Subconcussions in sport is a growing field of interest and concern as deteriorative effects of these impacts have been shown in athletes without a diagnosed concussion. Detecting subconcussions is extremely difficult and there is no standardized method to recognize these injuries. A first step in identifying subconcussion is taking a closer look at concussions. The vestibular system has been shown to be negatively affected after concussive injuries which can be quantified via oculomotor function and pupillometry. Currently, King Devick (KD) style tests and Pupillary Light Reflex (PLR) are two popular tests that can be administered to athletes to gather clinical eye measures relating to oculomotor function and pupillometry. This study aimed to investigate how clinical eye measures change through serial in-season testing of Division 1 (D1) soccer athletes. Head impacts throughout a soccer season were recorded and we hypothesized that a greater number of head impacts would result in negative clinical changes even in the absence of a diagnosed concussion. No major trends were observed in soccer athletes that can be associated with trends seen in concussed populations. Soccer athletes were found to be slightly more likely to test abnormally than non-contact controls and soccer athletes with a greater number of head impacts were found to have slightly more abnormal tests than athletes with fewer head impacts. Overall, this study provides a dataset of pre and post-season measurements and uniquely includes multiple in-season measurements to provide a new perspective on oculomotor function and pupillary light reflex over the course of a sports season. / Master of Science / Subconcussions in sport is a growing field of interest and concern as deteriorative effects of these impacts have been shown in athletes without a diagnosed concussion. Detecting subconcussions is extremely difficult and there is no standardized method to recognize these injuries. The first step at identifying subconcussions is to more closely look at concussions. Eye movements and pupil response to stimuli can be affected after a concussive injury. Currently, King Devick (KD) style tests and Pupillary Light Reflex (PLR) are two popular tests that can be administered to athletes to gather clinical eye measures relating to eye motion and pupil response to stimuli. This study aimed to investigate how clinical eye measures change through repeated in-season testing of Division 1 (D1) soccer athletes. Head impacts throughout a soccer season were recorded and we hypothesized that a greater number of head impacts would result in negative clinical changes even in the absence of a diagnosed concussion. No major trends were observed in soccer athletes that can be associated with trends seen in concussed populations. Soccer athletes were found to be slightly more likely to test abnormally than non-contact controls and soccer athletes with a greater number of head impacts were found to have slightly more abnormal tests than athletes with fewer head impacts. Overall, this study provides a dataset of pre and post-season measurements and uniquely includes multiple in-season measurements to provide a new perspective on clinical eye measures over the course of a sports season.

In this prospective longitudinal investigation of Division-I collegiate football players, the acute and longer-term effects of repetitive subconcussive impacts on plasma S100β and PINCH levels and concussion-related symptom score were examined. The first aim was to investigate the acute repetitive subconcussive impact effect by comparing the biomarker levels at pre and post full-gear practice, followed by examining the relationship of head impact magnitude and frequency of on acute increases in S100β and PINCH levels and symptom score. Hypotheses for the first aim were that there would be acute increases in plasma S100β and PINCH levels, but no change would be observed in symptom score. A significant relationship between subconcussive impact kinematics and acute changes in outcome measurements would be observed only in S100β. The second aim was to examine the longer-term effect of subconcussive effects on plasma S100β and PINCH levels as well as symptom score compared to the pre-season baseline. It was hypothesized that the players who sustained high frequency and magnitude of subconcussive impact would induce chronically high levels of plasma PINCH compared to the baseline. However, chronic effect would not be found in plasma S100β and symptom score. Independent variables were time (pre vs. post-practice), days (baseline, 1st Pads-OFF, 1st Pads-ON, 2nd Pads-ON, 3rd Pads-ON, 4th Pads-ON, and post-season), and group (higher vs. lower impact group). Dependent variables were the plasma expression of S100β and PINCH and symptom scores at each time point, pre-post differences in the plasma expression of S100β and PINCH and symptom scores, and head impact kinematics (frequency, sum of peak linear and rotational acceleration). This prospective observational study of 22 Division-I collegiate football players included pre-season baseline, pre-season practices [1 helmet-only and 4 full-gear], and post-season follow-up. Acute subconcussive effects were examined using the data from the first full-gear practice. Cumulative subconcussive effects were examined across the study duration (total 12 time points per player). Blood samples and self-reported symptom scores were obtained and blood biomarkers were assessed for pre-post practices and pre-post season. Plasma S100β expression level was assessed using a sandwich-based enzyme-linked immunosorbent assay. Plasma PINCH expression level was assessed using western blot analysis. An accelerometer-embedded mouth guard was employed to measure impact kinematics including number of impacts (hits), peak linear acceleration (PLA), and peak rotational acceleration (PRA). For examining cumulative effects, based on the previously established cut-off value of 173.5 g, players who were exposed average impact magnitudes below 173.5 g per practice were categorized into lower (n = 8) or greater than 173.5 g were categorized into higher (n = 14) impact groups. Data analysis consisted of descriptive and inferential statistics. Student’s t-tests were used to assess group differences in demographic and head impact kinematic data, acute effects using pre-post practice change in concussion-related symptom scores and biomarker levels, and longer-term effects using pre-post season change in concussion-related symptom scores and biomarker levels. Pearson r correlations were used to examine potential relationship between acute increase in outcome measures and head impact kinematics data. Two-way repeated measures ANOVAs were used to identify cumulative subconcussive effects over time in concussion-related symptoms scores and biomarker levels. If necessary, one-way ANOVA as a function of group was used to identify where cumulative effect began compared to the baseline, using Dunnett’s host-hoc correction. The alpha level was set at p < 0.05. A total of 721 head impacts were recorded from the 22 players during the 5 training camp practices. There were significant differences in head impact kinematics per practice between lower and higher impact groups [number of impacts per practice, 1.3 vs. 10.0 (p < .001); linear acceleration, 36.4 vs. 285.6 g (p < .001); rotational acceleration, 2,048.4 vs. 16,497.31 rad/s2 (p < .001), respectively]. There were no changes in self-reported concussion symptoms across the study duration. While there was no change in longer-term effect between pre-season baseline and post-season follow-up in plasma S100β level, robust and acute increase was observed in post-full gear practice (0.111 + 0.01 ng/ml) compared to pre-practice S100β level, (0.048 + 0.01 ng/ml; p < .0001). The acute increase in plasma S100β was significantly and positively correlated to the number of hits (r = 0.636, p = 0.001), sum of peak linear acceleration (r = 0.570, p = .006), and sum of peak rotational acceleration (r = 0.655, p = 0.001) sustained. For plasma PINCH level, there was a 4-fold increase at post-practice compared to that of pre-practice (p = .037), indicating the acute effect of subconcussive impacts. However, the acute increase in plasma PINCH level was independent from frequency and magnitude of impacts sustained, demonstrated by no statistically significant correlations with the number of hits (r = 0.222, p = .333), sum of peak linear acceleration (r = 0.289, p = .204), and sum of peak rotational acceleration (r = 0.297, p = .191). When players were categorized into the lower and higher impact groups and assessed across the 5 training-camp practices, consistently higher levels of plasma S100β and PINCH were found only in the higher impact group at post-practice compared to the baseline. However, plasma level of S100β and PINCH at pre-practice remained stable from the baseline, suggesting the absence of chronic effect from repetitive head impacts. When season-long effects on plasma S100β and PINCH levels were examined, 10 out of 16 players showed increase in plasma PINCH level at post-season compared to the baseline (p = .039) while no significant difference in plasma S100β level. Results from the current study suggest that subconcussive head impacts do not exert self-claimed concussion-related symptoms; however, blood biomarkers detected noticeable acute changes following repetitive subconcussive impacts. Plasma level of S100β protein can be a potential diagnostic measurement to track acute brain burden, and plasma level of PINCH protein may be reflective of the longer-term cumulative brain damage from repetitive head impacts. / Kinesiology

Background: Subconcussion, a mild traumatic brain injury, is best defined and identified by a lack of observable symptoms after axonal injury from minor head impacts. Subconcussive impacts are believed to accumulate with increased exposure over time, and are likely prodromal in the manifestation of a full-blown concussion. As evidenced by changes to changes in cerebral neurochemistry and structure, it is apparent that although individuals who have accumulated subconcussion may present as asymptomatic for motor and/or cognitive impairment using current clinical assessment tools, there is indication of long-term neurological damage which is presently going unrecognized. Objective: For the reasons stated above, a more sensitive and objective assessment tool is required to assess and recognize prodromal concussion manifestation in at risk populations with the intention of preventing further chronic sequelae. Design: Multiple baseline, time-series with repeated measures. Methods: Balance and bilateral reflex variability was assessed at pre-season and at post-season. Results: The current study identified significant changes to static balance postures (taken from the Balance Error Scoring System) through an objective postural assessment of centre of pressure (COP) and Area of Ellipse (AoE) calculations using a low-cost balance board and basic software interface after a season of accumulated subconcussion in female varsity rugby athletes. Specifically, double stance on the floor worsened by 31% in COPAP (p=.025) and by 26% in COPT (p=.038) and tandem stance on an unstable foam surface worsened by 180% in COPML (p=.014), 175% in COPAP (p=.025) and 141% in COPT (p=.005) between pre-and post-season. Our results indicate that these outcome measures are sensitive and can discriminate underlying balance deficits associated with accumulated subconcussive impacts. An objective measurement of spinal cord excitability through bilateral fluctuations of the Hoffman (H-) reflex in the tibial nerve found significantly elevated pre-season Cross Covariance (CCV) values which were 3x higher than those of a neurologically intact control population, suggesting prior neurological damage in study participants. Conclusion: The current study provides a platform for future research investigating bilateral fluctuation in spinal cord excitability after accumulated subconcussion and confirms balance decrements related to subconcussion can be identified through sensitive and specific measurement tools. / Graduate

BACKGROUND: Sports-related head trauma has become a major public health concern with significant consequences including persistent post-concussion syndrome (pPCS) and chronic traumatic encephalopathy (CTE). pPCS is a condition where symptoms of single concussion persist years beyond the initial injury. CTE has been characterized as a condition with insidious onset following a latent period after substantial exposure to repetitive head impacts (RHI). Timing of symptom onset usually distinguishes these conditions, however in certain clinical situations a definitive diagnosis is not always clear. For these situations, a measurable distinguishing variable is necessary. LITERATURE REVIEW: Concussions are the most common form of traumatic brain injury (TBI) and are associated with a variety of neurological symptoms that usually resolve within weeks. Post-concussion syndrome (PCS) refers to cases where symptoms continue months beyond this window, and pPCS is defined as symptoms continuing over years. These conditions are temporally related single concussive events. CTE is the hallmark condition related to RHI and remains difficult to fully characterize as it currently can only be diagnosed post-mortem. Clinical features of CTE are similar to those of pPCS with notable behavioral/mood symptoms in its earliest stages, and progression to severe cognitive decline over time. Current research has shown executive dysfunction to be a common impairment among these conditions. The difference in level of dysfunction between them, if one exists, is yet to be measured. PROPOSED PROJECT: A cross-sectional analysis of executive function in four groups. A control without history of mTBI or football exposure (Non-Football – pPCS), a second control of asymptomatic subjects with football exposure (Football – pPCS), a group of pPCS patients with non-athletic mTBI history (Non-Football + pPCS), and a group of pPCS patients with football exposure (Football + pPCS). Executive functioning will be evaluated using the BRIEF-A assessment. Results will be compared to determine if significant differences in executive functioning exist between the groups. CONCLUSIONS: With previous studies showing a correlation between CTE pathological stage, worsening executive function, and increased RHI exposure, further investigation into using executive function as a distinguishing variable between early stage CTE and pPCS is warranted. SIGNIFICANCE: Results of this study, if significant, could be applied clinically to assess risk of early stage CTE in athletes with prolonged post-concussion symptoms. If results are not significant, they may still be utilized for a better understanding of the effects of isolated mTBIs and RHI on executive functioning, and provide valuable information for ongoing longitudinal studies.

Subconcussive impacts have become a growing concern particularly with respect to contact sports. It is believed that minimal head impacts can cause cerebral perturbations that initiate an immune response creating a window of vulnerability. Evidence suggests that additional head insults sustained during this window of vulnerability elicit an exaggerated inflammatory response and exacerbate cognitive deficits. Therefore, determining the lower limits of systematic perturbation resulting from low-level impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. However, the vast majority of experimental investigations of subconcussion fail to model single impact events and instead focus on cumulative insults. Additionally, these animal models employ impact magnitudes used to model mild Traumatic Brain Injury. The present investigation aimed to address this gap in knowledge through the utilization of a pneumatically controlled, closed-head, blunt impact device capable of producing repeatable, defined, subconcussive head impacts within a rat model. Thermography was used as a noninvasive measure of inflammation and system perturbations with respect to local (head) and global (thorax and abdomen) temperature changes. Cognitive function was assessed using an Open Field Test and Novel Object Recognition test. Neuroinflammation was measured by assessment of GFAP and iba-1 within the hippocampus and corpus callosum. To investigate the tolerance and the persistence of cerebral vulnerability, measurement outcomes were assessed at six timepoints of recovery, 0, 0.5, 1, 4, 7, and 14 days. Thermal disturbances were detected directly after impact, followed by an apparent recovery, 0.5- and 1-day post-impact. A latent temperature increase was observed after 4- and 7-days of recovery coinciding with decreased risk-avoidance behaviors, a modest upregulation of iba-1, and a marked downregulation of GFAP. Short-term memory deficits became apparent after 7-days of recovery. A decrease in locomotor activity and an upregulation of GFAP was observed concomitant to a persistent decrease in risk-avoidance despite thermal, short-term memory, and iba-1 measurements recovery 14-days post-impact. Overall, these results indicate that low magnitude subconcussive impacts can produce latent thermal, behavioral, and histological disturbances uncharacteristic for a head injury model suggestive of a biomechanical threshold of altered pathodynamics that fail to fully recover after 14 days.

Traumatic brain injury, concussion, and subconcussion are different clinical conditions associated with head injury. These conditions share a common origin, mechanical forces directly or indirectly transmitted to the head. In sports, modalities with high exposure to head traumas require further investigation, especially those in which strikes directly to the head are allowed and a determinant of success, such as combat sports. The causes and effects of brain injuries in combat sports such as Mixed Martial Arts, boxing, Muay Thai, and kickboxing are complex and require a comprehensive investigation of many factors. The objective of this dissertation was to explore the main causes that justify combat sports as the main sport sample when it comes to head injury and the effects of chronic exposure to head trauma in this population. Original studies were developed to assess the head injury risk in competition and in training, the level of knowledge of athletes and coaches, and the consequences of chronic exposure to head traumas in the balance function, brain activity, and spinal cord excitability. The risk of a fight ending due to head strikes in competition is directly related to the weight category, and the risk seems to be exacerbated in female athletes. Combat sports athletes are exposed to numerous strikes to the head in simulated fights on a weekly basis in training, when healthcare professionals are absent. During this time that makes up the bulk of exposures, therefore, athletes and coaches are the ones managing potential cases of concussion. However, coaches are not familiar with assessment tools and don’t often seek out concussion knowledge. Alarmingly, coaches, often prior athletes themselves, are the main source of concussion knowledge for their athletes. High exposure to head trauma both in competition and training in addition to iv poor knowledge and behavior are liable to cause consequences in the nervous system. Athletes chronically exposed to head trauma presented subtle deficits in static balance in the most basic human stance, which is the double-leg over a firm surface. Moreover, while the literature consistently shows impairments in brain function, our study expanded the association between head trauma and nervous system deficits to the least studied component of the nervous system, the spinal cord. While athletic training promotes neuroplastic benefits in spinal cord excitability, these were hindered in a sample of athletes chronically exposed to head traumas. The studies in this dissertation demonstrated that athletes in combat sports are chronically exposed to intentional and repetitive head traumas, and that this exposure is likely associated with long-term functional detriments in balance and spinal cord excitability. / Graduate

L’exposition aux impacts commotionnels et sous-commotionnels est une préoccupation majeure dans les sports de contact en raison de leurs effets néfastes sur la santé cérébrale. Des changements physiopathologiques et neurocognitifs ont été constatés après une seule saison de football chez des athlètes exposés à des coups sous-commotionnels. Vu l'absence d'outils sur les lignes de côtés permettant d'identifier les coups sous-commotionnels potentiellement dangereux, il est crucial de mettre au point des mesures objectives pour évaluer les perturbations neuropsychologiques aiguës associées aux chocs à la tête dans les sports de contact. Cette étude a pour but de documenter l'association entre l'exposition aux impacts à la tête pendant un match de football universitaire et les changements à court terme de l’excitabilité du cortex moteur primaire (M1) à l'aide de la stimulation magnétique transcrânienne (SMT). À cette fin, vingt-neuf athlètes masculins de niveau universitaire ont porté des protège-dents instrumentés (iMG) pendant un match de football afin de mesurer l'exposition aux impacts à la tête. Les mesures SMT ont été effectuées 24 heures avant et 1 à 2 heures après le match. De plus, vingt athlètes de football assigné au groupe contrôle ont participé à une séance d'entraînement physique sans contact et ont effectué les mêmes mesures de SMT. Les résultats suggèrent que, par rapport au groupe contrôle, le groupe d'athlètes ayant joué un match de football présentait une désinhibition intracorticale significative (p=0,028) sur l'inhibition intracorticale à intervalle court (SICI 3-ms) après le match. Par ailleurs, les joueurs de football exposés à un plus grand nombre de coups de 40g+ et à des forces cumulées plus importantes dues à des chocs de 40g+ présentaient une désinhibition intracorticale plus importante après le match. Compte tenu les effets délétères d'une diminution de l'inhibition sur le contrôle moteur et l'équilibre, suivre de manière systématique l'exposition aux impacts à la tête des athlètes tout au long de la saison pourrait s'avérer avantageux pour la gestion clinique des risques de blessure. Ces changements observés renforcent la conviction qu’il est nécessaire d’investiguer davantage les effets à long terme de l’exposition aux impacts sous-commotionnels. / Repetitive head impacts and sport-related concussions are significant concerns in contact sports due to their adverse effects on brain health. Pathophysiological and neurocognitive changes have been found after a single season of football in athletes exposed to subconcussive hits. Considering the lack of sideline tools to identify potentially dangerous subconcussive hits, coming up with objective measures to evaluate acute neurologic impairments associated with head impacts in contact sports is crucial from a clinical standpoint. The current project aimed to investigate the association between head impact exposure (HIE) during a varsity football game and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). To this end, we conducted a study, in which twenty-nine university-level male athletes wore instrumented mouthguards (iMGs) during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Additionally, twenty control football athletes submitted to a non-contact physical training session and underwent identical TMS assessments. Results suggest that relative to controls, the group of athletes who had played a full contact football game exhibited a significant intracortical disinhibition (p=.028) on short-interval intracortical inhibition (SICI 3-ms) within hours following the game. Moreover, football players exposed to more 40g+ hits and greater cumulative forces from 40g+ head impacts exhibited greater post-game SICI disinhibition. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces throughout the course of contact sport season could reveal essential for sideline clinical management of head injury risk. These observed changes add to the concern that more research into the lasting consequences of HIE is needed.