First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction.

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

Modulation of spinal circuits following phase-dependent electrical stimulation of afferent pathways.

Objective.Peripheral electrical stimulation (PES) of afferent pathways is a tool commonly used to induce neural adaptations in some neural disorders such as pathological tremor or stroke. However, the neuromodulatory effects of stimulation interventions synchronized with physiological activity (closed-loop strategies) have been scarcely researched in the upper-limb. Here, the short-term spinal effects of a 20-minute stimulation protocol where afferent pathways were stimulated with a closed-loop strategy named selective and adaptive timely stimulation (SATS) were explored in 11 healthy subjects.Approach. SATS was applied to the radial nerve in-phase (INP) or out-of-phase (OOP) with respect to the muscle activity of the extensor carpi radialis (ECR). The neural adaptations at the spinal cord level were assessed for the flexor carpi radialis (FCR) by measuring disynaptic Group I inhibition, Ia presynaptic inhibition, Ib facilitation from the H-reflex and estimation of the neural drive before, immediately after, and 30 minutes after the intervention.Main results.SATS strategy delivered electrical stimulation synchronized with the real-time muscle activity measured, with an average delay of 17 ± 8 ms. SATS-INP induced increased disynaptic Group I inhibition (77 ± 23% of baseline conditioned FCR H-reflex), while SATS-OOP elicited the opposite effect (125 ± 46% of baseline conditioned FCR H-reflex). Some of the subjects maintained the changes after 30 minutes. No other significant changes were found for the rest of measurements.Significance.These results suggest that the short-term modulatory effects of phase-dependent PES occur at specific targeted spinal pathways for the wrist muscles in healthy individuals. Importantly, timely recruitment of afferent pathways synchronized with specific muscle activity is a fundamental principle that shall be considered when tailoring PES protocols to modulate specific neural circuits. (NCT number 04501133).

Benchmarking the Effects on Human-Exoskeleton Interaction of Trajectory, Admittance and EMG-Triggered Exoskeleton Movement Control.

Nowadays, robotic technology for gait training is becoming a common tool in rehabilitation hospitals. However, its effectiveness is still controversial. Traditional control strategies do not adequately integrate human intention and interaction and little is known regarding the impact of exoskeleton control strategies on muscle coordination, physical effort, and user acceptance. In this article, we benchmarked three types of exoskeleton control strategies in a sample of seven healthy volunteers: trajectory assistance (TC), compliant assistance (AC), and compliant assistance with EMG-Onset stepping control (OC), which allows the user to decide when to take a step during the walking cycle. This exploratory study was conducted within the EUROBENCH project facility. Experimental procedures and data analysis were conducted following EUROBENCH's protocols. Specifically, exoskeleton kinematics, muscle activation, heart and breathing rates, skin conductance, as well as user-perceived effort were analyzed. Our results show that the OC controller showed robust performance in detecting stepping intention even using a corrupt EMG acquisition channel. The AC and OC controllers resulted in similar kinematic alterations compared to the TC controller. Muscle synergies remained similar to the synergies found in the literature, although some changes in muscle contribution were found, as well as an overall increase in agonist-antagonist co-contraction. The OC condition led to the decreased mean duration of activation of synergies. These differences were not reflected in the overall physiological impact of walking or subjective perception. We conclude that, although the AC and OC walking conditions allowed the users to modulate their walking pattern, the application of these two controllers did not translate into significant changes in the overall physiological cost of walking nor the perceived experience of use. Nonetheless, results suggest that both AC and OC controllers are potentially interesting approaches that can be explored as gait rehabilitation tools. Furthermore, the INTENTION project is, to our knowledge, the first study to benchmark the effects on human-exoskeleton interaction of three different exoskeleton controllers, including a new EMG-based controller designed by us and never tested in previous studies, which has made it possible to provide valuable third-party feedback on the use of the EUROBENCH facility and testbed, enriching the apprenticeship of the project consortium and contributing to the scientific community.

Neurorobotics and neuroprostheses: Towards a new anatomy.

The idea of this Special Issue arose from the technological advances in bionic, robotic, and neural rehabilitation systems and the common need to comprehend in detail how human anatomical structures can be replicated or controlled. Motor control theories, among others, include the generalized control program theory, the equilibrium point hypothesis, or the optimal control approach in which neural commands to the muscles are a result of the central nervous system solving an optimization problem for a specific cost function. No matter the alternative interpretation selected to replicate biological control of human movements, artificial "anatomies" should consider not only motor capabilities from the central nervous system but integrate bioinspired mechanical features (such as compliance) in artificial limbs. The development of wearable robotics and neuroprosthetic systems for human movement compensation and control is naturally inspired by human anatomy and biology. Cutting-edge technological advances in the field of biomedical and neural engineering are bringing us more and more close to a new artificial anatomy with which humans could augment their motor capabilities or replace them after they are compromised. Either augmentative/assistive or rehabilitation technologies in the near future will require engineering solutions based on novel approaches to create usable neurorobotic and neuroprosthetic systems for the most relevant societal needs.

Prediction of Pathological Tremor Signals Using Long Short-Term Memory Neural Networks.

Previous implementations of closed-loop peripheral electrical stimulation (PES) strategies have provided evidence about the effect of the stimulation timing on tremor reduction. However, these strategies have used traditional signal processing techniques that only consider phase prediction and might not model the non-stationary behavior of tremor. Here, we tested the use of long short-term memory (LSTM) neural networks to predict tremor signals using kinematic data recorded from Essential Tremor (ET) patients. A dataset comprising wrist flexion-extension data from 12 ET patients was pre-processed to feed the predictors. A total of 180 models resulting from the combination of network (neurons and layers of the LSTM networks, length of the input sequence and prediction horizon) and training parameters (learning rate) were trained, validated and tested. Predicted tremor signals using LSTM-based models presented high correlation values (from 0.709 to 0.998) with the expected values, with a phase delay between the predicted and real signals below 15 ms, which corresponds approximately to 7.5% of a tremor cycle. The prediction horizon was the parameter with a higher impact on the prediction performance. The proposed LSTM-based models were capable of predicting both phase and amplitude of tremor signals outperforming results from previous studies (32--56% decreased phase prediction error compared to the out-of-phase method), which might provide a more robust PES-based closed-loop control applied to PES-based tremor reduction.

Intramuscular EMG-Driven Musculoskeletal Modelling: Towards Implanted Muscle Interfacing in Spinal Cord Injury Patients.

OBJECTIVE: Surface EMG-driven modelling has been proposed as a means to control assistive devices by estimating joint torques. Implanted EMG sensors have several advantages over wearable sensors but provide a more localized information on muscle activity, which may impact torque estimates. Here, we tested and compared the use of surface and intramuscular EMG measurements for the estimation of required assistive joint torques using EMG driven modelling. METHODS: Four healthy subjects and three incomplete spinal cord injury (SCI) patients performed walking trials at varying speeds. Motion capture marker trajectories, surface and intramuscular EMG, and ground reaction forces were measured concurrently. Subject-specific musculoskeletal models were developed for all subjects, and inverse dynamics analysis was performed for all individual trials. EMG-driven modelling based joint torque estimates were obtained from surface and intramuscular EMG. RESULTS: The correlation between the experimental and predicted joint torques was similar when using intramuscular or surface EMG as input to the EMG-driven modelling estimator in both healthy individuals and patients. CONCLUSION: We have provided the first comparison of non-invasive and implanted EMG sensors as input signals for torque estimates in healthy individuals and SCI patients. SIGNIFICANCE: Implanted EMG sensors have the potential to be used as a reliable input for assistive exoskeleton joint torque actuation.

Peripheral electrical stimulation to reduce pathological tremor: a review.

Interventions to reduce tremor in essential tremor (ET) and Parkinson's disease (PD) clinical populations often utilize pharmacological or surgical therapies. However, there can be significant side effects, decline in effectiveness over time, or clinical contraindications for these interventions. Therefore, alternative approaches must be considered and developed. Some non-pharmacological strategies include assistive devices, orthoses and mechanical loading of the tremorgenic limb, while others propose peripheral electrical stimulation. Specifically, peripheral electrical stimulation encompasses strategies that activate motor and sensory pathways to evoke muscle contractions and impact sensorimotor function. Numerous studies report the efficacy of peripheral electrical stimulation to alter tremor generation, thereby opening new perspectives for both short- and long-term tremor reduction. Therefore, it is timely to explore this promising modality in a comprehensive review. In this review, we analyzed 27 studies that reported the use of peripheral electrical stimulation to reduce tremor and discuss various considerations regarding peripheral electrical stimulation: the stimulation strategies and parameters, electrodes, experimental designs, results, and mechanisms hypothesized to reduce tremor. From our review, we identified a high degree of disparity across studies with regard to stimulation patterns, experimental designs and methods of assessing tremor. Having standardized experimental methodology is a critical step in the field and is needed in order to accurately compare results across studies. With this review, we explore peripheral electrical stimulation as an intervention for tremor reduction, identify the limitations and benefits of the current state-of-the-art studies, and provide ideas to guide the development of novel approaches based on the neural circuitries and mechanical properties implied in tremor generation.

Intramuscular Stimulation of Muscle Afferents Attains Prolonged Tremor Reduction in Essential Tremor Patients.

This study proposes and clinically tests intramuscular electrical stimulation below motor threshold to achieve prolonged reduction of wrist flexion/extension tremor in Essential Tremor (ET) patients. The developed system consisted of an intramuscular thin-film electrode structure that included both stimulation and electromyography (EMG) recording electrodes, and a control algorithm for the timing of intramuscular stimulation based on EMG (closed-loop stimulation). Data were recorded from nine ET patients with wrist flexion/extension tremor recruited from the Gregorio Marañón Hospital (Madrid, Spain). Patients participated in two experimental sessions comprising: 1) sensory stimulation of wrist flexors/extensors via thin-film multichannel intramuscular electrodes; and 2) surface stimulation of the nerves innervating the same target muscles. For each session, four of these patients underwent random 60-s trials of two stimulation strategies for each target muscle: 1) selective and adaptive timely stimulation (SATS) - based on EMG of the antagonist muscle; and 2) continuous stimulation (CON) of target muscles. Two patients underwent SATS stimulation trials alone while the other three underwent CON stimulation trials alone in each session. Kinematics of wrist, elbow, and shoulder, together with clinical scales, were used to assess tremor before, right after, and 24 h after each session. Intramuscular SATS achieved, on average, 32% acute (during stimulation) tremor reduction on each trial, while continuous stimulation augmented tremorgenic activity. Furthermore, tremor reduction was significantly higher using intramuscular than surface stimulation. Prolonged reduction of tremor amplitude (24 h after the experiment) was observed in four patients. These results showed acute and prolonged (24 h) tremor reduction using a minimally invasive neurostimulation technology based on SATS of primary sensory afferents of wrist muscles. This strategy might open the possibility of an alternative therapeutic approach for ET patients.

Reorganization of Muscle Coordination Underlying Motor Learning in Cycling Tasks.

The hypothesis of modular control, which stands on the existence of muscle synergies as building blocks of muscle coordination, has been investigated in a great variety of motor tasks and species. Yet, its role during learning processes is still largely unexplored. To what extent is such modular control flexible, in terms of spatial structure and temporal activation, to externally or internally induced adaptations, is a debated issue. To address this question, we designed a biofeedback experiment to induce changes in the timing of muscle activations during leg cycling movements. The protocol consisted in delaying the peak of activation of one target muscle and using its electromyography (EMG) envelope as visual biofeedback. For each of the 10 healthy participants, the protocol was repeated for three different target muscles: Tibialis Anterioris (TA), Gastrocnemius Medialis (GM), and Vastus Lateralis (VL). To explore the effects of the conditioning protocol, we analyzed changes in the activity of eight lower limb muscles by applying different models of modular motor control [i.e., fixed spatial components (FSC) and fixed temporal components (FTC)]. Our results confirm the hypothesis that visual EMG biofeedback is able to induce changes in muscle coordination. Subjects were able to shift the peak of activation of the target muscle, with a delay of (49 ± 27°) across subjects and conditions. This time shift generated a reorganization of all the other muscles in terms of timing and amplitude. By using different models of modular motor control, we demonstrated that neither spatially invariant nor temporally invariant muscle synergies alone were able to account for these changes in muscle coordination after learning, while temporally invariant muscle synergies with adjustments in timing could capture most of muscle activity adaptations observed after the conditioning protocol. These results suggest that short-term learning in rhythmic tasks is built upon synergistic temporal commands that are robust to changes in the task demands.

A thin-film multichannel electrode for muscle recording and stimulation in neuroprosthetics applications.

OBJECTIVE: We propose, design and test a novel thin-film multichannel electrode that can be used for both recording from and stimulating a muscle in acute implants. APPROACH: The system is built on a substrate of polyimide and contains 12 recording and three stimulation sites made of platinum. The structure is 420 µm wide, 20 µm thick and embeds the recording and stimulation contacts on the two sides of the polyimide over an approximate length of 2 cm. We show representative applications in healthy individuals as well as tremor patients. The designed system was tested by a psychometric characterization of the stimulation contacts in six tremor patients and three healthy individuals determining the perception threshold and current limit as well as the success rate in discriminating elicited sensations (electrotactile feedback). Also, we investigated the possibility of using the intramuscular electrode for reducing tremor in one patient by electrical stimulation delivered with timing based on the electromyographic activity recorded with the same electrode. MAIN RESULTS: In the tremor patients, the current corresponding to the perception threshold and the current limit were 0.7 ± 0.2 and 1.4 ± 0.7 mA for the wrist flexor muscles and 0.4 ± 0.2 and 1.5 ± 0.7 mA for the extensors. In one patient, closed-loop stimulation resulted in a decrease of the tremor power >50%. In healthy individuals the perception threshold and current limits were 0.9 ± 0.6 and 2.1 ± 0.6 mA for the extensor carpi radialis muscle. The subjects could distinguish four or six stimulation patterns (two or three stimulation sites × two stimulation current amplitudes) with true positive rate >80% (two subjects) and >60% (one subject), respectively. SIGNIFICANCE: The proposed electrode provides a compact multichannel interface for recording electromyogram and delivering electrical stimulation in applications such as neuroprostheses for tremor suppression and closed-loop myoelectric prostheses.

Adaptation after vastus lateralis denervation in rats demonstrates neural regulation of joint stresses and strains.

In order to produce movements, muscles must act through joints. The translation from muscle force to limb movement is mediated by internal joint structures that permit movement in some directions but constrain it in others. Although muscle forces acting against constrained directions will not affect limb movements, such forces can cause excess stresses and strains in joint structures, leading to pain or injury. In this study, we hypothesized that the central nervous system (CNS) chooses muscle activations to avoid excessive joint stresses and strains. We evaluated this hypothesis by examining adaptation strategies after selective paralysis of a muscle acting at the rat's knee. We show that the CNS compromises between restoration of task performance and regulation of joint stresses and strains. These results have significant implications to our understanding of the neural control of movements, suggesting that common theories emphasizing task performance are insufficient to explain muscle activations during behaviors.