Neural prostheses (NPs) are electronic stimulators that activate nerves to restore sensory or motor functions. Surface NPs are non-invasive and inexpensive, but are often poorly selective, activating non-targeted muscles and cutaneous sensory nerves that can cause pain or discomfort. Implanted NPs are highly selective, but invasive and costly. The stimulus router system (SRS) is a novel NP consisting of fully implanted leads that capture and route some of the current flowing between a pair of surface electrodes to the vicinity of a target nerve. One end of an SRS lead has a pick-up terminal that is implanted subcutaneously under the location of a surface electrode and the other end has a delivery terminal that is secured on or near the target nerve. The studies presented in this thesis address the development of the SRS from animal testing to its implementation as an upper extremity NP in a tetraplegic subject. Chapters 2 and 3 describe the SRSs basic properties, provide proof-of-principle of the system in animal studies and identify aspects that maximize its performance as a motor NP. The studies showed that selective and graded activation of deep-lying nerves can be achieved with the SRS over the full physiological range. Long term reliability of the system was demonstrated in chronic animal studies. The surface current needed to activate nerves with a SRS was found to depend on the proximity of the delivery terminal(s) to the target nerve, contact areas of the surface electrodes and implanted terminals, electrode configuration and the distances from the surface anode to the surface cathode and delivery terminal. Chapter 4 describes the first human proof-of-principle of the SRS during an intra-operative test. Finally, Chapter 5 describes the implementation of the SRS for restoration of hand function in a tetraplegic subject. Stimulation parameters and force elicited through the SRS, along with usage of the device were monitored up to 10 months after implantation. The system was found to be useful, reliable and robust. It is argued that the results of these studies indicate that the SRS provides the basis for a new family of NPs.

Introduction: The effect of electrical stimulation on muscle degeneration and regeneration is largely unknown and it has not been studied in conjunction with telomeres. The consumption of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread in athletes and the general population when faced with muscle soreness or injury. Furthermore, the effect of NSAIDs on muscle regeneration is controversial and its effect on telomere lengths is also unknown. Methods: Young adult males performed 200 electrically stimulated maximal isokinetic contractions with one leg (ES) and the other worked as a control (CON). They received either 1200mg ibuprofen (IBU) per day or placebo (PLA) from 21 days pre- to 30 days post-exercise. Muscle biopsies were obtained from the vastus lateralis of the CON leg at baseline (H0) and ES leg at 2.5h (H2.5) and both legs at 2, 7 and 30 days post-exercise. Blood samples were obtained at the same time points and at day 4 post-exercise. Afterwards the muscle and blood specimen were analysed for skeletal muscle and peripheral blood telomere lengths by Southern blot and signs of muscle degeneration and regeneration were quantified histologically. Results: Histological changes occurred in the ES leg, including; increased proportion of damaged myofibres (2.1±2.8%) and infiltrated myofibres (5.0±6.0%) at day 7, small myofibres (3.0±4.4%) and internally located myonuclei (2.9±3.1%) at day 30. The IBU group had significantly less internally located myonuclei at day 30 compared to PLA (1.7±2.4% vs. 4.1±3.8%). No significant differences were observed in skeletal muscle mean and minimum telomere lengths between ES and CON leg, between IBU and PLA group or between time points. Peripheral blood mean telomere lengths were not significantly different between IBU and PLA group, but between time points; H0 (9.6±1.2kb) and H2.5 (9.1±1.1kb) were significantly shorter than day 4 (10.3±1.6kb) and day 7 (10.1±1.5kb) (P<0.05). Conclusion: Electrically stimulated contractions caused significant muscle degeneration and regeneration in the 30 days post-exercise. Electrical stimulation also appeared to cause fluctuations in peripheral blood telomere lengths, but not skeletal muscle telomeres. The intake of ibuprofen appeared to interfere with muscle regeneration, but did not seem to affect the peripheral blood or skeletal muscle telomeres. However, due to marked individual variations and the small participant group it is difficult to conclude on the effects of electrical stimulation and ibuprofen on proliferative potential. Further studies are warranted to elucidate the effects of electrical stimulation and ibuprofen on blood and skeletal muscle telomeres.

More than one million people are living with spinal cord injury (SCI) in North America alone. Restoring lost motor function can alleviate SCI-related health problems, as well as markedly increase the quality of life enjoyed by individuals with SCI. Functional electrical stimulation (FES) can replace motor function in individuals with SCI by using short electrical pulses to generate contractions in paralyzed muscles. A wide range of FES applications have been proposed, but few application are actually available for community use by SCI consumers. A major factor contributing to this shortage of real-world FES applications is the lack of a feasible closed-loop control algorithm. The purpose of this thesis is to develop a closed-loop control algorithm that is suitable for use in practical FES applications. This thesis consists of three separate studies. The first study examined existing closed-loop control algorithms for FES applications, and showed that a method of testing FES control algorithms under realistic conditions is needed to evaluate their likely real-world performance. The second study provided such a testing method by developing a non-idealities block that can be used to modify the nominal response of electrically stimulated muscle in simulations of FES applications. Fatigue, muscle spasm, and tremor non-idealities are included in the block, which allows the user to specify the severity level for each type of non-ideal behaviour. This nonidealities block was tested in a simulation of electrically induced knee extension against gravity, and showed that the nominal performance of the controllers was substantially better than their performance in the realistic case that included the non-idealities model. The third study concerned the development and testing of a novel observer-based sliding mode control (SMC) algorithm that is suitable for use in real-world FES applications. This algorithm incorporated a fatigue minimization objective as well as co-contraction of the antagonist muscle group to cause the joint stiffness to track a desired value. The SMC algorithm was tested in a simulation of FES-based quiet standing, and the non-idealities block was used to determine the probable performance of the controller in the real world. This novel controller performed very well in simulation, and would be suitable for use in selected practical FES applications. The work contained in this thesis can easily be extended to a wide range of FES applications. This work represents a significant step forward in closed-loop control for FES applications, and will facilitate the development of sophisticated new electrical stimulation systems for use by consumers in their homes and communities.

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More than one million people are living with spinal cord injury (SCI) in North America alone. Restoring lost motor function can alleviate SCI-related health problems, as well as markedly increase the quality of life enjoyed by individuals with SCI. Functional electrical stimulation (FES) can replace motor function in individuals with SCI by using short electrical pulses to generate contractions in paralyzed muscles. A wide range of FES applications have been proposed, but few application are actually available for community use by SCI consumers. A major factor contributing to this shortage of real-world FES applications is the lack of a feasible closed-loop control algorithm. The purpose of this thesis is to develop a closed-loop control algorithm that is suitable for use in practical FES applications. This thesis consists of three separate studies. The first study examined existing closed-loop control algorithms for FES applications, and showed that a method of testing FES control algorithms under realistic conditions is needed to evaluate their likely real-world performance. The second study provided such a testing method by developing a non-idealities block that can be used to modify the nominal response of electrically stimulated muscle in simulations of FES applications. Fatigue, muscle spasm, and tremor non-idealities are included in the block, which allows the user to specify the severity level for each type of non-ideal behaviour. This nonidealities block was tested in a simulation of electrically induced knee extension against gravity, and showed that the nominal performance of the controllers was substantially better than their performance in the realistic case that included the non-idealities model. The third study concerned the development and testing of a novel observer-based sliding mode control (SMC) algorithm that is suitable for use in real-world FES applications. This algorithm incorporated a fatigue minimization objective as well as co-contraction of the antagonist muscle group to cause the joint stiffness to track a desired value. The SMC algorithm was tested in a simulation of FES-based quiet standing, and the non-idealities block was used to determine the probable performance of the controller in the real world. This novel controller performed very well in simulation, and would be suitable for use in selected practical FES applications. The work contained in this thesis can easily be extended to a wide range of FES applications. This work represents a significant step forward in closed-loop control for FES applications, and will facilitate the development of sophisticated new electrical stimulation systems for use by consumers in their homes and communities.

A forward dynamic model was developed to predict the performance of Spinal Cord Injured (SCI) individuals cycling an isokinetic ergometer using Neuromuscular Electrical Stimulation (NMES) to elicit contractions of the quadriceps, hamstring and gluteal muscles. Computer simulations were performed using three inter-connected models: a kinematic model of segmental linkages, a muscle model predicting forces in response to stimulation, and a kinetic model predicting ergometer pedal forces resulting from muscle stimulation. Specific model parameters for SCI individuals were determined through measurements from isometric and isokinetic contractions of the quadriceps muscles elicited using surface stimulation. The muscle model was fitted to data resulting from these isolated experiments in order to tailor the model's parameters to characteristics of muscles from SCI individuals. Isometric data from a range of knee angles were used to fit tendon slack lengths to the rectus femoris and vastus muscles. Adjustments to the quadriceps moment arm function were not able to improve the match between measured and modelled knee extension torques beyond those using moment arms taken from available literature. Similarly, literature values for constants from the muscle force - velocity relationship provided a satisfactory fit to the decline in torque with angular velocity, and parameter fitting did not improve this fit. Passive visco-elastic resistance remained constant for all velocities of extension except the highest (240 deg/s). Since knee angular velocities this high were not experienced during cycling, a visco-elastic dampener was not included within the present cycling model. The rise and fall in torque following NMES onset and cessation were used to fit constants to match the rate of change in torque. Constants for the rise in torque following NMES onset were significantly altered by changes in knee angle, with more extended angles taking longer for torque to rise. This effect was small, however, within the range of angles used during cycling, and consequently was not included within the cycling model. The decline in torque after NMES cessation was not affected by knee angle. A period of five minutes cyclical isometric activity of the quadriceps resulted in torque declining by more than 75% from rested levels. The activation time constants were largely unaffected by this fatigue, however, with only a small increase in the time for torque to decline, and no change in rise time or the delay between stimulation changes and resulting torque changes. The cycling model, therefore, did not incorporate any effect for changes in activation timing with fatigue. Performance of the full model was evaluated through measurements taken from SCI individuals cycling a constant velocity ergometer using NMES elicited contractions of the quadriceps, hamstring and gluteal muscles. Pedal transducers measured forces applied to the pedals for comparison between measured and modelled values. A five minute period of continuous cycling using just the quadriceps muscles produced similar results to those found for isolated knee extension. External power output dropped by 50% over the five-minute period, however there was no change in the pattern of torque production with fatigue. Cycling experiments were conducted using single muscle groups across a range of NMES firing angles. Experimental protocols were designed to seek the firing angles for each muscle that maximised power output by that group. Changes in power output in response to firing angle changes were not large, however, in comparison to the effects of cumulative fatigue and inconsistent power output between trials. This lead to large uncertainties in the determination of those firing angles that maximised power output by each muscle. Results suggest that NMES firing angles to maximise power output by the quadriceps muscles were relatively similar for each subject. For the hamstring muscles, however, substantial differences were observed in the range of firing angles that maximised power output. Results for the gluteal muscles were variable, with some subjects not applying any measurable torque to the cranks, even with maximal stimulation applied. The model produced a good match to experimental data for the quadriceps muscles, both in the shape of pedal force curves and the firing angles that maximised external power output. The individual variability in hamstring responses was not, however, predicted by the model. Modification of the relative size of the hamstrings' moment arms about the hip and knee substantially improved the match between measured and modelled data. Analysis of results suggests that individual variability in the relative size of these moment arms is a major cause of variation in individual's response to hamstring stimulation. There were apparent limitations in the model's ability to predict the shape of crank torques resulting from stimulation of the gluteus maximus muscle. It is suggested that further research be conducted to enable modelling of this muscle using a range of fibre lengths and moment arms.

No description available.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-02-14T13:16:34Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE_Isis Suruagy Correia Moura FINAL BIBLIOTECA_com ficha PRONTA.pdf: 1497533 bytes, checksum: 117972a8d3ac5d94cef2fa68b971f285 (MD5) / Made available in DSpace on 2017-02-14T13:16:34Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE_Isis Suruagy Correia Moura FINAL BIBLIOTECA_com ficha PRONTA.pdf: 1497533 bytes, checksum: 117972a8d3ac5d94cef2fa68b971f285 (MD5) Previous issue date: 2015-11-17 / Estudos recentes têm desafiado o paradigma atual da fisiologia do exercício, onde os mecanismos que determinam a tolerância ao exercício estão relacionados a aspectos dos sistemas cardiovascular, respiratório, metabólico e mecanismos neuromusculares, passando a enfatizar o papel crucial desempenhado pelo cérebro na regulação do desempenho no exercício. Assim, a estimulação cerebral não-invasiva, como por exemplo, a estimulação transcraniana por corrente contínua (ETCC) vem sendo utilizada para aprimorar o desempenho e a tolerância ao exercício físico. Embora os resultados desta associação sejam considerados promissores, poucos estudos, até o momento, avaliaram a associação da ETCC com o exercício físico dinâmico. Esta tese apresenta dois artigos originais realizados com o propósito de promover o progresso na pesquisa da associação entre a ETCC e a excitabilidade cortical com o exercício físico. O primeiro estudo foi realizado para investigar os efeitos de diferentes intensidades de exercício na excitabilidade corticoespinal em exercício dinâmico. Nesta pesquisa, 18 indivíduos saudáveis participaram de um estudo crossover com três diferentes protocolos de exercícios em cicloergômetro: (i) 10 min a 75% Wmax (intensidade alta); (ii) 15 min a 60% Wmáx (intensidade moderada) ou (iii) 30 min a 45% Wmáx (intensidade baixa). A sessão controle foi feita com indivíduos em repouso. A excitabilidade cortical foi avaliada pela estimulação magnética transcraniana (EMT). Os resultados deste estudo são apresentados no artigo intitulado " Intensity-dependent effects of physical exercise on corticospinal excitability in healthy humans: a pilot study ", os resultados sugerem que a diminuição da excitabilidade corticoespinal foi encontrada apenas na sessão de exercício de intensidade alta. O segundo estudo foi realizado a fim de investigar se a ETCC, no córtex motor (M1) ou córtex temporal esquerdo (T3), melhoram a tolerância ao exercício e verificar os efeitos da ETCC na excitabilidade cortical de indivíduos saudáveis não atletas. Os resultados deste estudo são apresentados no artigo intitulado: " Does tDCS might be effective to improve physical performance and attenuate effort perception during maximal dynamic exercise in non-athletes? ". Os resultados apontam que a ETCC não foi eficaz em melhorar o desempenho em exercício dinâmico máximo, todavia a ETCC anódica aplicada na área motora da perna (M1) pode aumentar a excitabilidade cortical de indivíduos saudáveis. / Contemporary’studies have challenged the current paradigm of exercise physiology, where mechanisms determining exercise tolerance have focused on the cardiovascular, respiratory, metabolic and neuromuscular mechanisms, by emphasising the crucial role played by the brain in the regulation of exercise performance. Thus, non-invasive brain stimulation, as for exemple, transcranial direct current stimulation (tDCS) has recently been used to improve performance and tolerance to physical exercise. Although, the results from this associations could be promising, a few studies are reported with association of tDCS with dynamic exercise. This thesis presents two original articles conducted with the purpose of progress in the researching of the association of tDCS and excitability cortical with physical exercise. The first study was done in order to investigate effects of different intensities of locomotor exercise on corticospinal excitability. In this study, 18 healthy subjects participated in a crossover design study of three different exercise protocols on a cycle ergometer: (i) 10 min at 75% Wmax (high intensity); (ii) 15min at 60% Wmax (moderate intensity) or (iii) 30 min at 45% Wmax (low intensity). A control session was done with subjects at rest. Cortical excitability was evaluated trough transcranial magnetic stimulation (TMS). The results of this study are shown in the article entitled “Intensity-dependent effects of physical exercise on corticospinal excitability in healthy humans: a pilot study” and the results suggest that decrease in corticospinal excitability was found only in the session of exercise of high intensity. The second study was performed in order to determine whether tDCS, in motor cortex (M1) or left temporal cortex (T3), improve exercise tolerance in healthy non-athlete subjects and verify the effects of tDCS on cortical excitability of healthy subjects. The results of this study are shown in the article titled: Does tDCS might be effective to improve physical performance and attenuate effort perception during maximal dynamic exercise in nonathletes?. The results pointed out that tDCS is not be effective to improve performance in maximal dynamic exercise, but anodal tDCS in M1 might increase cortical excitability in lower limbs motor cortex.