Evaluating Neuromuscular Function of the Biceps Brachii after Spinal Cord Injury: Assessment of Voluntary Activation and Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) or peripherally (VAPNS) to reveal what levels of the nervous system are disrupting the innervation of muscle fibers. Voluntary activation measured with TMS (VATMS) can indicate deficits in voluntary cortical drive to innervate muscle. However, measurement of VATMS is limited by technical challenges, including the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its antagonist (i.e. MEP ratio) may be an important parameter in the assessment of VATMS. Using current methodology, VATMS cannot be reliably assessed in patient populations including individuals with tetraplegia. The overall purpose of this work was to investigate novel TMS-based methods to evaluate neuromuscular function after spinal cord injury. First, we developed and evaluated new methodology to assess VATMS in individuals with tetraplegia. The objective of the first study was to optimize the biceps/triceps MEP ratio using modulation of isometric elbow flexion angle in nonimpaired participants and participants with tetraplegia following cervical SCI (C5-C6). We hypothesized that the more flexed elbow angle would increase the MEP ratio. The MEP ratio was only modulated in the nonimpaired group but not across the entire range of voluntary efforts used to estimate VATMS. However, we established that VATMS and VAPNS in individuals with tetraplegia were repeatable across days. In a second study, we aimed to optimize MEPs during the assessment of VATMS using paired pulse TMS to elicit intracortical facilitation and short-interval intracortical inhibition. We hypothesized that intracortical facilitation would lead to an increased MEP ratio compared to single pulse and that short-interval intracortical inhibition would lead to a lower MEP ratio. The MEP ratio was modulated in both groups but not across the entire range of voluntary efforts, and did not affect VATMS estimation compared to single pulse TMS. Paired pulse TMS outcomes revealed abnormal patterns of intracortical inhibition in individuals with tetraplegia. Further, VATMS was sensitive to the linearity of the voluntary moment and superimposed twitch relationship. Linearity was lower in SCI relative to nonimpaired participants. We discuss the limitations of VATMS in assessing neuromuscular impairments in tetraplegia. In a third study, we aimed to collect MEP input-output curves of the biceps in SCI and nonimpaired and evaluate curve-fitting methodology as well as their repeatability across sessions. We hypothesized that slopes would be greater in the SCI group compared to nonimpaired. Slopes obtained with linear regression were greater in tetraplegia compared to nonimpaired participants, suggesting compensatory reorganization of corticomotor pathways after SCI. Linear regression accurately represented the slope of the modeled data compared to sigmoidal function curve-fitting method. Slopes were also found to be repeatable across days in both groups. In a fourth study, we aimed to implement a low-cost navigated TMS system (\u3c $3000) that uses motion tracking, 3D printed parts and open-source software to monitor coil placement during stimulation. We hypothesized that using this system would improve coil position and orientation consistency and decrease MEP variability compared to the conventional method when targeting the biceps at rest and during voluntary contractions across two sessions in nonimpaired participants. Coil orientation error was reduced but the improvement did not translate to lower MEP variability. This low-cost approach is an alternative to expensive systems in tracking the motor hotspot between sessions and quantifying the error in coil placement when delivering TMS. Finally, we conclude and recommend future research directions to address the challenges that we identified during this work to improve our ability to monitor neuromuscular impairments and contribute to the development of more effective neurorehabilitation strategies

Development of a hybrid assist-as-need hand exoskeleton for stroke rehabilitation.

Stroke is one of the leading causes of disability globally and can significantly impair a patient’s ability to function on a daily basis. Through physical rehabilitative measures a patient may regain a level of functional independence. However, required therapy dosages are often not met. Rehabilitation is typically implemented through manual one-to-one assistance with a physiotherapist, which quickly becomes labour intensive and costly. Hybrid application of functional electrical stimulation (FES) and robotic support can access the physiological benefits of direct muscle activation while providing controlled and repeatable motion assistance. Furthermore, patient engagement can be heightened through the integration of a volitional intent measure, such as electromyography (EMG). Current hybrid hand-exoskeletons have demonstrated that a balanced hybrid support profile can alleviate FES intensity and motor torque requirements, whilst improving reference tracking errors. However, these support profiles remain fixed and patient fatigue is not addressed. The aim of this thesis was to develop a proof-of-concept assist-as-need hybrid exoskeleton for post-stroke hand rehabilitation, with fatigue monitoring to guide the balance of support modalities. The device required the development and integration of a constant current (CC) stimulator, stimulus-resistant EMG device, and hand-exoskeleton. The hand exoskeleton in this work was formed from a parametric Watt I linkage model that adapts to different finger sizes. Each linkage was optimised with respect to angular precision and compactness using Differential Evolution (DE). The exoskeleton’s output trajectory was shown to be sensitive to parameter variation, potentially caused by finger measurement error and shifts in coupler placement. However, in a set of cylindrical grasping trials it was observed that a range of movement strategies could be employed towards a successful grasp. As there are many possible trajectories that result in a successful grasp, it was deduced that the exoskeleton can still provide functional assistance despite its sensitivity to parameter variation. The CC stimulator developed in this work has a part cost of USD $145 and allows flexible adjustment of waveform parameters through an on-board micro-controller. The device is designed to output current up to ±30mA given a voltage compliance of ±50V. When applied across a 2kΩ load, the device exhibited a linear output transfer function, with a maximum ramp tracking error of 5 The stimulus-resistant EMG device builds on current designs by using a novel Schmitt trigger based artefact detection channel to adaptively blank stimulation artefacts without stimulator synchronisation. The design has a part cost of USD$150 and has been made open-source. The device demonstrated its ability to record EMG over its predominant energy spectrum during stimulation, through the stimulation electrodes or through separate electrodes. Pearson’s correlation coefficients greater than 0.84 were identified be- tween the normalised spectra of volitional EMG (vEMG) estimates during stimulation and of stimulation-free EMG recordings. This spectral similarity permits future research into applications such as spectral-based monitoring of fatigue and muscle coherence, posing an advantage over current same-electrode stimulation and recording systems, which can- not sample the lower end of the EMG spectrum due to elevated high-pass filter cut-off frequencies. The stimulus-resistant EMG device was used to investigate elicited EMG (eEMG)-based fatigue metrics during vEMG-controlled stimulation and hybrid support profiles. During intermittent vEMG-controlled stimulation, the eEMG peak-to-peak amplitude (PTP) index was the median frequency (MDF) had a negative correlation for all subjects with R > 0:62 during stimulation-induced wrist flexion and R > 0:55 during stimulation-induced finger flexion. During hybrid FES-robotic support trials, a 40% reduction in stimulus intensity resulted in an average 21% reduction in MDF gradient magnitudes. This reflects lower levels of fatigue during the hybrid support profile and indicates that the MDF gradient can provide useful information on the progression of muscle fatigue. A hybrid exoskeleton system was formed through the integration of the CC stimulator, stimulus-resistant EMG device, and the hand exoskeleton developed in this work. The system provided assist-as-need functional grasp assistance through stimulation and robotic components, governed by the user’s vEMG. The hybrid support profile demonstrated consistent motion assistance with lowered stimulation intensities, which in-turn lowered the subjects’ perceived levels of fatigue

Down-Conditioning of Soleus Reflex Activity using Mechanical Stimuli and EMG Biofeedback

Spasticity is a common syndrome caused by various brain and neural injuries, which can severely impair walking ability and functional independence. To improve functional independence, conditioning protocols are available aimed at reducing spasticity by facilitating spinal neuroplasticity. This down-conditioning can be performed using different types of stimuli, electrical or mechanical, and reflex activity measures, EMG or impedance, used as biofeedback variable. Still, current results on effectiveness of these conditioning protocols are incomplete, making comparisons difficult. We aimed to show the within-session task- dependent and across-session long-term adaptation of a conditioning protocol based on mechanical stimuli and EMG biofeedback. However, in contrast to literature, preliminary results show that subjects were unable to successfully obtain task-dependent modulation of their soleus short-latency stretch reflex magnitude

Development of a hybrid robotic system based on an adaptive and associative assistance for rehabilitation of reaching movement after stroke

Stroke causes irreversible neurological damage. Depending on the location and the size of this brain injury, different body functions could result affected. One of the most common consequences is motor impairments. The level of motor impairment affectation varies between post-stroke subjects, but often, it hampers the execution of most activities of daily living. Consequently, the quality of life of the stroke population is severely decreased. The rehabilitation of the upper-limb motor functions has gained special attention in the scientific community due the poor reported prognosis of post-stroke patients for recovering normal upper-extremity function after standard rehabilitation therapy. Driven by the advance of technology and the design of new rehabilitation methods, the use of robot devices, functional electrical stimulation and brain-computer interfaces as a neuromodulation system is proposed as a novel and promising rehabilitation tools. Although the uses of these technologies present potential benefits with respect to standard rehabilitation methods, there still are some milestones to be addressed for the consolidation of these methods and techniques in clinical settings. Mentioned evidences reflect the motivation for this dissertation. This thesis presents the development and validation of a hybrid robotic system based on an adaptive and associative assistance for rehabilitation of reaching movements in post-stroke subjects. The hybrid concept refers the combined use of robotic devices with functional electrical stimulation. Adaptive feature states a tailored assistance according to the users’ motor residual capabilities, while the associative term denotes a precise pairing between the users’ motor intent and the peripheral hybrid assistance. The development of the hybrid platform comprised the following tasks: 1. The identification of the current challenges for hybrid robotic system, considering twofold perspectives: technological and clinical. The hybrid systems submitted in literature were critically reviewed for such purpose. These identified features will lead the subsequent development and method framed in this work. 2. The development and validation of a hybrid robotic system, combining a mechanical exoskeleton with functional electrical stimulation to assist the execution of functional reaching movements. Several subsystems are integrated within the hybrid platform, which interact each other to cooperatively complement the rehabilitation task. Complementary, the implementation of a controller based on functional electrical stimulation to dynamically adjust the level of assistance is addressed. The controller is conceived to tackle one of the main limitations when using electrical stimulation, i.e. the highly nonlinear and time-varying muscle response. An experimental procedure was conducted with healthy and post-stroke patients to corroborate the technical feasibility and the usability evaluation of the system. 3. The implementation of an associative strategy within the hybrid platform. Three different strategies based on electroencephalography and electromyography signals were analytically compared. The main idea is to provide a precise temporal association between the hybrid assistance delivered at the periphery (arm muscles) and the users’ own intention to move and to configure a feasible clinical setup to be use in real rehabilitation scenarios. 4. Carry out a comprehensive pilot clinical intervention considering a small cohort of patient with post-stroke patients to evaluate the different proposed concepts and assess the feasibility of using the hybrid system in rehabilitation settings. In summary, the works here presented prove the feasibility of using the hybrid robotic system as a rehabilitative tool with post-stroke subjects. Moreover, it is demonstrated the adaptive controller is able to adjust the level of assistance to achieve successful tracking movement with the affected arm. Remarkably, the accurate association in time between motor cortex activation, represented through the motor-related cortical potential measured with electroencephalography, and the supplied hybrid assistance during the execution of functional (multidegree of freedom) reaching movement facilitate distributed cortical plasticity. These results encourage the validation of the overall hybrid concept in a large clinical trial including an increased number of patients with a control group, in order to achieve more robust clinical results and confirm the presented herein.Programa Oficial de Doctorado en Ingeniería Eléctrica, Electrónica y AutomáticaPresidente: Ramón Ceres Ruiz.- Secretario: Luis Enrique Moreno Lorente.- Vocal: Antonio Olivier

Doctor of Philosophy

dissertationParalysis due to spinal cord injury or stroke can leave a person with intact peripheral nerves and muscles, but deficient volitional motor control, thereby reducing their health and quality of life. Functional neuromuscular stimulation (FNS) has been widely studied and employed in clinical devices to aid and restore lost or deficient motor function. Strong, selective, and fatigue-resistant muscle forces can be evoked by asynchronously stimulating small independent groups of motor neurons via multiple intrafascicular electrodes on an implanted Utah slanted electrode array (USEA). Determining the parameters of asynchronous intrafascicular multi-electrode stimulation (aIFMS), i.e., the per-electrode stimulus intensities and the interelectrode stimulus phasing, to evoke precise muscle force or joint motion presents unique challenges because this system has multiple-inputs, the n independently stimulated electrodes, but only one measurable output, the evoked endpoint isometric force or joint position. This dissertation presents three studies towards developing robust real-time control of aIFMS. The first study developed an adaptive feedforward algorithm for selecting aIFMS per-electrode stimulus intensities and interelectrode stimulus phasing to evoke a variety of isometric ankle plantar-flexion force trajectories. In simulation and experiments, desired step, sinusoidal, and more-complex time-varying isometric forces were successfully evoked. The second study developed a closed-loop feedback control method for determining aIFMS per-electrode stimulus intensities to evoke precise single-muscle isometric ankle plantar-flexion force trajectories, in real-time. Using a proportional closed-loop force-feedback controller, desired step, sinusoid, and more complex time-varying forces were evoked with good response characteristics, even in the presence of nonlinear system dynamics, such as muscle fatigue. The third study adapted and extended the closed-loop feedback controller to the more demanding task of controlling joint position in the presence of opposing joint torques. A proportional-plus-velocity-plus-integral (PIV) joint-angle feedback controller evoked and held desired steps in position with responses th a t were stable, consistent, and robust to disturbances. The controller evoked smooth ramp-up (concentric) and ramp-down (eccentric) motion, as well as precise slow moving sinusoidal motion. The control methods developed in this dissertation provide a foundation for new lower-limb FNS-based neuroprostheses that can generate sustained and coordinated muscle forces and joint motions that will be desired by paralyzed individuals on a daily basis. proportional-plus-velocity-plus-integral (PIV) joint-angle feedback controller evoked and held desired steps in position with responses th a t were stable, consistent, and robust to disturbances. The controller evoked smooth ramp-up (concentric) and ramp-down (eccentric) motion, as well as precise slow moving sinusoidal motion. The control methods developed in this dissertation provide a foundation for new lower-limb FNS-based neuroprostheses that can generate sustained and coordinated muscle forces and joint motions that will be desired by paralyzed individuals on a daily basis

Postural control and adaptation to threats to balance stability

Postural control is the ability to maintain equilibrium and orientation in a gravitational environment. It is dependent on feedback and feedforward mechanisms that generate appropriate corrective movement based on body-sway motion detected primarily by visual, vestibular, and proprioceptive sensory systems. Since information from the various senses is not always accurate (e.g. by disease) or available (e.g. with eyes closed), the postural control system must adapt to maintain stance. This thesis aimed to investigate postural control and adaptation to threats of balance. Effective approaches for the clinical measurement of postural control still remains to be developed. In the past, it has been common to investigate patients’ balance by having them stand upon compliant foam blocks with eyes open and closed since standing on foam is believed to affect the accuracy of information from cutaneous mechanoreceptors on the soles of the feet. However, when assessing balance on foam blocks with different compliances and mechanical properties, it was found that postural sway was larger on firmer compliant surfaces, which also increased the importance of visual information. Postural adaptation was also investigated by repeatedly perturbing balance using muscle vibrations. In healthy, young persons, a slow adaptive change was observed. This adaptation involved decreased costs of standing including decreased energy, body movement and muscle activity and changes to the relationship between muscle activity and movement. The characteristics of the adaptation also depended on the availability of visual information. The elderly had poor postural control with and without being perturbed but were able to adapt to improve their poor balance. However, decreased mechanoreceptive sensation in the elderly prevented them from adapting their balance to the level of younger test subjects. Sleep deprivation decreased attention and alertness and resulted in decreased postural control and adaptation. The findings in this thesis extend what is known about motor learning. The adaptive learning capability of the postural control system, and hence the accurate reconstruction of the kinematics and kinetics of movement, was dependant on ones own mechanoreceptive somatosensation and availability of visual information. Decreasing attention and alertness through sleep deprivation decreased adaptive capabilities, suggesting an important role for sleep in memory and consolidation of a new motor skill