeit to a lesser degree than the combination of sub-concussive and concussive impacts.

A Season of American Football Is Not Associated with Changes in Plasma Tau.

American football athletes are routinely exposed to sub-concussive impacts over the course of the season. This study sought to examine the effect of a season of American football on plasma tau, a potential marker of axonal damage. Nineteen National Collegiate Athletic Association (NCAA) football athletes underwent serial blood sampling over the course of the 2014-2015 season at those times in which the number and magnitude of head impacts likely changed. Non-contact sport controls (NCAA men's swim athletes; n = 19) provided a single plasma sample for comparison. No significant differences were observed between control swim athletes and football athletes following a period of non-contact (p = 0.569) or a period of contact (p = 0.076). Football athletes categorized as starters (n = 11) had higher tau concentrations than non-starters (n = 8) following a period of non-contact (p = 0.039) and contact (p = 0.036), but not higher than swimmers (p = 1.000 and p = 1.000, respectively). No difference was noted over the course of the season in football athletes, irrespective of starter status. Despite routine head impacts common to the sport of American football, no changes were observed over the course of the season in football athletes, irrespective of starter status. Further, no difference was observed between football athletes and non-contact control swim athletes following a period of non-contact or contact. These data suggest that plasma tau is not sensitive enough to detect damage associated with repetitive sub-concussive impacts sustained by collegiate-level football athletes.

Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading.

INTRODUCTION: There is growing concern around the effects of concussion and sub-concussive impacts in sport. Routine game-play in soccer involves intentional and repeated head impacts through ball heading. Although heading is frequently cited as a risk to brain health, little data exist regarding the consequences of this activity. This study aims to assess the immediate outcomes of routine football heading using direct and sensitive measures of brain function. METHODS: Nineteen amateur football players (5 females; age 22±3y) headed machine-projected soccer balls at standardized speeds, modelling routine soccer practice. The primary outcome measure of corticomotor inhibition measured using transcranial magnetic stimulation, was assessed prior to heading and repeated immediately, 24h, 48h and 2weeks post-heading. Secondary outcome measures were cortical excitability, postural control, and cognitive function. RESULTS: Immediately following heading an increase in corticomotor inhibition was detected; further to these electrophysiological alterations, measurable reduction memory function were also found. These acute changes appear transient, with values normalizing 24h post-heading. DISCUSSION: Sub-concussive head impacts routine in soccer heading are associated with immediate, measurable electrophysiological and cognitive impairments. Although these changes in brain function were transient, these effects may signal direct consequences of routine soccer heading on (long-term) brain health which requires further study.