A functional electrical stimulation system for human walking inspired by reflexive control principles

This study presents an innovative multichannel functional electrical stimulation gait-assist system which employs a well-established purely reflexive control algorithm, previously tested in a series of bipedal walking robots. In these robots, ground contact information was used to activate motors in the legs, generating a gait cycle similar to that of humans. Rather than developing a sophisticated closed-loop functional electrical stimulation control strategy for stepping, we have instead utilised our simple reflexive model where muscle activation is induced through transfer functions which translate sensory signals, predominantly ground contact information, into motor actions. The functionality of the functional electrical stimulation system was tested by analysis of the gait function of seven healthy volunteers during functional electrical stimulation–assisted treadmill walking compared to unassisted walking. The results demonstrated that the system was successful in synchronising muscle activation throughout the gait cycle and was able to promote functional hip and ankle movements. Overall, the study demonstrates the potential of human-inspired robotic systems in the design of assistive devices for bipedal walking

Neuroprosthetic Technologies to Evaluate and Train Leg Motor Control in Neurologically Impaired Individuals

Spinal cord injury (SCI) disrupts many essential sensorimotor and autonomic functions. Consequently, individuals with SCI can face decades with permanent disabilities. Advances in clinical management have decreased morbidity, but no clinical trial has yet demonstrated the efficacy of a repair strategy. In the past decade, Courtine lab has developed neurotechnologies that restored volitional control of locomotion in animal models of SCI. The intervention acts over two-time windows. In the short-term, the delivery of epidural electrical stimulation (EES) targeting the posterior lumbar roots with timing that mimics the natural activation of the spinal cord enables stepping in otherwise paralyzed rats. In the long-term, this targeted EES with intensive robot-assisted overground training triggers a reorganization of descending pathways that reestablished voluntary control of the paralyzed legs, even without EES. These results in animal models encouraged the transfer of these technologies and concepts to clinical applications. My contribution to this translational research program forms the core of my thesis. The first section presents a software that I developed in order to enable a comprehensive yet semi-automated analysis of kinematics and muscle activity underlying locomotor functions in humans. This toolbox allows to evaluate gait features of people with neuromotor deficits, quantify locomotor performance compared to healthy people or to monitor changes in different experimental conditions or over the time course of interventions, and automatically generate comprehensive gait reports directly understandable by scientists and clinicians. The second section introduces a paradigm shift in robotic postural assistance: the gravity-assist. We demonstrated the detrimental impact of high levels of body weight support on gravity-dependent interactions during standing and walking. We developed a gravity-assist algorithm that fine-tunes the forward and upward body weight support to reestablish these interactions based on each patientâs residual capacities. We validated the personalized gravity-assist in 30 individuals with SCI or stroke. Compared to other conditions of support, the gravity-assist enabled all the patients to improve their locomotion performance. This platform establishes refined conditions to empower and train overground locomotion in a safe yet ecological environment. The third section reports the development of targeted EES in patients with chronic SCI, and the impact of an intensive 5-month rehabilitation with gravity-assist and targeted EES on the recovery of motor functions. The key findings can be summarized as follows: We established procedures to configure targeted EES that immediately enabled voluntary control of weak or paralyzed muscles; Targeted EES boosts the residual supraspinal inputs to the lumbar spinal cord, enabling all the patients to adapt their gait to specific tasks; Locomotor performance improved during the rehabilitation; All the patients regained voluntary control over previously paralyzed muscles without EES. These combined results establish the proof-of-concept on the therapeutic potential of targeted EES and intensive, robot-assisted rehabilitation to restore locomotion after SCI. Together with similar results obtained in the US in patients with severe SCI, our findings are establishing a pathway towards the development of a viable treatment to support motor functions and improve recovery after SCI

A Systematic Review Establishing the Current State-of-the-Art, the Limitations, and the DESIRED Checklist in Studies of Direct Neural Interfacing With Robotic Gait Devices in Stroke Rehabilitation

Background: Stroke is a disease with a high associated disability burden. Robotic-assisted gait training offers an opportunity for the practice intensity levels associated with good functional walking outcomes in this population. Neural interfacing technology, electroencephalography (EEG), or electromyography (EMG) can offer new strategies for robotic gait re-education after a stroke by promoting more active engagement in movement intent and/or neurophysiological feedback. Objectives: This study identifies the current state-of-the-art and the limitations in direct neural interfacing with robotic gait devices in stroke rehabilitation. Methods: A pre-registered systematic review was conducted using standardized search operators that included the presence of stroke and robotic gait training and neural biosignals (EMG and/or EEG) and was not limited by study type. Results: From a total of 8,899 papers identified, 13 articles were considered for the final selection. Only five of the 13 studies received a strong or moderate quality rating as a clinical study. Three studies recorded EEG activity during robotic gait, two of which used EEG for BCI purposes. While demonstrating utility for decoding kinematic and EMG-related gait data, no EEG study has been identified to close the loop between robot and human. Twelve of the studies recorded EMG activity during or after robotic walking, primarily as an outcome measure. One study used multisource information fusion from EMG, joint angle, and force to modify robotic commands in real time, with higher error rates observed during active movement. A novel study identified used EMG data during robotic gait to derive the optimal, individualized robot-driven step trajectory. Conclusions: Wide heterogeneity in the reporting and the purpose of neurobiosignal use during robotic gait training after a stroke exists. Neural interfacing with robotic gait after a stroke demonstrates promise as a future field of study. However, as a nascent area, direct neural interfacing with robotic gait after a stroke would benefit from a more standardized protocol for biosignal collection and processing and for robotic deployment. Appropriate reporting for clinical studies of this nature is also required with respect to the study type and the participants' characteristics

Brain-controlled cycling system for rehabilitation following paraplegia with delay-time prediction

Objective: Robotic rehabilitation systems have been investigated to assist with motor dysfunction recovery in patients with lower-extremity paralysis caused by central nervous system lesions. These systems are intended to provide appropriate sensory feedback associated with locomotion. Appropriate feedback is thought to cause synchronous neuron firing, resulting in the recovery of function. Approach: In this study, we designed and evaluated an ergometric cycling wheelchair, with a brain-machine interface (BMI), that can force the legs to move by including normal stepping speeds and quick responses. Experiments were conducted in five healthy subjects and one patient with spinal cord injury (SCI), who experienced the complete paralysis of the lower limbs. Event-related desynchronization (ERD) in the β band (18‐28 Hz) was used to detect lower-limb motor images. Main results: An ergometer-based BMI system was able to safely and easily force patients to perform leg movements, at a rate of approximately 1.6 seconds/step (19 rpm), with an online accuracy rate of 73.1% for the SCI participant. Mean detection time from the cue to pedaling onset was 0.83±0.31 s Significance: This system can easily and safely maintain a normal walking speed during the experiment and be designed to accommodate the expected delay between the intentional onset and physical movement, to achieve rehabilitation effects for each participant. Similar BMI systems, implemented with rehabilitation systems, may be applicable to a wide range of patients

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease

People with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD

Spinal Cord Injury and Transcutaneous Spinal Cord Stimulation

Recent research of epidural and transcutaneous electrical spinal cord stimulation has demonstrated unprecedented improvements in motor function thought to be irreversibly lost due to chronic, severe spinal cord injury. Studies in parallel assess these methods for spasticity management as an alternative to medications that are often accompanied by deleterious side effects. As a noninvasive intervention, transcutaneous spinal cord stimulation holds the great potential to find its way into wide clinical application. Its firm establishment and lasting acceptance as clinical practice in spinal cord injury will not only hinge on the demonstration of safety and efficacy, but also on the delineation of a conceptual framework of the underlying physiological mechanisms. This will also require advancing our understanding of immediate and temporary effects of transcutaneous spinal cord on neuronal circuits in the intact and injured spinal cord. The purpose of this collection of papers is to bring together peers in the field to share—and eventually fuse—their pertinent research into current neurorehabilitation practice by providing a clinical perspective and novel insights into the underlying mechanisms

A biomechanical investigation of seated balance and upright mobility with a robotic exoskeleton in individuals with a spinal cord injury

Spinal cord injury (SCI) is a complex medical condition with multiple sequelae. The level and severity of a lesion will determine the degree of disability and associated co- morbidities, the most obvious of which is paralysis. Other concomitant issues, such as muscle contractures, poor seated posture and fear of falling, can also lead to a reduced quality of life. Although there is currently no cure for SCI, many of the comorbidities can be managed or mitigated through technology and physical rehabilitation practices.The aim of this thesis was to inform spinal cord injury (SCI) mobility rehabilitation, focusing on postural control and upright stepping using robotic assisted gait training (RAGT). A systematic review investigating RAGT use in SCI concluded that although RAGT has the potential to benefit upright locomotion of SCI individuals, it should not replace other therapies but should be incorporated into a multi-modality rehabilitation approach.Seated postural control, upper-body posture and fear-of-falling in SCI individuals were also explored. Stability performance and control demand were compared between high- and low-level injury groups as was fear-of-falling. An individualised limit of stability boundary (LOS) facilitated the differentiation between high- and low-level injuries during static tasks; however, its use during dynamic tasks was limited and potentially influenced by fear-of-falling.Few studies have quantified the user’s motion inside a lower limb robotic exoskeleton (LEXO), and none have reported marker placement repeatability. Standard error of measurement was reported for three-dimensional trunk and pelvic orientations and hip, knee and ankle angles in the sagittal plane during level walking. This revealed the marker set and placement to produce good levels of agreement between visits, with most values falling between the accepted standard of 2-5o. These findings indicated that the marker placement was repeatable and could be used in the subsequent chapters involving motion capture of overground walking.Three-dimensional gait parameters of able-bodied individuals walking with and without a LEXO at two speeds (comfortable (CMBL) and speed-matched (SLOW) to the LEXO) were investigated. Statistical parametric mapping revealed significantly different waveforms at the ANOVA level for all kinematic variables, however minimal differences in sagittal plane lower limb kinematics were identified between LEXO and SLOW gait, suggesting LEXO gait resembled slow walking when speed-matched. Altered kinematics of the pelvis and trunk during LEXO use suggest that overground exoskeletons may provide a training environment benefiting postural control training.Finally, the biomechanical characteristics of able-bodied and SCI users walking in an overground LEXO were investigated. Variables associated with neuroplasticity in SCI (hip extension and lower limb un-loading) were not significantly different between groups, indicating that afferent stimuli to facilitate neuroplastic adaptations in individuals with a SCI can be generated during LEXO gait. Upper-body orientation facilitated stepping and maintained balance, thereby requiring the participant’s active involvement.This thesis has provided evidence that LEXOs can deliver appropriate stimuli for upright stepping and that upper-body engagement can facilitate postural control training, potentially leading to improved seated postural control

Functional Resistance Training During Walking: Design, Testing, and Evaluation of Passive and Semi-Passive Wearable Devices for Providing Targeted Resistance to the Leg During Gait

Injuries to the neuromusculoskeletal systems often result in muscle weakness, abnormal coordination strategies, and gait impairments. Functional resistance training during walking—where a patient walks while a device increases loading on the leg—is an emerging approach to combat these symptoms. While simple passive devices (i.e., ankle weights and resistance bands) can be applied for this training, rehabilitation robots have more potential upside because they can be controlled to treat multiple gait abnormalities and can be monitored by clinicians. However, the cost of conventional robotic devices limits their use in the clinical or home setting. Hence, in this dissertation, we designed, developed, and tested passive and semi-passive wearable exoskeleton devices as low-cost solutions for providing controllable/configurable functional resistance training during walking. We developed and tested two passive exoskeleton devices for providing resistance to walking and tested their effects on able-bodied participants and stroke survivors. First, we created a patented device that used a passive magnetic brake to provide a viscous (i.e., velocity-dependent) resistance to the knee. The resistive properties of the device could be placed under computer control (i.e., made semi-passive) to control resistance in real-time. Next, we created a passive exoskeleton that provided an elastic (i.e., position-dependent) resistance. While not controllable, this device was highly configurable. Meaning it could be used to provide resistance to joint flexion, extension, or to both (i.e., bidirectionally). Human subjects testing with these devices indicated they increased lower-extremity joint moments, powers, and muscle activation during training. Training also resulted in significant aftereffects—a potential indicator of therapeutic effectiveness—once the resistance was removed. A separate experiment indicated that individuals often kinematically slack (i.e., reduce joint excursions to minimize effort) when resistance is added to the limb. We also found that providing visual feedback of joint angles during training significantly increased muscle activation and kinematic aftereffects (i.e., reduced slacking). With passive devices, the type of passive element used largely dictates the muscle groups, types of muscle contraction, joint actions, and the phases of gait when a device is able to apply resistance. To examine this issue, we compared the training effects of viscous and elastic devices that provided bidirectional resistance to the knee during gait. Additionally, we compared training with viscous resistances at the hip and knee joints. While the resistance type and targeted joint altered moments, powers, and muscle activation patterns, these methods did not differ in their ability to produce aftereffects, alter neural excitability, or induce fatigue in the leg muscles. While this may indicate that the resistance type does not have a large effect on functional resistance training during walking, it is possible that an extended training with these devices could produce a different result. Lastly, we used musculoskeletal modeling in OpenSim to directly compare several strategies that have been used to provide functional resistance training to gait in the clinic or laboratory setting. We found that devices differed in their ability to alter gait parameters during walking. Hence, these findings could help clinicians when selecting a resistive strategy for their patients, or engineers when designing new devices or control schemes. Collectively, this dissertation introduces a new class of wearable devices for functional resistance training during walking and establishes the biomechanical and neurophysiological effects and the clinical potential of these devices in able-bodied and stroke survivors.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169867/1/epwiv_1.pd

A Computational Approach for the Design of Epidural Electrical Spinal Cord Stimulation Strategies to Enable Locomotion after Spinal Cord Injury

Spinal cord injury (SCI) is a major cause of paralysis with currently no effective treatment. Epidural electrical stimulation (EES) of the lumbar spinal cord has been shown to restore locomotion in animal models of SCI, but has not yet reached the same level of efficacy in humans. The mechanisms through which EES promotes locomotion, and the causes underlying these inter-species differences remain largely unknown, although essential to fully exploit the therapeutic potential of this neuromodulation strategy. Here, we addressed these questions using a deductive approach based on computer simulations and hypothesis-driven experiments, and proposed complementary strategies to enhance the current efficacy of EES-based therapies. In the first part of this thesis, we studied the mechanisms through which EES enables locomotion in rat models of SCI. Performing simulations and behavioral experiments, we provided evidence that EES modulates proprioceptive afferents activity, without interfering with the ongoing sensory signals. We showed that this synergistic interaction allows muscle spindle feedback circuits to steer the unspecific excitation delivered by EES to functionally relevant pathways, thus allowing the formation of locomotor patterns. By leveraging this understanding, we developed a stimulation strategy that allowed adjusting lesion-specific gait deficits, hence increasing the therapeutic efficacy of EES. In the second part of this thesis, we evaluated the influence of trunk posture on proprioceptive feedback circuits during locomotion, and thus on the effect of EES, in rat models of SCI. By combining modeling and experiments, we showed that trunk orientation regulates leg proprioceptive signals, as well as the motor patterns produced during EES-induced stepping. We exploited these results to develop a control policy that by automatically regulating trunk orientation significantly enhanced locomotor performance. In the last part of this thesis, we investigated the causes underlying species-specific effects of EES. Hypothesis-driven simulations suggested that in humans continuous EES blocks the proprioceptive signals traveling along the recruited fibers. We corroborated this prediction by performing experiments in rats and people with SCI. In particular, we showed that EES disrupts the conscious perception of leg movements, as well as the afferent modulation of sensorimotor circuits in humans, but not in rats. We provide evidence that in humans, due to this phenomenon, continuous EES can only facilitate locomotion to a limited extent. This was insufficient to provide clinically relevant improvements in the tested participants. Finally, we proposed two sensory-compliant stimulation strategies that might overcome these limitations, and thus augment the therapeutic efficacy of EES. In this thesis we elucidated key mechanisms through which EES promotes locomotion, we exposed critical limitations of continuous EES strategies when applied to humans, and we introduced complementary strategies to maximize the efficacy of EES therapies. These findings have far-reaching implications in the development of future strategies and technologies supporting the recovery of locomotion in people with SCI using EES