Real world exposures to physiologically and/or psychologically stressful environments are often multifactorial. For example, high-altitude typically combines exposure to hypobaric hypoxia, solar radiation and cold ambient temperatures, while sea level thermal stress is often combined with supplementary or transient stressors such as rain, solar radiation and wind. In such complex environments, the effect of one stressor on performance may be subject to change, simply due to the presence of another independent stressor. Such differential influences can occur in three basic forms; additive, antagonistic and synergistic, each term defining a fundamental concept of inter-parameter interactions. As well as the natural occurrence of stressors in combination, understanding interactions is fundamental to experimentally modelling how multiple physiological strains integrate in their influence on or regulation of - exercise intensity. In this thesis the current literature on neuromuscular fatigue and the influence of thermal and hypoxic stress is reviewed (Chapter 1). This is followed by an outline of the methodological developments used in the subsequent experiments (Chapter 2). In the first experimental study (Chapter 3) a novel approach was adopted to investigate the combined effect of muscle cooling and hypoxia on neuromuscular fatigue in humans. The results showed that the neuromuscular system s maximal force generating capacity declined by 8.1 and 13.9% during independent cold and hypoxic stress compared to control. Force generation decreased by 21.4% during combined hypoxic-cold compared to control, closely matching the additive value of hypoxia and cold individually (22%). This was also reflected in the measurement of mechanical fatigue (electromechanical ratio), demonstrating an additive response during combined hypoxic-cold. From this study, it was concluded that when moderate hypoxia and cold environmental temperatures are combined during low intensity exercise, the level of fatigue increases additively with no interaction between these stressors. Before conducting a more complex investigation on combined stressors, a better understanding of the role of muscle temperature on central fatigue - i.e. voluntary muscle activation via the afferent signalling pathways was sought. The focus of Chapter 4 was to quantify the relationship between muscle temperature and voluntary muscle activation (central fatigue) across a wide range of temperatures. The primary finding was that different muscle temperatures can induce significant changes in voluntary activation (0.5% reduction per-degree-centigrade increase in muscle temperature) when neural drive is sustained for a prolonged effort (e.g. 120-s); however this effect is not exhibited during efforts that are brief in duration (e.g. 3-s). To further explore this finding, Chapter 5 investigated the effect of metaboreceptive feedback at two different muscle temperatures, using post-exercise muscle ischemia, on voluntary activation of a remote muscle group. The results showed that at the same perceived mental effort, peripheral limb discomfort was significantly higher with increasing muscle temperature (2% increase per-degree-centigrade increase). However any influence of increased muscle temperature on leg muscle metaboreceptive feedback did not appear to inhibit voluntary muscle activation - i.e. central control - of a remote muscle group, as represented by an equal force output and voluntary activation in the thermoneutral, contralateral leg. In Chapter 6, the psycho-sensory effects of changes in muscle temperature on central fatigue during dynamic exercise were investigated. During sustained dynamic exercise, fatigue development appeared to occur at a faster rate in hot muscle (4% increase per-degree-centigrade increase) leading to a nullification of the beneficial effects of increased muscle temperature on peak power output after a period of ~60-s maximal exercise. In support of previous studies using isometric exercise (Chapter 4 and 6), participants reported significantly higher muscular pain and discomfort in hot muscle compared to cooler muscle during dynamic exercise (2 and 1% increase per-degree-centigrade increase respectively), however this did not result in a lower power output. From Chapters 4, 5 and 6 it was concluded that in addition to faster rates of metabolite accumulation due to cardiovascular strain, it is possible that a direct sensitisation of the metaboreceptive group III and IV muscle afferents occurs in warmer muscle. This likely contributes to the reduction in voluntary muscle activation during exercise in the heat, while it may attenuate central fatigue in the cold. It was also interpreted that muscle afferents may have a similar signalling role to cutaneous sensory afferents; the latter of which are recognised for their role in providing thermal feedback to the cognitive-behavioural centres of the brain and aiding exercise regulation under thermal stress. The impact of body core and active muscle temperature on voluntary muscle activation represented a similar ratio (5 to 1 respectively) to the temperature manipulated (single leg) to non-temperature manipulated mass (rest of body) in Chapters 4, 5 and 6. This indicates that voluntary muscle activation may also be regulated based on a central meta-representation of total body heat content i.e. the summed firing rates of all activated thermoreceptors in the brain, skin, muscle, viscera and spine. Building on the initial findings of Chapter 3, Chapter 7 investigated the causative factors behind the expression of different interaction types during exposure to multi-stressor environments. This was achieved by studying the interaction between thermal stress and hypoxia on the rate of peripheral and central fatigue development during a high intensity bout of knee extension exercise to exhaustion. The results showed that during combined exposure to moderate hypoxia and mild cold, the reductions in time to exhaustion were additive of the relative effects of hypoxia and cold independently. This differs from the findings in Chapter 3, in which fatigue was additive of the absolute effects of cold and hypoxia. In contrast, combining moderate hypoxia with severe heat stress resulted in a significant antagonistic interaction on both the absolute and relative reductions in time to exhaustion i.e. the combined effect being significantly less than the sum of the individual effects. Based on the results in Chapter 7, a quantitative paradigm for understanding of systematic integration of multifactorial stressors was proposed. This is, that the interaction type between stressors is influenced by the impact magnitude of the individual stressors effect on exercise capacity, whereby the greater the stressors impact, the greater the probability that one stressor will be cancelled out by the other. This is the first study to experimentally model the overarching principles characterising the presence of simultaneous physiological strains, suggesting multifactorial integration be subject to the worst strain takes precedence when the individual strains are severe.

In the stochastic modeling of neurons, the first passage time problem arises as a natural object of study when considering the inter spike interval distribution. In this report, we study some aspects of this problem as it arises in the context of neuroscience. In the first chapter we describe the basic neurophysiology required to model the neuron. In the second, we study the Poisson model, Stein’s model, and some diffusion models, calculating or indicating methods to compute the density of the first passage time random variable or its moments. In the third and fourth chapters, we study the Fokker-Planck equation, and use it to compute the first passage time in the discrete and continuous time random walk cases. In the final chapter, we study sequences of neurons and the change in the density of the waiting time distributions, and hence in the inter spike intervals, as the output spike train from one neuron is considered as the input in the subsequent neuron.

Background: Huntington’s disease (HD) and Parkinson’s disease (PD) are neurodegenerative diseases causing dysfunction and death of cells within the basal ganglia, and thus disruption of pathways with resultant impairment of cognition, motor function, and behavior. These impairments result in decreasing independence in activities of daily living and quality of life even from relatively early in the disease. Among the many motor deficits in HD and PD, impaired gait initiation is a cardinal motor characteristic in both diseases. However, the neurophysiological deficits that underlie gait impairments in people with HD and PD are not well understood. Movement related potentials derived from EEG may insight into the dynamics of areas of the brain involved in motor planning in people with HD and PD. Findings from this study provide a bridge between functional deficits and neuropathology in the progression of HD and has the potential to impact mechanistic understanding of gait initiation in basal ganglia disorders, and inform the development of clinical outcome measures and potential non-invasive biomarkers. The aims of this study were to: 1) identify the differences in movement-related potentials in individuals with manifest HD and mid-stage PD, and non-neurological peers, 2) verify kinetic differences in gait initiation reflective of postural stability in HD and PD, 3) determine force modulation impairments during gait initiation in the mediolateral (ML) and anteroposterior (AP) direction in HD and PD, and 4) determine the tolerance of a high repetition gait initiation protocol. Methods: EEG data were collected for participants for 5 blocks of 15 trials of gait initiation. Kinetic data was collected using an embedded force plate. EEG was time-locked with kinetic data in real-time. RPs amplitudes and latencies, and CNV amplitudes and latencies were determined prior to the onset of the first APA and heel-off. Center of pressure (COP) displacement averages and excursions were determined in the mediolateral (ML) and anteroposterior (AP) direction as measures of postural stability. COP accelerations and coefficient of variance (COV) of force were derived from gait initiation windows in the ML and AP direction as measures of force modulation. Tolerability of the protocol was determined by assessing fatigue from changes in COP averages and excursions from the first block of gait as compared to the last block of gait. Mean values, standard deviations, and mean differences between HD and PD were determined for individual and group data. Results: Three individuals with HD and three with PD were recruited with mean ages of 52.67 and 74.3 respectively. Mean differences and effect sizes indicated that HD participants had a greater average COP in the x direction and greater COP max excursions in the y direction relative to PD participants. PD displayed greater COP max excursions in the y direction relative to HD. There were no differences among COP max measures in the x direction. Similarly, there were no differences between HD and PD participants for CNV amplitudes and latencies, and RP amplitudes and latencies prior to APA onset and heel-off. Among impulse values, there were no differences in ML APA impulse between HD and PD participants, however PD participants exhibited a larger impulse in the AP APA. Lastly, participants were able to tolerate the high repetition protocol as indicated by COP values over three blocks of trials. Discussion: Results confirmed previous findings for kinetic parameters and validated the methodology in its ability to measure movement-related potentials prior to gait initiation in people with HD and PD. No study to date has used wireless EEG technology to measure neural signal in real-time during gait initiation in PD and HD. The values obtained from this system and methods were similar to the results determined in wired and tethered systems. The MRP amplitudes present in the PD participants, along with latencies of MRPs between HD and PD, may indicate potential specificity of MRP responses according to disease-stage and medication-state. Future work will explore the use of MRPs in larger cross-sectional studies and for the development of a meaningful clinical outcome measure.

Le système vestibulaire est le seul sens ne possédant pas un cortex primaire mais plusieurs zones corticales rassemblées sous le terme « cortex vestibulaire ». Le rôle et le fonctionnement du cortex vestibulaire restent peu connus à l’état physiologique, et encore moins chez des personnes souffrant de pathologies vestibulaires ou de l’intégration multisensorielle. Parmi ces régions, l’hippocampe joue un rôle fondamental dans la cognition d’origine vestibulaire et en particulier dans l’orientation spatiale et la formation de carte cognitive. Le but de ce travail était d’étudier la répartition des influx vestibulaires au sein de l’hippocampe, chez le rat qui représente l’espèce où les connaissances sur l’hippocampe sont les plus développées. Pour cela nous avons mis au point une méthode de lésion labyrinthique chirurgicale et une méthode de stimulation électrique sélective de chaque senseur vestibulaire (3 ampoules canalaires, les macules utriculaires et sacculaires). Cette méthode a ensuite été appliquée pour étudier le reflex vestibulo-oculaire spécifique de chaque senseur du rat. Ce reflex vestibulo-oculaire a ensuite était utilisée comme témoin d’une stimulation efficace et sélective de chaque senseur vestibulaire. Nous avons enfin étudié la projection des influx vestibulaires au niveau de l’hippocampe par analyse immunohistochimique de la protéine cFOS, considéré comme un marqueur de l’activité neuronale. Les résultats retrouvent une prédominance de cFOS au niveau de l’hippocampe dorsal, dans la région CA2-CA3. Ces résultats sont cohérents avec l’implication de l’hippocampe dorsal dans la cognition et le rôle de CA3 dans l’encodage de nouvelles informations spatiales, dans la mémoire à court terme et dans la représentation spatiale géométrique de l’environnement. / The vestibular system is the only sense that lake a primary cortex but project to several cortical areas known as the "vestibular cortex". The roles and functioning of the vestibular cortex remain poorly known, neither in the physiological state, nor in pathologies involving the vestibular system. Among these cortices, the hippocampus plays a fundamental role in vestibular cognition and in particular in spatial orientation and cognitive map formation. The purpose of this work was to study the distribution of vestibular inputs within the rat’s hippocampus, which represents the species where hippocampus is best known. For this purpose we have developed a method of surgical labyrinthectomy and a method of selective electrical stimulation of each vestibular sensor (3 canals ampullae, utricular and saccular maculae). This method was then applied to study the vestibulo-ocular reflex specific of each sensor in the rat. This vestibulo-ocular reflex was further used during electrical stimulation of each sensor to control the effectiveness and selectiveness of the stimulation. Finally, we studied the vestibular imputs in the hippocampus by immunohistochemical analysis of the cFOS protein, which is considered as a marker of neuronal activity. The results show a predominance of cFOS labelling in the dorsal hippocampus, in the CA2-CA3 region. These results are consistent with the role of the dorsal hippocampus in cognition and the role of CA3 encoding of new spatial information within short-term memory and in processing the geometry of the environment.

Introduction: Entry-level physical therapist education on pain has been described as lacking. Calls have been made to include pain science courses to address this knowledge gap. Methods: Physical therapist students’ pain knowledge and attitudes were measured using the revised Neurophysiology of Pain Questionnaire (rNPQ) and Pain Attitudes and Beliefs Scale for Physical Therapists (PABS-PT), respectively. Univariate ANOVAs, with post hoc pairwise comparison and effect sizes, were used to measure these aspects over time. Results: Pain knowledge and clinician beliefs were significantly different (p < 0.001) at various curricular timepoints. rNPQ scores increased from 1st to 2nd year (effect size: 1.10), remained similar between years 2 and 3, and improved following the pain course (effect size: 1.25). Biomedical beliefs were similar during years 1, 2 and 3, and declined following the pain course (effect size: 1.56). Conversely, psychosocial belief scores increased from 1st to 2nd year (effect size: 0.82), remained similar between years 2 and 3, and increased following the pain course (effect size: 1.08). Discussion/Conclusions: Physical therapist education, without a dedicated pain science course, may be insufficiently preparing students to treat patients in pain. Educators should consider adopting a dedicated pain science course or substantially bolstering embedded curricular pain content to promote best practice in pain treatment.

Tout comme l’entraînement, la recherche en science du sport est un facteur déterminant de la performance sportive. À travers l’étude d’une activité physique intermittente, le badminton, le prisme des concepts biomécaniques, physiologiques et physiques convergent vers une approche pluridisciplinaire des déterminants de la performance sportive. Ainsi, l’objectif de l’ensemble de ce travail doctoral est, à la fois, la prédiction de la performance en badminton et la compréhension des mécanismes de production d’une vitesse de volant proche des 500 km/h. Les réponses physiologiques et neuromusculaires ont permis la mise en place d’un test discriminant spécifique, prédictif du niveau d’expertise, et proche des situations écologiques d’un match. Paradoxalement, les causes des mécanismes neurophysiologiques liés à la fatigue induite lors d’un match prolongé restent toutefois inconnues. Il apparaît primordial d’approfondir les dits mécanismes vraisemblablement à l’origine de la diminution de la performance sportive. Les évolutions des observables de match, de la force maximale et de la puissance des membres supérieurs et inférieurs convergent vers une diminution progressive au cours de la pratique. Corollairement, la compréhension des mécanismes d’optimisation de la vitesse du volant a permis de mettre en exergue des principes biomécaniques et physiques déterminant lors de la prédiction d’une grande vitesse de volant lors d’une performance maximale. En effet, les principes d’adjonction des segments et d’étirement-renvoi influencent largement la vitesse de la main. En complément, le principe de bras de levier et l’effet élastique de la raquette permettent également d’accroître la vitesse de la raquette. Enfin, la conservation de la quantité de mouvement et le coefficient de restitution contribuent finalement à la vitesse du volant. / Just like training, sport science research is a key factor in sports performance. Through the study of intermittent physical activity, in this case badminton, biomechanical, physiological and physical concepts emerge and offer a multidisciplinary approach of the determinants of sport performance. Thus, the goal of this doctoral work is both the study of badminton in the performance prediction and the understanding of the mechanisms in the production of wheel velocity close to 500 km/h. The physiological and neuromuscular responses enabled the establishment of a specific discriminatory test, predicting the level of expertise, and close to the ecological conditions of a match. Paradoxically, the causes of neurophysiological mechanisms associated with the fatigue induced by a prolonged game remain unknown. It appears heuristic to further study those mechanisms which are at the origin of a decrease in athletic performance. The evolution of observable match variables, the maximum strength and the power of the upper and lower limbs converge towards a gradual decrease in the practice. As a corollary, the understanding of the optimisation of the speed of the flywheel mechanisms helped to highlight the biomechanical and physical principles, essential in predicting a large wheel speed during a maximum performance. Indeed, the principles of adding segments and stretching shortening cycle largely influence the speed of the hand. In addition, the principle of the lever arm and the elastic effect of the racket also increase the speed of the racket. Finally, the conservation of the momentum and the restitution coefficient ultimately contribute to the speed of the shuttlecock.

Le emozioni sono state largamente indagate da discipline differenti che ne hanno evidenziato il ruolo fondamentale nei processi cognitivi, sociali e comportamentali degli individui. Alla luce di queste evidenze, la presente tesi di dottorato si è proposta di indagare, attraverso l’utilizzo di un approccio multimetodologico caratterizzato dall’uso di elettroencefalografia (EEG), spettroscopia funzionale nel vicino infrarosso (fNIRS) e biofeedback, il ruolo e l’influenza delle emozioni in differenti contesti di vita sociale, passando da una prospettiva “intra-soggettiva” ad una “inter-soggettiva”. Nello specifico, il primo studio ha indagato i correlati neurofisiologici impliciti ed espliciti delle risposte emotive caratterizzanti la presa di decisione morale nel singolo individuo. Il secondo studio, attraverso l’utilizzo dell’hyperscanning, ha osservato i correlati neurofisiologici e i meccanismi di sintonizzazione cerebrale e periferica associati alle risposte emotive di individui interagenti durante uno scambio prosociale. Infine, il terzo studio ha investigato i correlati neurofisiologici e i meccanismi di sintonizzazione emotiva sottostanti un’interazione comunicativa non-verbale. In conclusione, i tre studi si sono proposti di osservare, adottando un livello crescente di complessità, da una prospettiva sul singolo individuo ad una diadica, come l’utilizzo di un approccio multimetodologico possa informare sui meccanismi impliciti ed espliciti delle risposte emotive durante differenti situazioni sociali. / Emotions have been extensively investigated by different disciplines, highlighting their fundamental role in individuals’ cognitive, social and behavioral processes. In light of this evidence, the present doctoral thesis aims to investigate, through the use of a multimetodological approach characterized by the use of electroencephalography (EEG), functional Near-Infrared Spectroscopy (fNIRS), and biofeedback, the role and influence of emotions in different contexts of social life, passing from an “intra-subjective” to an “inter-subjective” perspective. Specifically, the first study has investigated the implicit and explicit neurophysiological correlates of emotional responses characterizing moral decision-making in single individuals. The second study, through the use of the hyperscanning paradigm, has observed the neurophysiological correlates and the brain and peripheral tuning mechanisms associated with emotional responses of interacting individuals during a prosocial exchange. Finally, the third study has investigated the neurophysiological correlates and emotional synthonization mechanisms underlying a non-verbal communicative interaction. In conclusion, the three studies set out to observe, adopting an increasing level of complexity, from a single individual to a dyadic perspective, how using a multimetodological approach can inform about the implicit and explicit mechanisms of emotional responses during different social situations.

Using functional magnetic resonance imaging in humans, Brodmann's area 5 (BA5) is observed to be activated during the suppression of motor output in the context of a NO-GO task. In monkeys, BA5 is associated with somatosensation and specifically linked with motor preparation. The goal of this thesis is to investigate BA5 influences on corticospinal excitability prior to the onset of movement, in the context of a GO/NO-GO paradigm. To achieve this goal, paired-pulse TMS is used to probe the functional connectivity between BA5 and ipsilateral primary motor cortex (M1) for a muscle specific to the hand. Three experiments are performed that investigate the differences in corticospinal output to the hand in a GO task versus a NO-GO task and the stimulation parameters that reveal such differences. Results indicate that BA5 is able to condition M1 prior to movement in a task-specific manner. Further, motor evoked potentials (MEPs) are suppressed in the context of a NO-GO task relative to a GO task, and task-specific differences rely on the intensity and direction of induced current in the cortex. In conclusion, data from this thesis contribute to our understanding of the role of BA5 in motor control. / Thesis / Master of Science in Kinesiology

No description available.

<p>The lateral superior olive (LSO) is an auditory brainstem nucleus crucial in the determination of sound source. To accomplish sound localization, principal neurons of the LSO compare the intensity of sounds reaching the two ears by integrating an excitatory input from the ipsilateral anteroventral cochlear nucleus (AVCN), which is activated by sound reaching one ear, with an inhibitory input from the ipsilateral medial nucleus of the trapezoid body (MNTB), which is activated by sound reaching the opposite ear. In order for LSO principal neurons to properly integrate these excitatory and inhibitory inputs, the inputs must be matched in a frequency-dependent matter to LSO neurons. The mechanisms that direct the organization, selection, and maturation of both the excitatory and inhibitory pathway during development are not well understood. The experiments presented in this thesis were aimed at understanding the mechanisms that may underlie these processes in the developing LSO.</p> <p>The excitatory neurotransmitter glutamate is released in both the excitatory AVCN-LSO pathway and the inhibitory MNTB-LSO pathway during their period of functional circuit refinement, and may be important in the development of both of these pathways. Using the patch-clamp technique in acute brainstem slices of rats, we evaluated glutamatergic transmission in both the excitatory AVCN-LSO pathway and the inhibitory MNTB-LSO pathway during their period of functional refinement. Additionally, using the patch-clamp technique in acute brainstem slices of mice, we examined what functions vesicular glutamate transporter 3 (VGlut3), the protein that supports glutamate release from MNTB terminals, may have in the developing MNTB-LSO pathway. When taken together, the results from the three studies presented support a model in which circuit maturation in the LSO relies on mechanisms driven through a specific glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor.</p> / Doctor of Philosophy (PhD)