Continuous neural control of a bionic limb restores biomimetic gait after amputation.

For centuries scientists and technologists have sought artificial leg replacements that fully capture the versatility of their intact biological counterparts. However, biological gait requires coordinated volitional and reflexive motor control by complex afferent and efferent neural interplay, making its neuroprosthetic emulation challenging after limb amputation. Here we hypothesize that continuous neural control of a bionic limb can restore biomimetic gait after below-knee amputation when residual muscle afferents are augmented. To test this hypothesis, we present a neuroprosthetic interface consisting of surgically connected, agonist-antagonist muscles including muscle-sensing electrodes. In a cohort of seven leg amputees, the interface is shown to augment residual muscle afferents by 18% of biologically intact values. Compared with a matched amputee cohort without the afferent augmentation, the maximum neuroprosthetic walking speed is increased by 41%, enabling equivalent peak speeds to persons without leg amputation. Further, this level of afferent augmentation enables biomimetic adaptation to various walking speeds and real-world environments, including slopes, stairs and obstructed pathways. Our results suggest that even a small augmentation of residual muscle afferents restores biomimetic gait under continuous neuromodulation in individuals with leg amputation.

Variable-stiffness prosthesis improves biomechanics of walking across speeds compared to a passive device.

Ankle push-off power plays an important role in healthy walking, contributing to center-of-mass acceleration, swing leg dynamics, and accounting for 45% of total leg power. The majority of existing passive energy storage and return prostheses for people with below-knee (transtibial) amputation are stiffer than the biological ankle, particularly at slower walking speeds. Additionally, passive devices provide insufficient levels of energy return and push-off power, negatively impacting biomechanics of gait. Here, we present a clinical study evaluating the kinematics and kinetics of walking with a microprocessor-controlled, variable-stiffness ankle-foot prosthesis (945 g) compared to a standard low-mass passive prosthesis (Ottobock Taleo, 463 g) with 7 study participants having unilateral transtibial amputation. By modulating prosthesis stiffness under computer control across walking speeds, we demonstrate that there exists a stiffness that increases prosthetic-side energy return, peak power, and center-of-mass push-off work, and decreases contralateral limb peak ground reaction force compared to the standard passive prosthesis across all evaluated walking speeds. We demonstrate a significant increase in center-of-mass push-off work of 26.1%, 26.2%, 29.6% and 29.9% at 0.75 m/s, 1.0 m/s, 1.25 m/s, and 1.5 m/s, respectively, and a significant decrease in contralateral limb ground reaction force of 3.1%, 3.9%, and 3.2% at 1.0 m/s, 1.25 m/s, and 1.5 m/s, respectively. This study demonstrates the potential for a quasi-passive microprocessor-controlled variable-stiffness prosthesis to increase push-off power and energy return during gait at a range of walking speeds compared to a passive device of a fixed stiffness.

Closed-loop optogenetic neuromodulation enables high-fidelity fatigue-resistant muscle control.

Closed-loop neuroprostheses show promise in restoring motion in individuals with neurological conditions. However, conventional activation strategies based on functional electrical stimulation (FES) fail to accurately modulate muscle force and exhibit rapid fatigue because of their unphysiological recruitment mechanism. Here, we present a closed-loop control framework that leverages physiological force modulation under functional optogenetic stimulation (FOS) to enable high-fidelity muscle control for extended periods of time (>60 minutes) in vivo. We first uncovered the force modulation characteristic of FOS, showing more physiological recruitment and significantly higher modulation ranges (>320%) compared with FES. Second, we developed a neuromuscular model that accurately describes the highly nonlinear dynamics of optogenetically stimulated muscle. Third, on the basis of the optogenetic model, we demonstrated real-time control of muscle force with improved performance and fatigue resistance compared with FES. This work lays the foundation for fatigue-resistant neuroprostheses and optogenetically controlled biohybrid robots with high-fidelity force modulation.

Design, Characterization, and Preliminary Assessment of a Two-Degree-of-Freedom Powered Ankle-Foot Prosthesis.

Powered ankle prostheses have been proven to improve the walking economy of people with transtibial amputation. All commercial powered ankle prostheses that are currently available can only perform one-degree-of-freedom motion in a limited range. However, studies have shown that the frontal plane motion during ambulation is associated with balancing. In addition, as more advanced neural interfaces have become available for people with amputation, it is possible to fully recover ankle function by combining neural signals and a robotic ankle. Accordingly, there is a need for a powered ankle prosthesis that can have active control on not only plantarflexion and dorsiflexion but also eversion and inversion. We designed, built, and evaluated a two-degree-of-freedom (2-DoF) powered ankle-foot prosthesis that is untethered and can support level-ground walking. Benchtop tests were conducted to characterize the dynamics of the system. Walking trials were performed with a 77 kg subject that has unilateral transtibial amputation to evaluate system performance under realistic conditions. Benchtop tests demonstrated a step response rise time of less than 50 milliseconds for a torque of 40 N·m on each actuator. The closed-loop torque bandwidth of the actuator is 9.74 Hz. Walking trials demonstrated torque tracking errors (root mean square) of less than 7 N·m. These results suggested that the device can perform adequate torque control and support level-ground walking. This prosthesis can serve as a platform for studying biomechanics related to balance and has the possibility of further recovering the biological function of the ankle-subtalar-foot complex beyond the existing powered ankles.

Untethered muscle tracking using magnetomicrometry.

Muscle tissue drives nearly all movement in the animal kingdom, providing power, mobility, and dexterity. Technologies for measuring muscle tissue motion, such as sonomicrometry, fluoromicrometry, and ultrasound, have significantly advanced our understanding of biomechanics. Yet, the field lacks the ability to monitor muscle tissue motion for animal behavior outside the lab. Towards addressing this issue, we previously introduced magnetomicrometry, a method that uses magnetic beads to wirelessly monitor muscle tissue length changes, and we validated magnetomicrometry via tightly-controlled in situ testing. In this study we validate the accuracy of magnetomicrometry against fluoromicrometry during untethered running in an in vivo turkey model. We demonstrate real-time muscle tissue length tracking of the freely-moving turkeys executing various motor activities, including ramp ascent and descent, vertical ascent and descent, and free roaming movement. Given the demonstrated capacity of magnetomicrometry to track muscle movement in untethered animals, we feel that this technique will enable new scientific explorations and an improved understanding of muscle function.

Clinical viability of magnetic bead implants in muscle.

Human movement is accomplished through muscle contraction, yet there does not exist a portable system capable of monitoring muscle length changes in real time. To address this limitation, we previously introduced magnetomicrometry, a minimally-invasive tracking technique comprising two implanted magnetic beads in muscle and a magnetic field sensor array positioned on the body's surface adjacent the implanted beads. The implant system comprises a pair of spherical magnetic beads, each with a first coating of nickel-copper-nickel and an outer coating of Parylene C. In parallel work, we demonstrate submillimeter accuracy of magnetic bead tracking for muscle contractions in an untethered freely-roaming avian model. Here, we address the clinical viability of magnetomicrometry. Using a specialized device to insert magnetic beads into muscle in avian and lagomorph models, we collect data to assess gait metrics, bead migration, and bead biocompatibility. For these animal models, we find no gait differences post-versus pre-implantation, and bead migration towards one another within muscle does not occur for initial bead separation distances greater than 3 cm. Further, using extensive biocompatibility testing, the implants are shown to be non-irritant, non-cytotoxic, non-allergenic, and non-irritating. Our cumulative results lend support for the viability of these magnetic bead implants for implantation in human muscle. We thus anticipate their imminent use in human-machine interfaces, such as in control of prostheses and exoskeletons and in closed-loop neuroprosthetics to aid recovery from neurological disorders.

Rejecting Impulse Artifacts from Surface EMG Signals using Real-time Cumulative Histogram Filtering.

This paper presents a cumulative histogram filtering (CHF) algorithm to filter impulsive artifacts within surface electromyograhy (sEMG) signal for time-domain signal feature extraction. The proposed CHF algorithm filters sEMG signals by extracting a continuous subset of amplitude-sorted values within a real-time window of measured samples using information about the probabilistic distribution of sEMG amplitude. For real-time deployment of the proposed CHF algorithm on an embedded computing platform, we also present an efficient, iterative implementation of the proposed algorithm. The proposed CHF algorithm was evaluated on synthetic impulse artifacts superimposed upon undisturbed sEMG recorded from a subject with transtibial amputation. Results suggest that the CHF algorithm effectively suppresses the simulated impulse artifacts while preserving a minimum signal-to-noise ratio of 95% and an average Pearson correlation of 0.99 compared to the undisturbed sEMG recordings.

Spatiotemporally Synchronized Surface EMG and Ultrasonography Measurement Using a Flexible and Low-Profile EMG Electrode.

The temporally synchronized recording of muscle activity and fascicle dynamics is essential in understanding the neurophysiology of human motor control which could promote developments of effective rehabilitation strategies and assistive technologies. Surface electromyography (sEMG) and ultrasonography provide easy-to-use, low-cost, and noninvasive modalities to assess muscle activity and fascicle dynamics, and have been widely used in both clinical and lab settings. However, due to size of these sensors and limited skin surface area, it is extremely challenging to collect data from a muscle of interest in a spatially as well as temporally synchronized manner. Here, we introduce a low-cost, noninvasive flexible electrode that provides high quality sEMG recording, while also enabling spatiotemporally synchronized ultrasonography recordings. The proposed method was verified by comparing ultrasonography of a phantom and a tibialis anterior (TA) muscle during dorsiflexion and plantarflexion with and without the electrode acutely placed under an ultrasound probe. Our results show no significant artifact in ultrasonography from both the phantom and TA fascicle strains due to the presence of the electrode, demonstrating the capability of spatiotemporally synchronized sEMG and ultrasonography recording.

Acquisition of Surface EMG Using Flexible and Low-Profile Electrodes for Lower Extremity Neuroprosthetic Control.

For persons with lower extremity (LE) amputation, acquisition of surface electromyography (sEMG) from within the prosthetic socket remains a significant challenge due to the dynamic loads experienced during the gait cycle. However, these signals are critical for both understanding the clinical effects of LE amputation and determining the desired control trajectories of active LE prostheses. Current solutions for collecting within-socket sEMG are generally (i) incompatible with a subject's prescribed prosthetic socket and liners, (ii) uncomfortable, and (iii) expensive. This study presents an alternative within-socket sEMG acquisition paradigm using a novel flexible and low-profile electrode. First, the practical performance of this Sub-Liner Interface for Prosthetics (SLIP) electrode is compared to that of commercial Ag/AgCl electrodes within a cohort of subjects without amputation. Then, the corresponding SLIP electrode sEMG acquisition paradigm is implemented in a single subject with unilateral transtibial amputation performing unconstrained movements and walking on level ground. Finally, a quantitative questionnaire characterizes subjective comfort for SLIP electrode and commercial Ag/AgCl electrode instrumentation setups. Quantitative analyses suggest comparable signal qualities between SLIP and Ag/AgCl electrodes while qualitative analyses suggest the feasibility of using the SLIP electrode for real-time sEMG data collection from load-bearing, ambulatory subjects with LE amputation.

An Ankle-Foot Prosthesis for Rock Climbing Augmentation.

This research presents the design and preliminary evaluation of an electromyographically (EMG) controlled 2-degree-of-freedom (DOF) ankle-foot prosthesis designed to enhance rock climbing ability in persons with transtibial amputation. The prosthesis comprises motorized ankle and subtalar joints, and is capable of emulating some key biomechanical behaviors exhibited by the ankle-foot complex during rock climbing maneuvers. The free space motion of the device is volitionally controlled via input from EMG surface electrodes embedded in a custom silicone liner worn on the residual limb. The device range of motion is 0.29 radians of each dorsiflexion and plantar flexion, and 0.39 radians each of inversion and eversion. Preliminary evaluation of the device was conducted, validating the system mass of 1292 grams, build height of 250 mm, joint velocity of 2.18 radians/second, settling time of 120 milliseconds, and steady state error of 0.008 radians. Clinical evaluation of the device was performed during a preliminary study with one subject with transtibial amputation. Joint angles of the ankle-foot, knee, and hip were measured during rock climbing with the robotic prosthesis and with a traditional passive prosthesis. We found that the robotic prosthesis increases the range of achieved ankle and subtalar positions compared to a standard passive prosthesis. In addition, maximum knee flexion and hip flexion angles are decreased while climbing with the robotic prosthesis. These results suggest that a lightweight, actuated, 2-DOF EMG-controlled robotic ankle-foot prosthesis can improve ankle and subtalar range of motion and climbing biomechanical function.

Flexible Dry Electrodes for EMG Acquisition within Lower Extremity Prosthetic Sockets.

Acquisition of surface electromyography (sEMG) from a person with an amputated lower extremity (LE) during prosthesis-assisted walking remains a significant challenge due to the dynamic nature of the gait cycle. Current solutions to sEMG-based neural control of active LE prostheses involve a combination of customized electrodes, prosthetic sockets, and liners. These technologies are generally: (i) incompatible with a subject's existing prosthetic socket and liners; (ii) uncomfortable to use; and (iii) expensive. This paper presents a flexible dry electrode design for sEMG acquisition within LE prosthetic sockets which seeks to address these issues. Design criteria and corresponding design decisions are explained and a proposed flexible electrode prototype is presented. Performances of the proposed electrode and commercial Ag/AgCl electrodes are compared in seated subjects without amputations. Quantitative analyses suggest comparable signal qualities for the proposed novel electrode and commercial electrodes. The proposed electrode is demonstrated in a subject with a unilateral transtibial amputation wearing her own liner, socket, and the portable sEMG processing platform in a preliminary standing and level ground walking study. Qualitative analyses suggest the feasibility of real-time sEMG data collection from load-bearing, ambulatory subjects.

Acute and 90-day subchronic toxicity studies of Silk peptide E5K6, in Sprague-Dawley rats.

Acute and 90-day subchronic oral toxicity studies of Silk peptide E5K6 were performed in Sprague-Dawley rats. In the acute toxicity study, Silk peptide E5K6 was administered orally to male and female rats at a single dose of 2000 and 5000 mg/kg. Mortality, clinical signs and body weight changes were monitored for 14 days. There were no treatment-related changes in these parameters. Therefore, the Approximate Lethal Dose (ALD) of Silk peptide E5K6 in male and female rats is higher than 5000 mg/kg. In the subchronic toxicity study, Silk peptide E5K6 was administered orally to male and female rats for 90 days at a single dose of 500, 1000, and 2000 mg/kg. There were no toxicologically significant changes in clinical signs, body weight, food and water consumptions, ophthalmoscopic examination, urinalysis, hematological and serum biochemical examinations, necropsy findings, organ weights and histopathological examination of all of the animals treated with Silk peptide E5K6. These results suggest that the oral No Observed Adverse-Effect Level (NOAEL) of Silk peptide E5K6 is greater than 2000 mg/kg/day in both sexes and the target organs were not established.