Design and Control of Mechanoneural Interfaces for Neuroprosthetic Limbs

Within the past two decades, numerous attempts have been made to fully reconstruct bionic gait via signals derived from the human nervous system. However, human gait has been difficult to emulate due to the high resolution of both efferent and afferent signaling required to replicate coordinated volitional and reflexive motor commands. Even invasive neural interfaces providing functional feedback from the bionic leg have been unable to demonstrate biomimetic gait. To compound the difficulty, there is limited understanding of the fundamental level of afferent feedback necessary to facilitate a high degree of neuroprosthetic integration for human locomotion. In this thesis, we investigate the impact of preserving afferent feedback in residual limbs on the sensorimotor responses of individuals with below-knee amputations. Additionally, we present a neuroprosthetic framework that fully reconstructs biomimetic gait from neural information generated by individuals with below-knee amputation. We have achieved the level of neuroprosthetic integration necessary to execute versatile gait through a surgically-constructed mechanoneural interface that enhances native muscle afferents within the amputated residuum. Finally, we develop a myoneural actuator technology in a rodent model, enabling the design of a novel mechanoneural interface that allows for the direct modulation of proprioceptive afferents. These advancements have the potential to significantly improve the quality of life for individuals with amputations and further the development of advanced surgical and neuroprosthetic technologies.Ph.D

Pressure based MRI-compatible muscle fascicle length and joint angle estimation

Background: Functional magnetic resonance imaging (fMRI) provides critical information about the neurophysiology of the central nervous systems (CNS), posing clinical significance for the understanding of neuropathologies and advancement of rehabilitation. Typical fMRI study designs include subjects performing designed motor tasks within specific time frames, in which fMRI data are then analyzed by assuming that observed functional brain activations correspond to the designed tasks. Therefore, developing MRI-compatible sensors that enable real-time monitoring of subjects’ task performances would allow for highly accurate fMRI studies. While several MRI-compatible sensors have been developed, none have demonstrated the ability to measure individual muscle fascicle length during fMRI, which could help uncover the complexities of the peripheral and central nervous systems. Furthermore, previous MRI-compatible sensors have been focused on biologically intact populations, limiting accessibility to populations such as those who have undergone amputation. Methods: We propose a lightweight, low-cost, skin impedance-insensitive pressure-based muscular motion sensor (pMMS) that provides reliable estimates of muscle fascicle length and joint angle. The muscular motions are captured through measured pressure changes in an air pocket wrapped around the muscle of interest, corresponding to its muscular motion. The muscle fascicle length and joint angle are then estimated from the measured pressure changes based on the proposed muscle-skin-sensor interaction dynamics. Furthermore, we explore an integration method of multiple pMMS systems to expand the sensor capacity of estimating muscle fascicle length and joint angle. Ultrasound imaging paired with joint encoder measurements are utilized to assess pMMS estimation accuracy of muscle fascicle length in the tibialis anterior (TA) and ankle joint angle, respectively, of five biologically intact subjects. Results: We found that a single pMMS sufficiently provides robust and accurate estimations of TA muscle fascicle length and ankle joint angle during dorsiflexion at various speeds and amplitudes. Further, differential pressure readings from two pMMSs, in which each pMMS were proximally and distally placed, were able to mitigate errors due to perturbations, expanding pMMS capacity for muscle fascicle length and ankle joint angle estimation during the full range of plantar flexion and dorsiflexion. Conclusions: Our results from this study demonstrate the feasibility of the pMMS system to further be incorporated in fMRI settings for real-time monitoring of subjects’ task performances, allowing sophisticated fMRI study designs

Retinal supplementation augments optogenetic stimulation efficacy in vivo

© 2019 IOP Publishing Ltd. Objective. Over the last two decades, optical control of neuronal activity in the central nervous system has seen rapid development, demonstrating the utility of optogenetics as both an experimental and therapeutic tool. Conversely, applications of optogenetics in the peripheral nervous system have been relatively constrained by the challenges of temporally variable opsin expression, light penetration and immune attack of non-native opsins. Whilst opsin expression can be increased significantly through high-concentration viral induction, subsequent attack by the immune system causes temporal decay and high variability in electrophysiological response. Approach. In this study, we present a method to circumvent the aforementioned challenges by locally supplementing all-trans-retinal (ATR) (via a slow release pellet) to increase tissue photosensitivity in transgenic mice expressing channelrhodopsin 2 (ChR2) in nerves. Main results. In mice supplemented with ATR, we demonstrate enhanced electrophysiological activation and fatigue tolerance in response to optical stimulation for six weeks. Significance. Local supplementation of ATR enables improved optogenetic stimulation efficacy in peripheral nerves. This method enables greater exploration of neurophysiology and development of clinically-viable optogenetic treatments in the peripheral nervous system

Closed-loop functional optogenetic stimulation

Optogenetics is a promising alternative approach for restoration of neuromuscular function. Here the authors establish a closed-loop functional optogenetic stimulation for the control of limb joint angle in murine models, which demonstrates improved control and less fatigue than electrical stimulation systems

Resting state neurophysiology of agonist–antagonist myoneural interface in persons with transtibial amputation

Abstract The agonist–antagonist myoneural interface (AMI) is an amputation surgery that preserves sensorimotor signaling mechanisms of the central-peripheral nervous systems. Our first neuroimaging study investigating AMI subjects conducted by Srinivasan et al. (2020) focused on task-based neural signatures, and showed evidence of proprioceptive feedback to the central nervous system. The study of resting state neural activity helps non-invasively characterize the neural patterns that prime task response. In this study on resting state functional magnetic resonance imaging in AMI subjects, we compared functional connectivity in patients with transtibial AMI (n = 12) and traditional (n = 7) amputations (TA). To test our hypothesis that we would find significant neurophysiological differences between AMI and TA subjects, we performed a whole-brain exploratory analysis to identify a seed region; namely, we conducted ANOVA, followed by t-test statistics to locate a seed in the salience network. Then, we implemented a seed-based connectivity analysis to gather cluster-level inferences contrasting our subject groups. We show evidence supporting our hypothesis that the AMI surgery induces functional network reorganization resulting in a neural configuration that significantly differs from the neural configuration after TA surgery. AMI subjects show significantly less coupling with regions functionally dedicated to selecting where to focus attention when it comes to salient stimuli. Our findings provide researchers and clinicians with a critical mechanistic understanding of the effect of AMI amputation on brain networks at rest, which has promising implications for improved neurorehabilitation and prosthetic control

Agonist-antagonist myoneural interface amputation preserves proprioceptive sensorimotor neurophysiology in lower limbs

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works The brain undergoes marked changes in function and functional connectivity after limb amputation. The agonist-antagonist myoneural interface (AMI) amputation is a procedure that restores physiological agonist-antagonist muscle relationships responsible for proprioceptive sensory feedback to enable greater motor control. We compared results from the functional neuroimaging of individuals (n = 29) with AMI amputation, traditional amputation, and no amputation. Individuals with traditional amputation demonstrated a significant decrease in proprioceptive activity, measured by activation of Brodmann area 3a, whereas functional activation in individuals with AMIs was not significantly different from controls with no amputation (P< 0.05). The degree of proprioceptive activity in the brain strongly correlated with fascicle activity in the peripheral muscles and performance on motor tasks (P < 0.05), supporting the mechanistic basis of the AMI procedure. These results suggest that surgical techniques designed to restore proprioceptive peripheral neuromuscular constructs result in desirable central sensorimotor plasticity

Agonist-antagonist muscle strain in the residual limb preserves motor control and perception after amputation

Abstract Background Elucidating underlying mechanisms in subject-specific motor control and perception after amputation could guide development of advanced surgical and neuroprosthetic technologies. In this study, relationships between preserved agonist-antagonist muscle strain within the residual limb and preserved motor control and perception capacity are investigated. Methods Fourteen persons with unilateral transtibial amputations spanning a range of ages, etiologies, and surgical procedures underwent evaluations involving free-space mirrored motions of their lower limbs. Research has shown that varied motor control in biologically intact limbs is executed by the activation of muscle synergies. Here, we assess the naturalness of phantom joint motor control postamputation based on extracted muscle synergies and their activation profiles. Muscle synergy extraction, degree of agonist-antagonist muscle strain, and perception capacity are estimated from electromyography, ultrasonography, and goniometry, respectively. Results Here, we show significant positive correlations (P &lt; 0.005–0.05) between sensorimotor responses and residual limb agonist-antagonist muscle strain. Identified trends indicate that preserving even 20–26% of agonist-antagonist muscle strain within the residuum compared to a biologically intact limb is effective in preserving natural motor control postamputation, though preserving limb perception capacity requires more (61%) agonist-antagonist muscle strain preservation. Conclusions The results suggest that agonist-antagonist muscle strain is a characteristic, readily ascertainable residual limb structural feature that can help explain variability in amputation outcome, and agonist-antagonist muscle strain preserving surgical amputation strategies are one way to enable more effective and biomimetic sensorimotor control postamputation. </jats:sec

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