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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

The role of the primary motor cortex (M1) in volitional and reflexive pharyngeal swallowing.

Al-Toubi, Aamir Khamis Khalfan January 2013 (has links)
Background and aims: The primary motor cortex (M1) controls voluntary motor behaviours. M1 has been identified to play a major role in the execution of voluntary corticospinal tasks as well as self-initiated corticobulbar tasks. However, the involvement of M1 in more complex corticubulbar tasks, such as swallowing, is not yet fully understood. Swallowing is quite different from other voluntary motor tasks as it has both voluntary and reflexive components. The degree of M1 involvement in the pharyngeal, or more reflexive, component of swallowing is unclear. Studies investigating the role of M1 in swallowing have yielded contradictory findings regarding the specific functional contribution of M1 to swallowing. Therefore, further investigation is warranted to clarify the role of M1 in pharyngeal swallowing. Discrete saliva or water swallowing has been utilized in most studies investigating neurophysiology of swallowing in health and disease. However, individuals most frequently complete multiple, consecutive swallows during the ingestion of liquid. Biomechanical differences between discrete and continuous water swallows have been identified using videofluoroscopic swallowing study (VFSS). However, no studies have investigated the pharyngeal pressure differences between these two swallowing tasks. Additional insights into task differences may be revealed through evaluation of pharyngeal pressure utilizing pharyngeal manometry. This research programme sought to clarify the role of M1 in reflexively and volitionally initiated pharyngeal swallowing. In order to understand M1 involvement in the execution of swallowing, comparative tasks that require known dependence on M1 were also included in this research programme. This research programme addressed the biomechanical changes in motor behaviours as a result of neural disruption during the performance of a number of motor tasks. This neural disruption was intrinsically generated through application of dual task (DT) paradigm and extrinsically generated using single pulse transcranial magnetic stimulation (TMS). A secondary aim of this research programme was to identify the differences in pharyngeal pressure generation between discrete and continuous swallowing. Methods: Twenty-four right handed participants (12 males, average age= 24.4, SD= 6.3) were recruited to this research programme. A number of motor tasks that vary in complexity were tested. These tasks included: volitional swallowing, reflexive swallowing, eyebrow movement, jaw movement and finger tapping with right, left, or bilateral index fingers. Participants performed multiple trials of several tasks in each study. Repetitions of tasks during a single session may affect performance due to factors such as fatigue or practice. A baseline study was undertaken to determine within-participant variability of measures across repeated trials. Following the baseline study, the role of M1 in pharyngeal swallowing was investigated in two main studies in counter balanced order. The role of M1 in pharyngeal swallowing was evaluated by investigating swallowing parameters during neural disruption using a DT paradigm. Participants performed tasks in isolation (baseline) and with interference that consisted of pairing swallowing with comparative task that activates M1 (fingers tapping and eyebrow movement tasks). In the other study, single pulse TMS was utilized to create an electrophysiological disruption to the areas of M1 associated with muscular representation of a number of motor behaviours (swallowing tasks, jaw movement and fingers tapping tasks). Stimulation was provided to both hemispheres in random order to evaluate laterality effects. Swallowing parameters and the performance of the other motor tasks were evaluated when performed with and without electrophysiological disruption. Differences in pharyngeal pressure generation between discrete and continuous swallowing were investigated using pharyngeal manometry. Pharyngeal pressures were recorded at three locations: upper pharynx, mid-pharynx and upper esophageal sphincter (UES) during four swallowing types: discrete saliva swallowing, discrete 10 ml swallowing, volitional continuous swallowing, and reflexive continuous swallowing. The research paradigm used in this research programme identified the effect of experimental conditions on the rate and regularity of task performance. In addition, pharyngeal manometry was utilised to measure the effect of experimental conditions on the pattern of the pharyngeal pressure generation during swallowing. Within subject differences from baseline were identified by means of Repeated Measures Analyses of Variance (RM-ANOVA). Results: Initial analysis of the data revealed that repetition of tasks within a session did not affect the rate and regularity of voluntary corticospinal tasks, voluntary corticiobulbar tasks nor swallowing tasks. In addition, repeating the swallowing tasks during a session did not affect pharyngeal pressure as measured by pharyngeal manometry. When motor tasks were performed concurrently in the DT paradigm, rate and regularity of eyebrow movements were significantly decreased when paired with swallowing tasks, whereas rate and regularity of swallowing were significantly decreased when paired with left finger tapping, but not right finger tapping. However, there was no significant effect of any task on the pattern of pharyngeal pressure generation. Extrinsically generated disruption using TMS significantly reduced rate and regularity of finger tapping tasks and regularity of jaw movement and swallowing tasks. In addition, interruption of pharyngeal M1 during the volitional swallowing task produced significant increase in the duration but not the amplitude of the pharyngeal pressure. Pharyngeal pressure generation differed between swallowing types and boluses types, in that saliva swallowing produced longer pharyngeal pressure duration and lower nadir pressure than water swallows. Discrete water bolus swallowing produced longer UES opening compared to both saliva swallowing or continuous water swallowing. Conclusion: The results of this research programme provided valuable methodological information regarding the effect of trials on task performance as well as identifying pharyngeal pressure differences between discrete and continuous swallowing. In addition to the methodological contribution, this research programme expanded on previous knowledge of neural control of swallowing, in that it extended the findings regarding potential role of M1 in pharyngeal swallowing. Given the absent effect of task repetition on the performance of corticospinal and corticobulbar motor tasks, it is speculated that outcomes of research investigating the effect of experimental manipulation on motor tasks performance is due to the experimental tasks, rather than natural variance in the data. The effect of swallowing on the rate and regularity of eyebrow movement, when performed concurrently using DT paradigm, suggest bilateral functional overlapping to a significant degree between neural substrates that control swallowing and orofacial muscles. These results offer partial support of bilateral representation of swallowing in the cortex. In addition, results further revealed potential involvement of right M1 in the regulation of pharyngeal swallowing as evidenced by a disruptive effect of left finger tapping on the rate and regularity of swallowing. The results from the hemispheric TMS disruption study support the active involvement M1 in the execution of voluntary corticospinal and corticobulbar motor tasks. In addition, the current findings extended previous knowledge of neural control of pharyngeal swallowing by documenting the effect of neural disruption on the regularity and pharyngeal pressure measures during volitional and reflexive swallowing. The current programme documented potential role of M1 in the control of pharyngeal swallowing possibly by modulating the motor plan at the swallowing CPG in the brainstem. This project is the first to document pharyngeal pressure differences between discrete and continuous swallowing. These findings contribute valuable information to the swallowing literature as limited number of studies investigated the biomechanical differences between discrete and continuous liquid ingestion. This knowledge will assist clinicians and researchers in identifying the pharyngeal pressure differences between normal and abnormal swallowing in different swallowing types and ultimately guide their rehabilitation decisions. Data from this research programme will add to the existing knowledge of neurophysiology of swallowing, thereby facilitating understanding of swallowing pathophysiology which is crucial for appropriate management of swallowing disorders.
32

Influence des modalités de contraction musculaire sur les effets neuroplastiques de l'exercice / Influence of the muscle mode of contraction on the exercise induced neuroplastic effects

Garnier, Yoann 08 November 2018 (has links)
Parallèlement aux adaptations cardiovasculaires et neuromusculaires, les exercices mono-articulaires ou locomoteurs peuvent induire des changements neuroplastiques de muscles impliqués ou non dans l’exercice. Si l’effet de paramètres de l’exercice, comme l’intensité ou la durée, sur les changements neuroplastiques ont déjà été étudiés, l’effet du mode de contraction musculaire reste, quant à lui, moins connu. L’objectif de cette thèse a été d’évaluer les effets du mode de contraction musculaire sur les changements neuroplastiques consécutifs à un exercice locomoteur ou mono-articulaire. La première étude a montré que l’augmentation de l’excitabilité corticospinale d’un muscle non-impliqué dans l’exercice (muscle de la main), observée suite à un exercice de marche/ course, n’était pas modulée par le mode de contraction des muscles extenseurs du genou. En revanche, une modulation spécifique des réseaux intracorticaux par le mode de contraction impliqué lors d’un exercice a été mise en évidence par l’application d’un protocole de stimulation associative jumelée. Des observations similaires ont été faites dans une seconde étude investiguant les changements corticospinaux observés au niveau des muscles extenseurs du genou impliqués dans des exercices mono-articulaires fatigants, effectués dans un mode de contraction concentrique ou excentrique. Une troisième étude a montré que pour un exercice de marche/ course réalisé à même fréquence cardiaque en montée, à plat ou en descente, la modalité en descente induisait une fatigue musculaire des extenseurs du genou plus importante, avec des altérations contractiles plus marquée. La quatrième étude a montré que seule la modalité en descente induisait une augmentation de l’excitabilité corticospinale, et une réduction de l’inhibition corticale des muscles extenseurs du genou. Les travaux de cette thèse proposent que le mode de contraction musculaire lors d’un exercice n’est, en lui-même, pas un facteur prépondérant des changements neuroplastiques observés pour des muscles impliqués dans l’exercice. Ces changements neuroplastiques seraient au contraire dépendant de la magnitude de la fatigue neuromusculaire induite, elle-même dépendante du mode de contraction musculaire. / Along with cardiovascular and neuromuscular changes, mono-articular and locomotor exercises may induced neuroplastic changes from muscles involved, or non-involved, in the exercise. If the effect of exercise intensity or duration on neuroplastic changes has been previously investigated, the effect of the mode of muscle contraction remains unclear. The aim of this thesis was to investigate the effects of the mode of muscle contraction on neuroplastic changes induced a locomotor or a single-joint exercise. The first study showed that the increase in the corticospinal excitability of a non-exercised hand muscle, observed after a walking/ running exercise, was not modulated by the knee extensors mode of muscle contraction. However, a specific modulation of the intracortical networks by the mode of muscle contraction was evidenced using a paired-associative stimulation protocol. Similar findings were made in a second study that investigated corticospinal changes in the knee extensors following a fatiguing single-joint exercise, performed in either a concentric or an eccentric mode of muscle contraction. A third study showed that for a walking/ running exercise performed at the same heart rate in either a inline, a level or a decline condition, the latter condition induced a greater magnitude of neuromuscular fatigue of the knee extensors, with greater contractile impairments. The fourth study reported that only a decline exercise induced an increase in the corticospinal excitability, and a reduction of the cortical inhibition of the knee extensors. Altogether, findings from this thesis suggest that the mode of muscle contraction during an exercise is not, per se, a main factor responsible for neuroplastic changes observed in exercised muscles. Rather, these changes may depend upon the magnitude of neuromuscular fatigue induced, which could depend upon the mode of muscle contraction involved during exercise.
33

Motor Control and Perception during Haptic Sensing: Effects of Varying Attentional Demand, Stimuli and Age

Master, Sabah January 2012 (has links)
This thesis describes a series of experiments in human observers using neurophysiological and behavioural approaches to investigate the effects of varying haptic stimuli, attentional demand and age on motor control and perception during haptic sensing (i.e., using the hand to seek sensory information by touch). In Experiments I-IV, transcranial magnetic stimulation (TMS) was used to explore changes in corticomotor excitability when participants were actively engaged in haptic sensing tasks. These studies showed that corticospinal excitability, as reflected in motor evoked potential (MEP) amplitude, was greatly enhanced when participants were engaged in different forms of haptic sensing. Interestingly, this extra corticomotor facilitation was absent when participants performed finger movements without haptic sensing or when attention was diverted away from haptic input by a concurrent cognitive task (Exp I). This provided strong evidence that the observed corticomotor facilitation was likely central in origin and related to haptic attention. Neuroimaging has shown activation of the parieto-frontal network likely subserves this aspect of haptic perception. Further, this haptic-specific corticomotor facilitation was finely modulated depending on whether participants focused attention on identifying material (texture) as opposed to geometric properties of scanned surfaces (Exp II). With regards to aging effects, haptic-related corticomotor facilitation was associated with higher recognition accuracy in seniors (Exp III). In line with this, seniors exhibited similar levels of haptic-related corticomotor facilitation to young adults when task demands were adjusted for age (Exp IV). Interestingly, both young and senior adults also showed substantial corticomotor facilitation in the ‘resting’ hand when the ipsilateral hand was engaged in haptic sensing (Exp IV). Simply touching the stimulus without being required to identify its properties (no attentional task demands) produced no extra corticomotor facilitation in either hand or age group, attesting again to the specificity of the effects with regards to haptic attention. In Experiments V-VI, the ability to recognise 2-D letters by touch was investigated using kinematic and psychophysical measures. In Experiment V, we characterized how age affected contact forces deployed at the fingertip. This investigation showed that older adults exhibited lower normal force and increased letter-to-letter variability in normal force when compared to young adults. This difference in contact force likely contributed to longer contact times and lower recognition accuracy in older adults, suggesting a central contribution to age-related declines in haptic perception. Consistent with this interpretation, Experiment VI showed that haptic letter recognition in older adults was characterized not only by lower recognition accuracy but also by substantial increases in response times and specific patterns of confusion between letters. All in all, these investigations highlight the critical interaction of central factors such as attentional demand with aging effects on motor and perceptual aspects of haptic sensing. Of particular significance is the clear demonstration that corticomotor excitability is greatly enhanced when a haptic sensing component (i.e., attending to specific haptic features) is added to simple finger movements performed at minimal voluntary effort levels (typically <15 % of the maximal effort). These observations underline the therapeutic potential of active sensory training strategies based on haptic sensing tasks for the re-education of motor and perceptual deficits in hand function (e.g., subsequent to a stroke). The importance of adjusting attentional demands and stimuli is highlighted, particularly with regards to special considerations in the aging population.
34

Etude des atteintes de la substance blanche liées aux performances motrices et de langage des patients après un accident vasculaire cérébral / Study of white matter damage related to motor and speech performance of stroke patients

Vargas, Patricia 19 February 2014 (has links)
L'imagerie par tenseur de diffusion (DTI) est une technique qui permet d'étudier l'organisation et l'état structurel des faisceaux de substance blanche. L'étude de l'intégrité des faisceaux peut aider à comprendre et à déterminer la sévérité du pronostic des patients après un accident ischémique cérébral (AIC). Dans cette thèse, je présente deux études ; dans la première nous avons comparé les résultats obtenus à partir d'un template du faisceau Corticospinal (FCS) à ceux obtenus par la tractographie chez des sujets sains et des patients post-AIC. Dans les deux groupes, les valeurs de la fraction d'anisotropie (FA) obtenues avec la tractographie étaient plus élevées que celles du template. Cependant, chez les patients, les deux méthodes ont détecté une diminution des valeurs de FA du FCS ipsilésionnel, qui était corrélée aux scores moteurs, mais les valeurs de FA obtenues avec le template étaient mieux corrélées avec le signal BOLD généré par la main parétique. La deuxième étude cherchait à savoir si la sévérité de l'aphasie post-AIC pouvait être corrélée à l'atteinte de certaines régions de la substance blanche. L'analyse voxel à voxel a permis d'identifier une zone située à l'intersection des voies dorsale et ventrale du langage, au-dessous de la jonction temporo-pariétale (JTP) gauche. La gravité des dommages dans cette région, évaluée par les valeurs de la FA, était mieux corrélée aux déficits phasiques que le volume de l'infarctus. Dans cette thèse, nous avons trouvé que, après un AIC, l'atteinte du FCS est un bon prédicteur de la sévérité du déficit moteur et celle d'une région localisée au-dessous de la JTP gauche, est un bon prédicteur de la sévérité de l'aphasie. / The diffusion tensor imaging (DTI) is a technique used to study the organization and the structural state of white matter tracts. The study of the tracts integrity may help to understand and determine the severity of the patients? prognosis after an ischemic stroke. In this thesis, I present two studies: in the first we compared the results obtained from a template of the Corticospinal tract (CST) to those obtained by a tractography in healthy subjects and stroke patients. In both groups, the fractional anisotropy (FA) values obtained with the tractography were higher than those obtained by the template. However, in patients, both methods detected a decrease in FA values of the ipsilesional CST, which was correlated with motor scores, but the FA values obtained with the template were better correlated with the BOLD signal generated by the paretic hand. The second study investigated whether the severity of aphasia could be correlated to the damage of certain areas of the white matter. The voxel-based analysis identified an area at the intersection of the dorsal and ventral pathways of language, below the left temporo-parietal junction (JTP). The severity of the damage in this area, assessed by the FA values, was better correlated with the phasic deficits than the infarct volume. In this thesis, we found that after a stroke, the damage of the CST is a good predictor of the motor deficit severity and that of the region located below the left JTP is a good predictor of the aphasia severity.
35

Examining Neural Alterations as the Origins of Disability in Patients Following Anterior Cruciate Ligament Reconstruction

Lepley, Adam Scott 01 August 2014 (has links)
No description available.
36

In Vivo Visualization of Neural Pathways in the Rat Spinal Cord Using Viral Tracing

Keefe, Kathleen Mary January 2018 (has links)
Much of our understanding of the fascinating complexity of neuronal circuits comes from anatomical tracing studies that use dyes or fluorescent markers to highlight pathways that run through the brain and spinal cord. Viral vectors have been utilized by many previous groups as tools to highlight pathways or deliver transgenes to neuronal populations to stimulate growth after injury. In a series of studies, we explore anterograde and retrograde tracing with viral vectors to trace spinal pathways and explore their contribution to behavior in a rodent model. In a separate study, we explore the effect of stimulating intrinsic growth programs on regrowth of corticospinal tract (CST) axons after contusive injury. In the first study, we use self-complimentary adeno associated viral (scAAV) vectors to trace long descending tracts in the spinal cord. We demonstrate clear and bright labeling of cortico-, rubro- and reticulospinal pathways without the need for IH, and show that scAAV vectors transduce more efficiently than single stranded AAV (ssAAV) in neurons of both injured and uninjured animals. This study demonstrates the usefulness of these tracers in highlighting pathways descending from the brain. Retrograde tracing is also a key facet of neuroanatomical studies involving long distance projection neurons. In the next study, we highlight a lentivirus that permits highly efficient retrograde transport (HiRet) from synaptic terminals within the cervical and lumbar enlargements of the spinal cord. By injecting HiRet, we can clearly identify supraspinal and propriospinal circuits innervating MN pools relating to forelimb and hindlimb function. We observed robust labeling of propriospinal neurons, including high fidelity details of dendritic arbors and axon terminals seldom seen with chemical tracers. In addition, we examine changes in interneuronal circuits occurring after a thoracic contusion, highlighting populations that potentially contribute to spontaneous behavioral recovery in this lesion model. In a related study, we use a modified version of HiRet as part of a multi-vector system that synaptically silences neurons to explore the contribution of the rubrospinal tract (RST) and CST to forelimb motor behavior in an intact rat. This system employs Tetanus toxin at the neuronal synapse to prevent release of neurotransmitter via cleavage of vesicle docking proteins, effectively preventing the propagation of action potentials in those neurons. We find that shutdown of the RST has no effect on gross forelimb motor function in the intact state, and that shutdown of a small population of CST neurons in the FMC has a modest effect on grip strength. These studies demonstrate that the HiRet lentivirus is a unique tool for examining neuronal circuitry and its contribution to function. In the final study, we explore stimulation of the Phosphoinositide 3-kinase/Rac-alpha serine/threonine Protein Kinase (PI3K/AKT) growth pathway by antagonizing phosphatase and tensin homolog (PTEN), a major inhibitor, to encourage growth of CST axons after a contusive injury. We use systemic infusions of four distinct PTEN antagonist peptides (PAPs) targeted at different sites of the PTEN protein. We find robust axonal growth and sprouting caudal to a contusion in a subset of animals infused with PAPs targeted to the PTEN enzymatic pocket, including typical morphology of growing axons. Serotonergic fiber growth was unaffected by peptide infusion and did not correlate with CST fiber density. Though some variability was seen in the amount of growth within our animal groups, we find these PTEN antagonist peptides a promising and clinically relevant tool to encourage CST sprouting, and a potentially useful addition to therapies using combinatory strategies to enhance growth. These studies demonstrate that viral tracing is a powerful tool for mapping spinal pathways and elucidating their ability to reform spinal circuits after injury. Viral vectors can be used in both anterograde and retrograde tracing studies to highlight intricacies of neuronal cell bodies, axons and dendritic arbors with a high degree of fidelity. In the injured state, these tools can help identify pathways that contribute to spontaneous recovery of function by highlighting those that reform circuits past an injury site. In the uninjured state, these vectors can contain neuronal silencing methods that help define the contribution of specific pathways to behavior. / Neuroscience
37

Les interactions vestibulo-corticales qui sous-tendent le contrôle de la posture chez les sujets sains

Nepveu, Jean-François 02 1900 (has links)
Le système vestibulaire et le cortex moteur participent au contrôle de la posture, mais la nature de leurs interactions est peu documentée. Afin de caractériser les interactions vestibulo-corticales qui sous-tendent le contrôle de l’équilibre en position debout, l’activité électromyographique (EMG) du soléaire (SOL), du tibial antérieur (TA) et du péronier long (PERL) de la jambe droite a été enregistrée chez 14 sujets sains. La stimulation galvanique vestibulaire (GVS) a été appliquée avec la cathode derrière l’oreille droite ou gauche à différents intervalles inter-stimulus (ISIs) avant ou après la stimulation magnétique transcrânienne induisant des potentiels moteurs évoqués (MEPs) au niveau des muscles enregistrés. Lorsque que la cathode était à droite, une inhibition des MEPs a été observée au niveau du SOL à un ISI de 40 et 130 ms et une facilitation des MEPS a été observée au niveau TA à un ISI de 110 ms. Lorsque la cathode était à gauche, une facilitation des MEPs a été observée au niveau du SOL, du TA et du PERL à un ISI de 50, -10 et 0 ms respectivement. L’emplacement de ces interactions sur l’axe neural a été estimé en fonction des ISIs et en comparant l’effet de la GVS sur les MEPs à son effet sur l’EMG de base et sur le réflexe-H. Selon ces analyses, les modulations observées peuvent avoir lieu au niveau spinal ou au niveau supraspinal. Ces résultats suggèrent que les commandes de la voie corticospinale peuvent être modulées par le système vestibulaire à différents niveaux de l’axe neuronal. / The vestibular system and the motor cortex are involved in the control of posture but the nature of their interactions is poorly documented. To characterize vestibulo-cortical interactions underlying the control of balance during quiet standing, the electromyographic activity (EMG) of the soleus (SOL), tibialis anterior (TA) and peroneus longus (PERL) of the right leg was recorded in 14 healthy subjects. Bipolar galvanic vestibular stimulation (GVS) was applied with the cathode behind the right or left ear at various inter-stimulus intervals (ISI) before and after transcranial magnetic stimulation eliciting motor evoked potentials (MEP) in the muscles recorded. When the cathode was on the right, MEP in the SOL were inhibited at 40 and 130 ms while MEP were facilitated in TA at 110 ms. When the cathode was on the left, MEP were facilitated in the SOL at 50 ms, in TA at -10 ms and in PERL at 0 ms. The localization of these interactions along the neural axis was estimated according to the ISI and by comparing the effect of the GVS on the MEP to its effect on the background EMG and on the SOL H-reflex. Based on these analyses, the observed modulations of MEP observed could have occurred at spinal or supraspinal level. These results suggest that the corticospinal output may be modulated by the vestibular system at different levels of the neural axis.
38

Dégénérescence des neurones moteurs cortico-spinaux dans un modèle murin de sclérose latérale amyotrophique : dynamique spatio-temporelle et mécanismes moléculaires / Degeneration of corticospinal motor neurons in a mouse model of amyotrophic lateral sclerosis : spatio-temporal dynamics and molecular mechanisms

Marques, Christine 25 September 2017 (has links)
La sclérose latérale amyotrophique (SLA) se définit cliniquement par la dégénérescence combinée des neurones moteurs cortico-spinaux (NMCS) et des motoneurones bulbaires et spinaux (MnB et MnS). Quoique l’idée d’une origine corticale de la SLA soit de plus en plus considérée, la pathologie corticale, la dynamique spatio-temporelle de la dégénérescence des NMCS et les voies moléculaires impliquées restent peu connues. Ce travail de thèse a essentiellement cherché à pallier ce manque. Nous avons montré que chez les souris Sod1G86R, la perte des NMCS, qui semble se produire en l’absence de gliose réactionnelle majeure, se manifeste de manière somatotopique et précède l'apparition des symptômes moteurs et la dégénérescence des MnS. Nous avons purifié, grâce au développement d'un nouveau protocole, les NMCS adultes du cortex cérébral de souris saines ou malades à quatre stades de la maladie. L’analyse RNA-seq a permis d’identifier de nouveaux acteurs moléculaires précoces pouvant fournir une base pour le développement d'approches thérapeutiques fondées sur le maintien de NMCS sains et fonctionnels, et à long terme, à initier des stratégies thérapeutiques alternatives pour la SLA. / Amyotrophic lateral sclerosis (ALS) is clinically defined as the combined degeneration of the corticospinal motor neurons (CSMN) along with the bulbar and spinal motor neurons (BMN and SMN). While a growing body of evidence points to the cerebral cortex as the potential initiation site of ALS, little is known about the cortical pathology, the spatio-temporal dynamics of CSMN degeneration, and the molecular pathways involved. This thesis work aimed at filling this knowledge gap. In Sod1G86R, we showed that CSMN loss seems to take place without major gliosis, occurs in a somatotopic manner and precedes motor symptom appearance and SMN degeneration. We purified, thanks to the development of a novel protocol, adult CSMN from the cerebral cortex of healthy or diseased mice from early presymptomatic ages to the end stage of the disease. The RNA-seq analysis has made it possible to identify new and early molecular players in ALS. This would provide a foundation for the development of therapeutic approaches based on the maintenance of healthy and functional CSMN, and, on the long run, may in turn inform the development of alternative therapeutic strategies for ALS.
39

Adaptations fonctionnelles et nerveuses à l'entraînement par vibration locale : du sujet sain à la rééducation / FUNCTIONAL AND NEURAL ADAPTATIONS TO LOCAL VIBRATION TRAINING : FROM HEALTHY SUBJECTS TO REHABILITATION

Souron, Robin 08 December 2017 (has links)
La recherche de méthodes permettant de lutter contre le déconditionnement neuromusculaire à la suite par exemple d’une opération chirurgicale ou d’une immobilisation prolongée intéresse la communauté scientifique depuis de nombreuses années. Ce projet visait à proposer la technique de vibration locale (LV) comme une méthode alternative aux méthodes classiquement utilisées (e.g. vibration corps entier, stimulation électrique neuromusculaire) pour lutter contre ce déconditionnement neuromusculaire. Le premier objectif de ce travail de thèse était de déterminer les effets d’une application aigüe de LV sur la fonction neuromusculaire des muscles fléchisseurs dorsaux et extenseurs du genou de sujets sains. Nos résultats montrent une modulation de l’excitabilité du système nerveux central en réponse à l’application aigüe de LV, ce qui nous a permis d’envisager de potentielles adaptations si cette technique était utilisée de façon répétée sur plusieurs semaines. Ainsi, la seconde orientation de ce travail était d’évaluer les effets d’une application chronique (entraînement) de LV sur les propriétés fonctionnelles (force, hauteur de saut) et nerveuses (mesurées par stimulation magnétique transcrânienne) de sujets sains, jeunes et âgés. Nos résultats ont montré qu’un entraînement par LV était efficace pour améliorer les capacités fonctionnelles de ces deux populations, ces gains s’accompagnant d’adaptations nerveuses. Ces travaux nous ont alors conduits à la mise en place d’une dernière étude (en cours) à visée clinique, qui évaluait l’efficacité de LV en rééducation post-ligamentoplastie du ligament croisé antérieur du genou. / There is a need to find new methods to limit neuromuscular deconditioning that occurs after a surgery or prolonged immobilization. This thesis aimed to assess local vibration (LV) training as an alternative to methods classically used (e.g. whole body vibration, neuromuscular electrical stimulation) to fight against neuromuscular deconditioning. The first aim of this project was to determine the effects of a 30-min acute exposure to LV on the neuromuscular function of dorsiflexor and knee extensor muscles in a healthy population. Our results showed that acute LV intervention changed central nervous system excitability, allowing us to consider long-term adaptations to prolonged LV. Thus, the second aim of this thesis was to assess the effects of a chronic application (training) of LV on functional (maximal strength, squat jump performance) and neural (assessed with transcranial magnetic stimulation) properties of healthy young and old subjects. Our results showed that 4 to 8 weeks of LV increase functional capacities that were due to neural adaptations. Based on these results, an on-going study assessing the effectiveness of LV during a rehabilitation program for subjects who suffered from anterior cruciate ligament lesion has been proposed.
40

Effets aigus des étirements statiques et dynamiques sur le système neuromusculaire / Acute effects of static and dynamic stretching on the neuromuscular system

Opplert, Jules-Antoine 06 June 2019 (has links)
Dans un contexte de performance sportive, de réhabilitation ou de santé, les étirements sont couramment utilisés dans le but de préparer le système neuromusculaire à l’exercice subséquent. Si la littérature montre majoritairement que les étirements altèrent de façon aigue la performance musculaire et/ou fonctionnelle, il existe toutefois des études dont les résultats diffèrent, suggérant l’influence d’un certain nombre de facteurs sur la variabilité des réponses du système neuromusculaire. Pour une meilleure compréhension de cette variabilité et des mécanismes impliqués, cette thèse avait pour objectif d’examiner l’influence de différents paramètres sur le système neuromusculaire : la durée d’étirement, le groupe musculaire et la modalité d’étirement. Au travers de quatre études, il a été montré que les étirements statiques pouvaient altérer la production de force maximale et les propriétés neuromusculaires indépendamment de la durée d’étirement. Cependant, il est apparu que ces modulations étaient spécifiques au muscle, et plus précisément à la raideur relative du système musculo-tendineux. Indépendamment de la durée d’étirement, les étirements statiques ne seraient pas efficaces pour préparer le système neuromusculaire à une activité musculaire subséquente, et notamment pour des muscles raides. Plus particulièrement, les étirements dynamiques ne paraissent pas plus efficaces. Même si les effets néfastes ont été diminués comparativement aux étirements statiques, ils ne favoriseraient pas davantage la production de force ni la commande nerveuse. Toutefois, il est intéressant de noter qu’une durée courte d’étirements dynamiques peut réduire la résistance passive à l’étirement, et donc augmenter potentiellement l’amplitude articulaire maximale, sans affecter les capacités de production de force. Finalement, les étirements dynamiques pourraient être envisagés comme une activité musculaire dynamique, qui compense partiellement les effets néfastes de l’étirement sur la performance musculaire. D’un point de vue pratique, ceci suggère que ce type d’étirements peut être réalisé avant une performance, mais néanmoins accompagnés d’une activité musculaire de plus haute intensité, afin d’optimiser les effets de l’échauffement musculaire sur le système neuromusculaire. En définitive, la variabilité des réponses du système neuromusculaire serait dépendante de facteurs spécifiques, tels que la modalité d’étirement et la raideur relative du système musculo-tendineux, soulignant l’importance de les prendre en considération dans la pratique. / Stretching is traditionally incorporated into pre-exercise routines in health, rehabilitation and sporting environments to condition the neuromuscular system for exercise. While a large body of evidence reported that stretching may acutely impair the subsequent muscular performance, some conflicting results highlight possible mitigating factors of neuromuscular responses variability. Because the limited data available do not present a clear consensus, the aim of this thesis was to investigate the effects of different factors on neuromuscular responses to stretch: the muscle group, the stretch duration and modality. By means of four studies, it has been shown that static stretching may alter maximal voluntary torque and neuromuscular properties, irrespective of the stretch duration. However, these modulations were dependent on the muscle group, and more specifically on the intrinsic stiffness of the muscle-tendon system. Regardless of the stretch duration, static stretching appears to be not effective, or even detrimental, to prepare the musculotendinous system for subsequent exercises, and especially for stiff muscles. It is also relevant that dynamic stretching was not better than static stretching. Even if stretch-induced impairments were mitigated compared to static stretching, dynamic stretching would not optimize muscle strength capacities and central nervous system. However, a short duration of dynamic stretching may be sufficient to reduce passive resistive torque, and therefore potentially increase maximal range of motion, without affecting muscle strength capacities. Finally, dynamic stretching could be considered as dynamic muscle activity, which would partly counteract deleterious muscle-tendon stretching effects. From a practical point of view, dynamic stretching could be a part of warm-up procedure, but should be associated to stronger contractions to optimize the improvement in muscle strength capacities. In summary, the variability of neuromuscular responses to stretch would be dependent on specific factors, such as stretching modality and relative stiffness of the musculotendinous system, emphasizing the importance of taking it into consideration in practice.

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