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.

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

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.

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.

Erratum: Publisher Correction: Agonist-antagonist muscle strain in the residual limb preserves motor control and perception after amputation.

[This corrects the article DOI: 10.1038/s43856-022-00162-z.].

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

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 < 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.

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.

Development of a Classical Conditioning Task for Humans Examining Phasic Heart Rate Responses to Signaled Appetitive Stimuli: A Pilot Study.

Cardiac responses to appetitive stimuli have been studied as indices of motivational states and attentional processes, the former being associated with cardiac acceleration and latter deceleration. Very few studies have examined heart rate changes in appetitive classical conditioning in humans. The current study describes the development and pilot testing of a classical conditioning task to assess cardiac responses to appetitive stimuli and cues that reliably precede them. Data from 18 adults were examined. They were shown initially neutral visual stimuli (putative CS) on a computer screen followed by pictures of high-caloric food (US). Phasic cardiac deceleration to food images was observed, consistent with an orienting response to motivationally significant stimuli. Similar responses were observed to non-appetitive stimuli when they were preceded by the cue associated with the food images, suggesting that attentional processes were engaged by conditioned stimuli. These autonomic changes provide significant information about classical conditioning effects in humans.

Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation.

Despite advancements in prosthetic technologies, patients with amputation today suffer great diminution in mobility and quality of life. We have developed a modified below-knee amputation (BKA) procedure that incorporates agonist-antagonist myoneural interfaces (AMIs), which surgically preserve and couple agonist-antagonist muscle pairs for the subtalar and ankle joints. AMIs are designed to restore physiological neuromuscular dynamics, enable bidirectional neural signaling, and offer greater neuroprosthetic controllability compared to traditional amputation techniques. In this prospective, nonrandomized, unmasked study design, 15 subjects with AMI below-knee amputation (AB) were matched with 7 subjects who underwent a traditional below-knee amputation (TB). AB subjects demonstrated significantly greater control of their residual limb musculature, production of more differentiable efferent control signals, and greater precision of movement compared to TB subjects (P < 0.008). This may be due to the presence of greater proprioceptive inputs facilitated by the significantly higher fascicle strains resulting from coordinated muscle excursion in AB subjects (P < 0.05). AB subjects reported significantly greater phantom range of motion postamputation (AB: 12.47 ± 2.41, TB: 10.14 ± 1.45 degrees) when compared to TB subjects (P < 0.05). Furthermore, AB subjects also reported less pain (12.25 ± 5.37) than TB subjects (17.29 ± 10.22) and a significant reduction when compared to their preoperative baseline (P < 0.05). Compared with traditional amputation, the construction of AMIs during amputation confers the benefits of enhanced physiological neuromuscular dynamics, proprioception, and phantom limb perception. Subjects' activation of the AMIs produces more differentiable electromyography (EMG) for myoelectric prosthesis control and demonstrates more positive clinical outcomes.

A Paradigm Shift in Critical Care Infrastructure in Complex Settings: Evaluating an Ultraportable Operating Room to Improve Field Surgical Safety.

INTRODUCTION: Scarcity of operating rooms and personal protective equipment in far-forward field settings make surgical infections a potential concern for combat mortality and morbidity. Surgical and transport personnel also face infectious risks from bodily fluid exposures. Our study aimed to describe the serial, proof-of-concept testing of the SurgiBox technology: an inflatable sterile environment that addresses the aforementioned problems, fits on gurneys and backpacks, and drapes over incisions. MATERIALS AND METHODS: The SurgiBox environmental control unit and inflatable enclosure were optimized over five generations based on iterative feedback from stakeholders experienced in surgery in austere settings. The airflow system was developed by analytic modeling, verified through in silico modeling in SOLIDWORKS, and confirmed with prototype smoke-trail checking. Particulate counts evaluated the enclosure's ability to control and mitigate users' exposures to potentially infectious contaminants from the surgical field in various settings. SurgiBox enclosures were setup over a mannequin's torso, in a configuration and position for either thoracic or abdominal surgery. A particle counter was serially positioned in sternotomy and laparotomy positions, as well as bilateral flank positions. This setup was repeated with open ports exposing the enclosure to the external environment. To simulate stress scenarios, sampling was repeated with enclosure measurements during an increase in external particulate concentration. RESULTS: The airflow technology effectively kept contaminants away from the incision and maintained a pressure differential to reduce particle entry. Benchtop testing demonstrated that even when ports were opened or the external environment had high contaminant burden, the enclosed surgical field consistently registered 0 particle count in all positions. Time from kit opening to incision averaged 54.5 seconds, with the rate-limiting step being connecting the environmental control unit to the enclosure. The portable kit weighted 5.9 lbs. CONCLUSIONS: Analytic, in silico, and mechanical airflow modeling and benchtop testing have helped to quantify the SurgiBox system's reliability in creating and maintaining an operating room-quality surgical field within the enclosure as well as protecting the surgical team outside the enclosure. More recent and ongoing work has focused on specifying optimal use settings in the casualty chain of care, expanding support for circumferential procedures, automating airflow control, and accelerating system setup. SurgiBox's ultimate goal is to take timely, safe surgery to patients in even the most austere of settings.

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

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.