Les études neurophysiologiques de la locomotion ont été en très grande majorité conduites chez l’animal. Elles ont permis de mettre en évidence une région locomotrice dans le mésencéphale, dans laquelle le noyau pédonculopontin (NPP) joue un rôle prépondérant. Des troubles de la marche et de l’équilibre dans la maladie de Parkinson sont en lien avec la perte de neurones cholinergiques dans le NPP, mais également avec la dysfonction dopaminergique dans les ganglions de la base. L’activité du noyau subthalamique (NST) est impactée par la perte dopaminergique. Recevant de nombreuses afférences corticales et ayant une connectivité réciproque forte avec le PPN, la connectivité du NST suggère son importance pour le contrôle locomoteur. Néanmoins, il existe peu de données sur le rôle du NST et du NPP dans le contrôle de la marche et de l’équilibre chez l’Homme. Ce manuscrit regroupe des enregistrements électrophysiologiques du NST pendant l’initiation de la marche, une étude de l’effet de la fréquence de la stimulation cérébrale profonde du NST sur l’initiation de la marche en contexte de charge cognitive, une étude par immunohistochimie de la région du NPP chez l’Homme, et des données préliminaires d’activité électrophysiologique du NPP pendant une tâche de marche imaginaire et l’initiation de la marche. Ensemble, ces données participent à une meilleure compréhension des bases anatomo-fonctionnelles du contrôle de la marche et de l’équilibre chez l’Homme. De plus, la mise en évidence de marqueurs électrophysiologiques des troubles de la marche et de l’équilibre laisse à penser que la prise en charge de ces troubles est possible par stimulation cérébrale profonde. / Neurophysiological studies of locomotion have been in majority driven on animal models. These approaches led to the identification of a mesencephalic locomotor region in which the pedonculopontin nucleus (PPN) plays a preponderant role. Gait and posture disabilities in Parkinson’s disease were linked with a loss of cholinergic neurons in the PPN as well as a dopaminergic dysfunction in the basal ganglia. The activity in the subthalamic nucleus (STN) is impacted by the dopaminergic loss. The STN receives numerous cortical inputs and is reciprocally connected with the PPN, suggesting an important role of the STN in the locomotor control. However, few data exist on the role of the STN and the PPN in gait and balance control in humans. This manuscript regroups electrophysiological recordings of the STN during gait initiation, a study of the effect of deep brain stimulation frequency of gait initiation in the context of cognitive load, an immunochemistry study of the region of the PPN in human, and preliminary results of the electrophysiological activity of the PPN during virtual gait and real gait initiation. Together, these data participate to a better understanding of the anatomo-functional basis of the gait and balance control in human. Moreover, the identification of electrophysiological markers of gait and balance dysfunction suggest that a deep brain stimulation may be relevant for their alleviation.

O estudo do controle neurofisiológico do movimento tem sido realizado sob várias perspectivas. Experimentos com seres humanos são realizados durante a execução de uma dada tarefa motora e, frequentemente, mediante a aplicação de estímulos externos (elétrico, magnético ou mecânico) ao sistema neuromuscular. Estes experimentos fornecem uma grande quantidade de dados referentes ao funcionamento das redes neuronais e dos atuadores biomecânicos envolvidos nos procedimentos. Entretanto, alguns achados experimentais permanecem incompreensíveis, requerendo a utilização de outros recursos para elucidar quais mecanismos estão por trás dos resultados. Neste sentido, a modelagem matemática e a simulação computacional servem como parte importante destas ferramentas que são imprescindíveis para uma melhor compreensão dos mecanismos neurofisiológicos e biomecânicos por trás do controle do movimento. A presente tese de doutorado teve como objetivo prover um modelo neuromusculoesquelético biologicamente plausível capaz de investigar diferentes mecanismos responsáveis pelo controle do torque gerado na articulação do tornozelo. Este modelo teve como base um modelo neuromuscular previamente proposto, porém, que não incorporava uma série de elementos fundamentais para um estudo mais amplo do sistema motor. O novo modelo proposto contempla modelos de motoneurônios com dendritos ativos, proprioceptores musculares responsáveis pelas vias reflexas de curta e média latência, modelos que representam as características viscoelásticas dos músculos e um modelo biomecânico do ser humano durante a postura ereta quieta. O modelo foi aplicado a diferentes problemas relacionados ao funcionamento do sistema neuromusculoesquelético, que são tipicamente explorados por experimentos com seres humanos, e forneceu bases teóricas importantes para estes achados. / The neurophysiological control of movement has been studied from several standpoints. Human experiments are performed during the execution of a given motor task and, frequently, by applying an external stimulation (electrical, magnetic, or mechanical) to the neuromuscular system. These experiments provide a large amount of data concerning the functioning of the neuronal networks and biomechanical actuators involved in the procedures. Nonetheless, some experimental findings remain puzzling, so that other available resources should be used to clarify what mechanisms are behind these results. In this vein, the mathematical modeling and computer simulations are invaluable tools that may be used to better understand the neurophysiological and biomechanical mechanisms underlying the motor control. The present PhD thesis aimed at providing a biologically plausible neuromusculoskeletal model that was used to study different mechanisms involved in the control of the ankle joint torque. This model was based on a previous neuromuscular model, which did not employ several elements that are fundamental to a comprehensive evaluation of the motor system. The novel proposed model encompasses motor neuron models with active dendrites, muscle proprioceptors responsible for the short- and medium-latency reflex pathways, muscle models with the main viscoelastic features, and a biomechanical model of the human body during upright stance. It was applied to a series of problems frequently related to the functioning of the neuromusculoskeletal system and its main outcomes provided important theoretical bases for a set of experimental findings.

A ocorrência de potenciais de ação e neurotransmissores, componentes principais do sistema nervoso animal, em plantas, bactérias e fungos mostra a universalidade dos princípios de sinalização e transmissão de informações na forma de sinais químicos e elétricos em todos os organismos. Esses tópicos de estudo, juntamente com inteligência em plantas e transporte vesicular de auxina, constituem as linhas de pesquisa principais da recém-criada Neurobiologia Vegetal. Entre os neurotransmissores encontrados em plantas, a acetilcolina atua, entre outras situações, no crescimento e desenvolvimento controlado pelo fitocromo e na permeabilidade iônica de membranas. Nesse contexto, foi sugerido que a acetilcolina pode desempenhar um papel importante na regulação do movimento estomático, tendo efeito estimulatório na abertura dos estômatos além de poder atuar na sinalização entre raiz e parte aérea. Dessa forma, foi proposto identificar a presença deste neurotransmissor em plantas de milho hidratadas e submetidas a estresse hídrico, com o objetivo de correlacionar a presença de acetilcolina com as respostas estomáticas de tais plantas. Além disso, foi objetivo do trabalho avaliar parâmetros fisiológicos como potencial hídrico, condutância estomática, transpiração e fotossíntese líquida e suas possíveis relações com a acetilcolina em três folhas das plantas hidratadas e estressadas. Para tanto, foi montado um experimento em blocos casualizados em esquema fatorial (2x3). Os fatores foram: água, nos níveis de hidratação e estresse, e idade das folhas nos níveis folha 4 (mais velha), folha 5 (idade intermediária) e folha 7 (mais jovem). As plantas foram divididas em 20 blocos, contendo uma planta hidratada e uma sob estresse cada e as análises fisiológicas feitas nas três folhas. As plantas foram colocadas em câmara de crescimento tipo BOD com controle de iluminação e temperatura. Após análises fisiológicas, as folhas foram utilizadas para extração e determinação de acetilcolina. Os extratos purificados e secos foram submetidos à pirólise e cromatografia gasosa e as substâncias identificadas por espectrometria de massas. Não foi detectada acetilcolina nas plantas, apesar de estudos anteriores demonstrarem sua ocorrência em folhas e sementes de milho. Hipóteses foram levantadas para explicar tal fato. Quanto as variáveis fisiológicas, o déficit hídrico reduziu em aproximadamente 59% a transpiração, em 65% a condutância estomática e em 59% a fotossíntese das plantas. Condutância estomática e transpiração, condutância e fotossíntese, e transpiração e fotossíntese apresentaram intensa correlação. Já o potencial hídrico teve baixa correlação com essas variáveis. Quanto ao fator idade, folhas 7 apresentaram maiores valores de fotossíntese, condutância e transpiração que as folhas 4 e 5. / The occurrence of action potential and neurotransmitters, the major components of animal nervous system, in plants, bacteria and fungi, shows the universality of signaling principles and information transmission in the way of chemical and electrical signals in all organisms. These study topics, along with plant intelligence and vesicular-based auxin transport, constitute the major research lines of the newly created Plant Neurobiology. Among the neurotransmitters found in plants, the acetylcholine plays a role in phytochromecontrolled growth and development and in membrane ion permeability. In this context, it was suggested that acetylcholine can play an important role in the regulation of stomatal movements, having stimulatory effect in the stomatal opening. In addition it can play a role in root-to-shoot signaling process. Therefore, it was proposed to identify the presence of this neurotransmitter in maize plants hydrated and under water stress, with the aim of correlating the presence of acetylcholine with the stomatal responses of such plants. Moreover, another aim of the study was to evaluate physiological parameters like water potential, stomatal conductance, transpiration rate and net photosynthetic rate and their possible relationship with the acetylcholine in three leaves of hydrated and stressed plants. Therefore, an experiment was set up in randomized block design in 2x3 factorial. The factors were: water, in the levels of hydration and stress, and leaves age in the levels leaf 4 (older), leaf 5 (intermediary age) and leaf 7 (younger). The plants were divided in 20 blocks, and each one has had one hydrated plant and one stressed plant and the physiological analysis was made in three leaves. The plants were placed in B.O.D. growth chamber under controlled conditions of light and temperature. After the physiological analysis, the leaves were used to extraction and determination of acetylcholine. The dried and purified extracts were subjected to pyrolysis and gas chromatography and the substances identified by mass spectrometry. The acetylcholine was not detected in plants, although earlier studies have had demonstrated its occurrence in maize leaves and seeds. Hypotheses were elaborated to explain such fact. Regarding the physiological variables, water stress reduced the plants transpiration rate in 59%, stomatal conductance in 65% and net photosynthesis in 59%. Stomatal conductance, transpiration and photosynthesis were strongly related. On the other hand, the water potential showed weak correlation with that variable. As for the age factor, leaves 7 had higher photosynthetic rates, conductance and transpiration than the leaves 4 and 5.

Remembering previously experienced events can happen as a result of an effortful retrieval attempt. At other occasions, a memory can enter our minds without any apparent effort – or, indeed, intention - to retrieve. Although it has long been appreciated that retrieval from episodic memory is intertwined with cognitive control, the neural mechanisms of memory-control interactions remain unclear. In this thesis I have used functional magnetic resonance imaging (fMRI) and scalp-recorded event-related potentials (ERP) to study the neural basis of episodic retrieval at varying levels of cognitive control. The dorsolateral prefrontal cortex (dlPFC) has been suggested to support a cognitive control mechanism (context processing) which is relevant during various situations that demand maintenance of current goals and rules. Although increased dlPFC recruitment with increasing context processing demands has been demonstrated during episodic retrieval, there are relatively few studies directly comparing the engagement of dlPFC during episodic retrieval with that during other task domains. In Study I, context processing demands were amplified in episodic retrieval, auditory attention and emotion regulation tasks. This led to overlapping dlPFC recruitment in the first two domains and a divergent reliance on ventromedial prefrontal cortex in the emotion domain. Thus, when selection between competing representations needs to be carried out in accordance with the currently relevant goals and task rules, the episodic memory system interacts with domain-general cognitive control mechanisms. Studies II and III explored the reactive nature of retrieval-specific control mechanisms: can we flexibly switch between semantic and episodic retrieval based on the information extracted from a retrieval cue? This was studied using a recognition memory task where the relevant information could with equal probability be supplied by the semantic or the episodic memory system. The fMRI results (Study II) showed that the brain activation during the ‘episodic’ but not the ‘semantic’ trials was expressed in the right prefrontal cortex. As the order of trials was unpredictable, the corresponding changes in brain activation might be evoked by differences in early cue-trace interactions. An event-related potential study (Study III) with the same experimental protocol as in Study II showed that neural processing corresponding to the two trial types diverged as early as in the time window 100-140 ms post-cue onset, thus highlighting the importance of early cue-trace matching in the selection of further retrieval processing. Study IV explored incidental episodic retrieval. Although this form of retrieval is a common experience in everyday life and a disturbing symptom in some psychiatric conditions, it is not clear how such spontaneous expressions of memory are initiated and to what extent the prefrontal cortex is engaged. The fMRI results showed, consistent with Study I, that dlPFC is specifically associated with the intention to retrieve, independently of success. Retrieval success engaged similar networks for incidentally as well as intentionally retrieved memories, comprising the hippocampus, precuneus, ventrolateral PFC, and the anterior cingulate cortex. Collectively, the fMRI and ERP results indicated that incidental retrieval was initiated by early (< 200 ms) oldness estimation carried out on the semantic information extracted from the retrieval cues. Taken together, the results of this thesis indicate that episodic retrieval can be initiated via two routes:  a bottom-up input rising early during the cue processing, and a top-down input provided by the cognitive control processes mediated by the prefrontal cortex.

The dramatic feeding-related activities of the Chagas' disease vector, Rhodnius prolixus are under neurohormonal regulation of serotonin and various neuropeptides. One such family of neuropeptides, the insect kinins, possesses diuretic, digestive and myotropic activities in many insects. In R. prolixus, they co-localize with the corticotropin-releasing factor (CRF)-like diuretic hormone (DH) in neurosecretory cell bodies and their abdominal neurohaemal sites. Additionally, kinins are present in endocrine cells of the midgut and are known to stimulate hindgut and midgut contractions. Through the experimentation presented in this dissertation, the cloning and spatial expression of the R. prolixus kinin (Rhopr-kinin) transcript is described. Physiological bioassays demonstrate the myostimulatory effects of selected Rhopr-kinin peptides and also illustrate the augmented responses of hindgut contractions to co-application of Rhopr-kinin and Rhopr-CRF/DH. The irreversible effects of two synthetic kinin analogs on the hindgut relative to the native kinins also exhibit the prospective biotechnological significance of this study.

The dramatic feeding-related activities of the Chagas' disease vector, Rhodnius prolixus are under neurohormonal regulation of serotonin and various neuropeptides. One such family of neuropeptides, the insect kinins, possesses diuretic, digestive and myotropic activities in many insects. In R. prolixus, they co-localize with the corticotropin-releasing factor (CRF)-like diuretic hormone (DH) in neurosecretory cell bodies and their abdominal neurohaemal sites. Additionally, kinins are present in endocrine cells of the midgut and are known to stimulate hindgut and midgut contractions. Through the experimentation presented in this dissertation, the cloning and spatial expression of the R. prolixus kinin (Rhopr-kinin) transcript is described. Physiological bioassays demonstrate the myostimulatory effects of selected Rhopr-kinin peptides and also illustrate the augmented responses of hindgut contractions to co-application of Rhopr-kinin and Rhopr-CRF/DH. The irreversible effects of two synthetic kinin analogs on the hindgut relative to the native kinins also exhibit the prospective biotechnological significance of this study.

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) contrast has become a widespread technique in brain research. The central challenge in fMRI is the detection of relatively small activity-induced signal changes in the presence of various other signal fluctuations. Physiological fluctuations due to respiration and cardiac pulsation are dominant sources of confounding variability in BOLD fMRI. This dissertation seeks to characterize and compensate for non-neural physiological fluctuations in fMRI. First, the dissertation presents an improved and generalized technique for correcting T1 effect in cardiac-gated fMRI data incorporating flip angle estimated from fMRI dataset itself. Using an unscented Kalman filter, spatial maps of flip angle and T1 relaxation are estimated simultaneously from the cardiac-gated time series. Accounting for spatial variation in flip angle, the new method is able to remove the T1 effects robustly, in the presence of significant B1 inhomogeneity. The technique is demonstrated with simulations and experimental data. Secondly, this dissertation describes a generalized retrospective technique to precisely model and remove physiological fluctuations from fMRI signal: Physiological Impulse Response Function Estimation and Correction (PIRFECT). It is found that the modeled long-term physiological fluctuations explained significant variance in grey matter, even after removing short-term physiological effects. Finally, application of the proposed technique is observed to substantially increase the intra-session reproducibility of resting-state networks.

En situation de perception audiovisuelle de la parole, comme lors des conversations face-àface,nous pouvons tirer partie des informations visuelles fournies par les mouvements orofaciauxdu locuteur. Ceci améliore l’intelligibilité du discours. L'objectif de ce travail était dedéterminer si ce « bénéfice audiovisuel » permet de mieux identifier les phonèmes quin’existent pas dans notre langue. Nos résultats révèlent que l’utilisation de l’informationvisuelle permet de surmonter les difficultés posées par la surdité phonologique dont noussommes victimes lors d'une présentation auditive seule (Etude 1). Une étude EEG indique quel’apport des informations visuelles au processus d’identification de phonèmes non natifspourrait être dû à une modulation précoce des traitements effectués par le cortex auditifprimaire (Etude 2). En présentation audiovisuelle les phonèmes non natifs donnent lieu à uneP50, ce qui n’est pas observé pour les phonèmes natifs. Il semblerait également quel'expérience linguistique affecte l'utilisation des informations visuelles puisque des bilinguesprécoces semblent moins aptes à exploiter ces indices pour distinguer des phonèmes qui neleur sont pas familiers (Etude 3). Enfin, l’étude de l’identification de consonnes plosivesnatives avec une tâche de dévoilement progressif nous a permis d’évaluer la contributionconjointe et séparée des informations auditives et visuelles (Etude 4). Nous avons observé quel’apport de la modalité visuelle n’est pas systématique et que la prédictibilité de l’identité duphonème dépend de la saillance visuelle des mouvements articulatoires du locuteur. / During audiovisual speech perception, like in face-to-face conversations, we can takeadvantage of the visual information conveyed by the speaker's oro-facial gestures. Thisenhances the intelligibility of the utterance. The aim of this work was to determine whetherthis “audiovisual benefit” can improve the identification of phonemes that do not exist in ourmother tongue. Our results revealed that the visual information contributes to overcome thephonological deafness phenomenon we experience in an audio only situation (Study 1). AnERP study indicates that this benefit could be due to the modulation of early processing in theprimary auditory cortex (Study 2). The audiovisual presentation of non native phonemesgenerates a P50 that is not observed for native phonemes. The linguistic background affectsthe way we use visual information. Early bilinguals take less advantage of the visual cuesduring the processing of unfamiliar phonemes (Study 3). We examined the identificationprocesses of native plosive consonants with a gating paradigm to evaluate the differentialcontribution of auditory and visual cues across time (Study 4). We observed that theaudiovisual benefit is not systematic. Phoneme predictability depends on the visual saliencyof the articulatory movements of the speaker.

Carpal tunnel syndrome (CTS) is one of the most common injuries responsible for lost time claims to the Workplace Safety and Insurance Board (WSIB). The main purpose of this study was to determine whether measurable sensorimotor changes exist in asymptomatic individuals who are at risk for CTS such that sensory impairment and/or functional tests may be used in the early detection and intervention to reduce the impact of CTS on individuals, industry and the health care system. Participants were recruited into three strata: (1) individuals diagnosed with mild CTS, (2) asymptomatic individuals who were deemed to be at risk of developing CTS due to exposure to etiological risk factors and (3) asymptomatic individuals who were deemed to be at minimal risk of developing CTS based on non-exposure to risk factors. The main outcome measures included two-point discrimination ability, pressure acuity, vibration sense, Purdue Pegboard Test performance and tracking error and tracking variance on a manual tracking task performed at two different speeds. Seven individuals with CTS, fourteen individuals at risk of developing CTS and nine control individuals with minimal risk participated. The CTS group was significantly different from the at-risk and control groups on the main and work sections of the DASH questionnaire, and the symptom severity scale and functional status scale of the Boston Carpal Tunnel Questionnaire. The only outcome measure that showed a significant difference between the at-risk and the minimal risk group was the assembly task of the Purdue Pegboard Test (p = 0.044), however other measures including median nerve conduction latencies, and manual tracking abilities showed promise that with further recruitment, a significant difference may be seen. The sensory impairment tests did not demonstrate degradation in sensory function in individuals at risk of developing CTS, however analysis of sensory nerve conduction latencies and some aspects of fine motor skills testing did show some promise in their ability to detect individuals at risk of developing CTS. A future prospective study that follows individuals at risk of developing CTS may determine that it is possible to implement a screening tool for the early identification and treatment of CTS. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2009-09-15 12:15:45.208

The neural and sensory mechanisms underlying appropriate muscle recruitment in response to balance challenges remains elusive. We asked whether the decerebrate cat preparation might be employed for further investigation of postural mechanisms. First, we evaluated the muscular activation patterns and three-dimensional whole limb forces generated by a modified premammillary decerebrated cat. We hypothesized that directionally appropriate muscle activation does not require the cerebral cortices. Furthermore, we hypothesized that the muscle responses would generate functionally appropriate and constrained force responses similar to those reported in the intact animal. Data confirmed both of our hypotheses and suggested important roles for the brainstem and spinal cord in mediating directionally appropriate muscular activation. Second, we investigated how individual muscle activation is translated to functional ground reaction forces. We hypothesized that muscles are selectively activated based upon their potential counteractive endpoint force. Data demonstrated that the endpoint force generated by each muscle through stimulation was directed oppositely to the principal direction of each muscle's EMG tuning curve. Further, muscles that have variable tuning curves were found to have variable endpoint forces in the XY plane. We further hypothesized that the biomechanical constraints of individual muscle actions generate the constrained ground reaction forces created in response to support surface perturbations. We found that there was a lack of muscles with strong medial-lateral actions in the XY plane. This was further exaggerated at long stance conditions, which corresponds to the increased force constraint present in the intact animal under the same conditions. Third, we investigated how loss of cutaneous feedback from the footpads affects the muscle recruitment in response to support surface perturbations. We utilized our decerebrate cat model as it allows 1) isolation of the proprioceptive system (cutaneous and muscle receptor) and 2) observation of the cutaneous loss before significant compensation by the animal. We hypothesized that muscle spindles drive directionally sensitive muscle activation during postural disturbances. Therefore, we expected that loss of cutaneous feedback from the foot soles would not alter the directional properties of muscle activation. While background activity was significantly diminished, the directionally sensitive muscular activation remained intact. Due to fixation of the head, the decerebrate cat additionally does not have access to vestibular or visual inputs. Therefore, this result strongly implicates muscle receptors as the primary source of directional feedback. Finally to confirm that muscle receptors, specifically muscle spindles, are capable of generating feedback to drive the directionally tuning, we investigated the response properties of muscle spindles to horizontal support surface perturbations in the anesthetized cat. As previously stated, we hypothesized that muscle spindles provide the feedback necessary for properly directed muscular responses. We further hypothesized that muscle spindles can relay feedback about the perturbation parameters such as velocity and the initial stance condtion. Results confirmed that muscle spindle generate activation patterns remarkably similar to muscular activation patterns generated in the intact cat. This information, along the knowledge that cutaneous feedback does not substantially eliminate directional tuning, strongly suggests that muscle spindles contribute the critical directional feedback to drive muscular activation in response to support surface perturbations.