Dans le contexte du handicap, certaines solutions technologiques permettent de pallier des déficiences pour lesquelles la pharmacologie et la chirurgie sont impuissantes. Les neuroprothèses font partie de ces solutions technologiques. Il s'agit de dispositifs s'interfaçant avec le système nerveux (périphérique ou central), soit pour agir sur celui-ci (stimulation électrique fonctionnelle par exemple), soit pour y recueillir des signaux destinés à commander un dispositif extérieur tel qu'une prothèse robotisée.Le travail présenté dans ce manuscrit s'inscrit dans ce second contexte du recueil de signaux neuronaux sur un nerf périphérique. Aujourd'hui, le seul dispositif utilisable de manière chronique sur l'être humain est l'électrode Cuff tripolaire. Celle-ci recueille l'activité globale du nerf et manque singulièrement de sélectivité. Des dispositifs plus sélectifs, comme les électrodes intrafasciculaires, existent, mais présentent l'inconvénient d'être traumatisants pour le nerf et extrêmement délicats à mettre en place. Notre objectif, au cours de ce travail de thèse, a donc été de développer un dispositif associant la sélectivité d'une électrode intrafasciculaire à la faible invasivité d'une électrode Cuff.Nous avons donc commencé par étudier, en simulation, le potentiel d'action extracellulaire d'un axone myélinisé. Nos simulations nous ont permis de mettre en évidence un "phénomène local", évoqué dans plusieurs publications d'expérimentations antérieures à nos travaux et propre aux axones myélinisés, décroissant très rapidement quand augmente la distance de l'axone à l'électrode. Nous avons donc étudié et dimensionné un dispositif simple, spécifiquement sensible à ce phénomène local.A partir de ce dispositif, nous avons proposé une architecture d'électrode extraneurale qui possède un indice de sélectivité très supérieur à celui de la plus sélective des électrodes extraneurales publiées à ce jour.Malheureusement, ce gain en sélectivité se paie par une dégradation du rapport signal sur bruit. Nous avons donc étudié les solutions permettant de réduire le niveau de bruit ramené au niveau de l'électrode, et nous exposons les grandes lignes d'un dispositif électronique d'acquisition multi-voie faible bruit à température ambiante.Enfin, nous avons construit un modèle d'axone artificiel qui nous a permis de valider expérimentalement nos modèles de simulation ainsi que l'existence du phénomène local. / In the context of sensory or motor deficiencies, some technologic solutions can be proposed in case pharmacology and surgery are inefficient. Neuroprostheses are one of these technologic solutions. It consists in devices interfacing the (peripheral or central) nervous system, either acting on it (functional electric stimulation, neuromodulation...), or recording neuro-signals (automated prosthesis control, closed-loop stimulation...).The work presented in this manuscript focuses on the latter, and more precisely, on recording neuro-signals from peripheral nerves. Today, the only implantable device that can be used for chronic recording on human peripheral nervous system is the tripolar cuff electrode.Unfortunately, it is sensitive to the nerve global activity and exhibits a very low selectivity. More selective devices, like intrafascicular electrodes, exist, but has the drawback to be more traumatizing for the nerve.Therefore, the objective of this thesis was to develop a device associating the selectivity of intrafascicular electrode together with the low invasivity of cuff electrode.We thus started to perform simulations of the extracellular action potential of myelinated axons, putting in evidence a "local phenomenon", already described in some previous publications, and decreasing very quickly with the distance. Then, we have designed and studied a simple neural interface based on the characteristics of this local phenomenon, and specifically sensitive to it.The results have allowed us to propose an extraneural electrode, promising a selectivity index far higher than today's state of the art.Unfortunately, the gain in selectivity leads also to the degradation of signal-to-noise ratio. We have thus studied solutions to reduce noise at the electrode interface, and presented the architecture of a low-noise multi-channel acquisition circuit fitting our requirements.Finally, we have built the artificial model of an axon in order to experimentally validate simulation results, as well as the the local phenomenon characteristics.

Trunk instability is a major problem for people with spinal cord injury (SCI); it not only limits their independence, but also leads to secondary health complications such as kyphosis, pressure sores, and respiratory dysfunction. In exploring mechanisms that may facilitate or compromise postural stability, dynamic models are very useful because the spine dynamics are difficult to study in vivo compared to other structures of the body. Therefore, one objective of this work was to develop a detailed three-dimensional dynamic model of the human trunk as a tool for investigating the neural-mechanical control strategy that healthy people apply to maintain trunk stability during various tasks. Since trunk control is fairly complex, however, another objective of this work was to provide insights into the balance control strategy of a simpler neuro-musculo-skeletal system that may facilitate future studies on trunk control. For this purpose, the control of the ankle joint complex during quiet standing (anterior-posterior degree of freedom) was studied in place of the trunk. The obtained results reveal that a neural-mechanical control scheme using a proportional-derivative controller as the neural control strategy can overcome a large sensory-motor (feedback) time delay and stabilize the ankle joint during quiet standing. Moreover, a detailed dynamic model of the trunk has been developed that is: (1) based on highly accurate geometric models; and (2) universally applicable. Thus, this work also responds to the postulation that structurally more complex models are needed to better characterize the biomechanics of multifaceted systems. Combining the developed biomechanical tools for the trunk with the postural control insights for the ankle joint during standing will be beneficial for: (1) understanding the neural-mechanical control strategy that facilitates trunk stability in healthy people; and for (2) developing neuroprostheses for trunk stability after SCI and other neurological disorders.

Trunk instability is a major problem for people with spinal cord injury (SCI); it not only limits their independence, but also leads to secondary health complications such as kyphosis, pressure sores, and respiratory dysfunction. In exploring mechanisms that may facilitate or compromise postural stability, dynamic models are very useful because the spine dynamics are difficult to study in vivo compared to other structures of the body. Therefore, one objective of this work was to develop a detailed three-dimensional dynamic model of the human trunk as a tool for investigating the neural-mechanical control strategy that healthy people apply to maintain trunk stability during various tasks. Since trunk control is fairly complex, however, another objective of this work was to provide insights into the balance control strategy of a simpler neuro-musculo-skeletal system that may facilitate future studies on trunk control. For this purpose, the control of the ankle joint complex during quiet standing (anterior-posterior degree of freedom) was studied in place of the trunk. The obtained results reveal that a neural-mechanical control scheme using a proportional-derivative controller as the neural control strategy can overcome a large sensory-motor (feedback) time delay and stabilize the ankle joint during quiet standing. Moreover, a detailed dynamic model of the trunk has been developed that is: (1) based on highly accurate geometric models; and (2) universally applicable. Thus, this work also responds to the postulation that structurally more complex models are needed to better characterize the biomechanics of multifaceted systems. Combining the developed biomechanical tools for the trunk with the postural control insights for the ankle joint during standing will be beneficial for: (1) understanding the neural-mechanical control strategy that facilitates trunk stability in healthy people; and for (2) developing neuroprostheses for trunk stability after SCI and other neurological disorders.

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Les Interfaces Cerveau-Machine assurent une connexion bidirectionnelle entre un patient et son environnement. Un patient atteint de déficience motrice lourde peut, au moyen d'un dispositif implanté dans son cerveau, commander des objets connectés par la seule action de son activité cérébrale. Une des premières exigences que cela requiert est de concevoir un implant, dit neuroprothèse, susceptible de rester implanté de façon chronique. L’utilisation des micro-nano-technologies permet de fabriquer une neuroprothèse qui réponde aux exigences d’un tel dispositif : performant, fiable et limitant la réaction de rejet par l’organisme. Pour cela, l’implant est conçu sur un substrat flexible à base de polymère biocompatible. La souplesse de l’implant lui permet de mieux s’adapter aux tissus cérébraux et d’assurer un contact intime avec les neurones en diminuant la réaction inflammatoire. Cet implant est inséré au moyen d’un support rigide biodégradable issu de la fibroïne de soie. Des premiers tests sur culture in vitro et sur petit animal (souris) ont montré des résultats prometteurs en termes de biocompatibilité et biostabilité sur le court et moyen terme. / Brain-Computer Interfaces ensure a bidirectional connection between a patient and his environment. Using an implant in his brain, a patient suffering from severe motor deficiency can control external devices through the sole action of his cerebral activity. One of the major requirements for such application is to conceive an implant, also called neuroprosthesis, that is able to be implanted for long periods of time.Micro-nano-technology enable the fabrication of a neuroprosthesis that gives in the demands of such item: efficient, reliable and limiting body rejection mechanisms. To that aim, the implant is designed on a flexible substrate provided by a biocompatible polymer. Implant flexibility allows for better compliance with the brain tissues and insures a more intimate contact with the neurons while maintaining minimal inflammation. This implant is inserted in the brain using a bioresorbable support made of silk fibroin. First tests in vitro on culture cells, and in vivo on mice showed promising results in terms of biocompatibility and biostability in the short and medium term.

La stimulation électrique fonctionnelle (FES) est présente depuis des décennies dans les centres de rééducation. Le principe de cette technique est de créer une dépolarisation de la membrane (potentiel d’action) des cellules excitables (axones ou myocytes) entrainant une contraction musculaire. Employée dans la plupart des cas pour le renforcement musculaire et la prévention des atrophies musculaires faisant suite à une lésion de la moelle épinière, la FES peut également être utilisée pour diminuer la spasticité et restaurer des mouvements des membres. Ainsi, certains dispositifs (neuroprothèses) utilisant la FES sont utilisés depuis plus de 25 ans, pour permettre à certains patients atteints de paralysies des membres supérieurs de pouvoir effectuer des préhensions. Les patients gagnent alors en autonomie dans les activités de la vie quotidienne ce qui limite leurs recours aux aides humaines. Cependant, bien que ce type de neuroprothèse se présente comme l’une des techniques les plus prometteuses pour le rétablissement de la fonction de préhension chez des sujets atteints d’une lésion de la moelle épinière, son utilisation reste limitée. En effet, les dispositifs de stimulation externe provoque des mouvements peu précis et les modes de pilote de cette stimulation, peu ergonomiques, ne sont pas accessibles à la plupart des patients lésés médullaires. Ces difficultés sont atténuées lorsque la stimulation est implantée et le mode de contrôle adapté à la pathologie. Parmi les dispositifs implantées, tous utilisent la stimulation des points moteurs pour rétablir des mouvements de main ce qui nécessite l’implantation de nombreuses électrodes et donc une opération chirurgicale lourde. Des complications liées aux matériels implantés peuvent apparaître au cours du temps. Ce travail de thèse propose une approche originale basée sur (i) la stimulation sélective nerveuse (à l’aide d’une électrode gouttière multi contact) pour rétablir des mouvements de préhension chez des patients tétraplégiques et (ii) l’utilisation de signaux émanant de muscles supra lésionnels pour le contrôle de cette stimulation. Des expérimentations humaines et animales réalisées en conditions aiguës ont démontré la faisabilité de notre approche. Ainsi, la stimulation du nerf sciatique par notre électrode gouttière a permis d’activer sélectivement plusieurs muscles antagonistes chez les 5 animaux de l’étude inclus dans l’étude. Une sélectivité intra fasciculaire est retrouvée chez 3 des 5 animaux. La stimulation du nerf médian chez un patient tétraplégique a permis d’activer sélectivement les muscles palmaris longuset flexor carpi radialis. Concernant le contrôle de la neuroprothèse, nous avons mis en évidence chez les 5 sujets tétraplégiques ayant participé aux expérimentations, une combinaison de muscles pouvant être utilisée pour piloter facilement un dispositif. Des contractions continues ou gradées de ces muscles peuvent être maintenues et ce, sans aucun apprentissage ou entrainement préalable. Les modalités de contrôle et les muscles préférentiels sont patient-dépendant. / Functional electrical stimulation (FES) is used for decades in rehabilitation centers. The principle of this technique is to create a membrane depolarization (action potential) of excitable cells (myocytes or axons) to cause a muscle contraction. Used in most cases for muscle strengthening and prevention of muscle atrophy following a spinal cord injury, FES can also be used to reduce spasticity and restore limb movement. For example, some devices (neuroprostheses) using FES are used for over 25 years, to allow some patients with paralysis of the upper limbs to perform hand movements. Patients then becoming more independent in activities of daily living which limits their use of human aid. However, although this type of neuroprosthesis stands as one of the most promising techniques for the recovery of the gripping function in subjects with spinal cord injury, its use is limited. Indeed, external stimulation devices cause imprecise movements and modes of control modes, not very ergonomic, are not accessible to most spinal cord injured patients. These difficulties are alleviated when the stimulation is implanted and control mode adapted to the pathology. Among the implanted devices all use the stimulation of motor pointsto restore hand movements which requires the implantation of many electrodes and therefore a major surgery. Complications related to the implanted materials can occur over time. This thesis proposes an original approach based on (i) selective nerve stimulation (using a multi contact cuff electrode) to restore gripping motion in tetraplegic patients and (ii) use of signals from supra lesional muscles to control this stimulation. Human and animal experimentations performed in acute conditions have demonstrated the feasibility of our approach. Thus, stimulation of the sciatic nerve by our cuff electrode allowed to selectively activate several antagonistic muscles in the 5 animals included in the study. Intra fascicular selectivity was found in 3 of 5 animals. The stimulation of the median nerve of a tetraplegic patient allowed to selectively activate the palmaris longus and flexor carpi radialis muscles. For the control of neuroprosthesis we demonstrated in the 5 tetraplegics subjects who participated in the experiments, a combination of muscles that can be used to easily control a device. Continuous or graded contractions of these muscles can be maintained, without any prior learning or training. The control modalities and preferential muscles are patient-dependent.

<p>Spinal cord injury (SCI) and other neurological diseases and disorders can cause urinary dysfunction that can cause serious health problems and reduce an individual's quality of life. Current methods for treating urinary dysfunction have major limitations or provide inadequate improvement in urinary symptoms. Pudendal nerve stimulation is a potential means of restoring control of bladder function in persons with neurological disease or spinal cord injury. Bladder contraction and relaxation can be evoked by pudendal afferent stimulation, and peripheral pudendal afferent branches may be ideal targets for a bladder control neural prosthesis. This dissertation investigates control of bladder function by selective activation of pudendal afferents.</p> <p>This study investigated the ability to improve both urinary continence and micturition by both direct and minimally-invasive electrical stimulation of selected pudendal afferents in &#945;-chloralose anesthetized male cats. Direct stimulation of the pudendal afferents in the dorsal nerve of the penis (DNP), percutaneous DNP stimulation, and intraurethral stimulation were used to investigate the bladder response to selective activation of pudendal afferents. Finite element modeling of the cat lower urinary tract was used to investigate the impact of intraurethral stimulation location and intraurethral electrode configuration on activation of pudendal afferents. Also, the impact of pharmacological and surgical block of sympathetic activity to the bladder on the bladder reflexes evoked by DNP stimulation was investigated to determine the role of the sympathetic bladder innervation on the mechanism of bladder activation by pudendal afferent stimulation.</p> <p>The DNP is an ideal target for restoring urinary function because stimulation at low frequencies (5-10 Hz) improves urinary continence, while stimulation at high frequencies (33-40 Hz) improves urinary voiding. Intraurethral stimulation is a valid method for clinical investigation of the ability to evoke bladder inhibition and activation via selective activation of the DNP or cranial sensory branch (CSN) of the pudendal nerve. In the cat, intraurethral stimulation can activate the bladder via two distinct neural pathways, a supraspinal pathway reflex activated by the CSN and a spinal reflex activated by the DNP. Finite element modeling revealed the importance of urethral location for selective pudendal afferent activation by intraurethral stimulation. Finally, the sympathetic bladder pathway does not play a significant role in the mechanism mediating bladder activation by DNP stimulation. These findings imply that selective pudendal afferent stimulation is a promising approach for restoring control of bladder function to individuals with SCI or other neurological disorders.</p> / Dissertation

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomesare modest, infrared neural stimulation (INS) was applied to the cochlear nucleus in a ratanimal model. Pulsed INS, delivered to the surface of the cochlear nucleus via an opticalfibre, evoked auditory brainstem responses (ABR) and generated broad neural activation inthe inferior Colliculus (IC). Varying the parameters of the laser stimulation revealed laserpeak power to be the dominating parameter for both ABR and IC responses. Strongestresponses were recorded when the fibre was placed at lateral positions on the cochlearnucleus, close to the temporal bone. After deafening by auditory nerve section, ABR andIC responses to INS disappeared, consistent with a reported "optophonic" effect, a laser-inducedacoustic artifact. Thus, for deaf individuals who use the auditory brainstemimplant, INS alone does not appear promising as a new approach.