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Objectives: Neuroprosthetic devices can improve quality of life by providing an alternative option for motor function lost after spinal cord injury, stroke, and other central nervous system disorders. The objective of this study is to analyze the outcomes of implanted pulse generators that our research group installed in volunteers with paralysis to assist with lower extremity function over a 25-year period, specifically, to determine survival rates and common modes of malfunction, reasons for removal or revision, and precipitating factors or external events that may have adversely influenced device performance., Materials and Methods: Our implantable receiver-stimulator (IRS-8) and implantable stimulator-telemeter (IST-12 and IST-16) device histories were retrospectively reviewed through surgical notes, regulatory documentation, and manufacturing records from 1996 to 2021., Results: Most of the 65 devices (64.6%) implanted in 43 volunteers remain implanted and operational. Seven underwent explantation owing to infection; seven had internal failures, and six were physically broken by external events. Of the 22 devices explanted, 15 were successfully replaced to restore recipients' enhanced functionality. There were no instances of sepsis or major health complications. The five infections that followed all 93 IRS and IST lower extremity research surgeries during this period indicate a pooled infection rate of 5.4%. The Kaplan-Meier analysis of technical malfunctions between the implant date and most recent follow-up shows five-, ten-, and 20-year device survival rates of 92%, 84%, and 71%, respectively., Conclusions: Incidence of malfunction is similar to, whereas infection rates are slightly higher than, other commonly implanted medical devices. Future investigations will focus on infection prevention, modifying techniques on the basis of recipient demographics, lifestyle factors, and education, and integrating similar experience of motor neuroprostheses used in other applications., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. All rights reserved.)

Over 50% of individuals with lower limb loss report a fear of falling and avoiding daily activities partly due to a lack of plantar sensation. Providing direct somatosensory feedback via neural stimulation holds promise for addressing this issue. In this study, three individuals with lower limb loss received a sensory neuroprosthesis (SNP) that provided plantar somatosensory feedback corresponding to prosthesis-floor interactions perceived as arising from the missing foot generated by electrically activating the peripheral nerves in the residuum. Participants walked on a treadmill while receiving perturbations involving brief increases in the belt speed. Perturbations were initiated during early stance and randomly delivered to intact and prosthetic sides with the SNP active or inactive. With the SNP active, participants exhibited decreased trunk angular sway and peak trunk flexion angular velocity during recovery from both prosthetic and intact side perturbations. For prosthetic side perturbations, peak ground reaction force magnitudes decreased when the SNP was active. For intact side perturbations, peak ground reaction force magnitudes increased on the prosthetic side's first recovery step after the perturbation, which resulted in a more symmetric recovery because the force approached the response on the intact side's first recovery step following a prosthetic side perturbation. These results suggest participants integrated the feedback from the SNP into their sensorimotor control for maintaining stability and gained confidence in relying on their prosthetic limb during recovery. Restoring plantar sensation with a SNP for individuals with lower limb loss could lead to reduced risk of falling by improving recovery from trips., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Iterative Learning Control (ILC) is a promising method for adapting neuromuscular electrical stimulation to facilitate independent walking after upper motor neuron paralysis. However, assumptions made by conventional ILC methods, such as identical initial conditions for each iteration, are unsustainable in the case of human gait. In this study, we implement a musculoskeletal model of a single leg to analyze the consequences of variable initial conditions for data-driven ILC-based stimulation (DDILC) during swing phase of gait. We show that DDILC converges in all tested cases of initial hip angle variability, but that noise arises because of such variability. For the maximum variability case, the output with the largest noise (i.e., the terminal ankle angle) had a standard deviation of 2.1 degrees. Thus, the noise due to initial hip angle variability is shown to be comparable in magnitude to the inherent variability in gait. We also show that exploding gradients and instability eventually occur because of varying initial conditions, but these can be mitigated with established techniques.

For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated position. Functional neuromuscular stimulation (FNS) can restore seated posture and other motor functions after paralysis by applying small electrical currents to the peripheral motor nerves. In particular, the Networked Neuroprosthesis (NNP) is a fully implanted, modular FNS system that is also capable of capturing information from embedded accelerometers for measuring trunk tilt for feedback control of stimulation. The NNP modules containing the accelerometers are located in the body based on surgical constraints. As such, their exact orientations are generally unknown and cannot be easily assessed. In this study, a method for estimating trunk tilt that employed the Gram-Schmidt method to reorient acceleration signals to the anatomical axes of the body was developed and deployed in individuals with SCI using the implanted NNP system. An anatomically realistic model of a human trunk and five accelerometer sensors was developed to verify the accuracy of the reorientation algorithm. Correlation coefficients and root mean square errors (RMSEs) were calculated to compare target trunk tilt estimates and tilt estimates derived from simulated accelerometer signals under a variety of conditions. Simulated trunk tilt estimates with correlation coefficients above 0.92 and RMSEs below 5° were achieved. The algorithm was then applied to accelerometer signals from implanted sensors installed in three NNP recipients. Error analysis was performed by comparing the correlation coefficients and RMSEs derived from trunk tilt estimates calculated from implanted sensor signals to those calculated via motion capture data, which served as the gold standard. NNP-derived trunk tilt estimates exhibited correlation coefficients between 0.80 and 0.95 and RMSEs below 13° for both pitch and roll in most cases. These findings suggest that the algorithm is effective at estimating trunk tilt with the implanted sensors of the NNP system, which implies that the method may be appropriate for extracting feedback signals for control systems for seated stability with NNP technology for individuals who have reduced control of their trunk due to paralysis.

Injury or disease often compromise walking dynamics and negatively impact quality of life and independence. Assessing methods to restore or improve pathological gait can be expedited by examining a global parameter that reflects overall musculoskeletal control. Center of mass (CoM) kinematics follow well-defined trajectories during unimpaired gait, and change predictably with various gait pathologies. We propose a method to estimate CoM trajectories from inertial measurement units (IMUs) using a bidirectional Long Short-Term Memory neural network to evaluate rehabilitation interventions and outcomes. Five non-disabled volunteers participated in a single session of various dynamic walking trials with IMUs mounted on various body segments. A neural network trained with data from four of the five volunteers through a leave-one-subject out cross validation estimated the CoM with average root mean square errors (RMSEs) of 1.44cm, 1.15cm, and 0.40cm in the mediolateral (ML), anteroposterior (AP), and inferior/superior (IS) directions respectively. The impact of number and location of IMUs on network prediction accuracy was determined via principal component analysis. Comparing across all configurations, three to five IMUs located on the legs and medial trunk were the most promising reduced sensor sets for achieving CoM estimates suitable for outcome assessment. Lastly, the networks were tested on data from an individual with hemiparesis with the greatest error increase in the ML direction, which could stem from asymmetric gait. These results provide a framework for assessing gait deviations after disease or injury and evaluating rehabilitation interventions intended to normalize gait pathologies.

Spinal cord injury (SCI) can cause paralysis of trunk and hip musculature that negatively impacts seated balance and ability to lean away from an upright posture and interact fully with the environment. Constant levels of electrical stimulation of peripheral nerves can activate typically paralyzed muscles and aid in maintaining a single upright seated posture. However, in the absence of a feedback controller, such seated postures and leaning motions are inherently unstable and unable to respond to perturbations. Three individuals with motor complete SCI who had previously received a neuroprosthesis capable of activating the hip and trunk musculature volunteered for this study. Subject-specific muscle synergies were identified through system identification of the lumbar moments produced via neural stimulation. Synergy-based calculations determined the real-time stimulation parameters required to assume leaning postures. When combined with a proportional, integral, derivative (PID) feedback controller and an accelerometer to infer trunk orientation, all individuals were able to assume non-erect postures of 30-40° flexion and 15° lateral bending. Leaning postures increased forward reaching capabilities by 10.2, 46.7, and 16 cm respectively for each subject when compared with no stimulation. Additionally, the leaning controllers were able to resist perturbations of up to 90 N, and all subjects perceived the leaning postures as moderately to very stable. Implementation of leaning controllers for neuroprostheses have the potential of expanding workspaces, increasing independence, and facilitating activities of daily living for individuals with paralysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Friederich, Lombardo, Foglyano, Audu and Triolo.)

Introduction: Individuals with lower limb loss experience an increased risk of falls partly due to the lack of sensory feedback from their missing foot. It is possible to restore plantar sensation perceived as originating from the missing foot by directly interfacing with the peripheral nerves remaining in the residual limb, which in turn has shown promise in improving gait and balance. However, it is yet unclear how these electrically elicited plantar sensation are integrated into the body's natural sensorimotor control reflexes. Historically, the H-reflex has been used as a model for investigating sensorimotor control. Within the spinal cord, an array of inputs, including plantar cutaneous sensation, are integrated to produce inhibitory and excitatory effects on the H-reflex., Methods: In this study, we characterized the interplay between electrically elicited plantar sensations and this intrinsic reflex mechanism. Participants adopted postures mimicking specific phases of the gait cycle. During each posture, we electrically elicited plantar sensation, and subsequently the H-reflex was evoked both in the presence and absence of these sensations., Results: Our findings indicated that electrically elicited plantar sensations did not significantly alter the H-reflex excitability across any of the adopted postures., Conclusion: This suggests that individuals with lower limb loss can directly benefit from electrically elicited plantar sensation during walking without disrupting the existing sensory signaling pathways that modulate reflex responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential competing interest., (Copyright © 2023 Li, Triolo and Charkhkar.)

Introduction: Lower limb prosthesis users often struggle to navigate uneven terrain or ambulate in low light conditions where it can be challenging to rely on visual cues for balance and walking. Sensory feedback about foot-floor interactions may allow users to reduce reliance on secondary sensory cues and improve confidence and speed when navigating difficult terrain. Our group has developed a Sensory Neuroprosthesis (SNP) to restore sensation to people with lower limb amputation by pairing electrical stimulation of nerves in the residual limb applied via implanted neurotechnology with pressure sensors in the insole of a standard prosthesis. Stimulation applied to the nerves evoked sensations perceived as originating on the missing leg and foot., Methods: This qualitative case study reports on the experiences of a 68-year-old with a unilateral trans-tibial amputation who autonomously used the SNP at home for 31 weeks. Interview data collected throughout the study period was analyzed using a grounded theory approach with constant comparative methods to understand his experience with this novel technology and its impacts on his daily life., Results: A conceptual model was developed that explained the experience of integrating SNP-provided sensory feedback into his body and motor plans. The model described the requirements of integration, which were a combination of a low level of mental focus and low stimulation levels. While higher levels of stimulation and focus could result in distinct sensory percepts and various phantom limb experiences, optimal integration was associated with SNP-evoked sensation that was not readily perceivable. Successful sensorimotor integration of the SNP resulted in improvements to locomotion, a return to a more normal state, an enhancement of perceived prosthesis utility, and a positive outlook on the experience., Discussion: These outcomes emerged over the course of the nearly 8 month study, suggesting that findings from long-term home studies of SNPs may differ from those of short-term in-laboratory tests. Our findings on the experience of sensorimotor integration of the SNP have implications for the optimal training of SNP users and the future deployment of clinical SNP systems for long-term home use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schmitt, Wright, Triolo, Charkhkar and Graczyk.)

Background: Restoring or improving seated stability after spinal cord injury (SCI) can improve the ability to perform activities of daily living by providing a dynamic, yet stable, base for upper extremity motion. Seated stability can be obtained with activation of the otherwise paralyzed trunk and hip musculature with neural stimulation, which has been shown to extend upper limb reach and improve seated posture., Methods: We implemented a proportional, integral, derivative (PID) controller to maintain upright seated posture by simultaneously modulating both forward flexion and lateral bending with functional neuromuscular stimulation. The controller was tested with a functional reaching task meant to require trunk movements and impart internal perturbations through rapid changes in inertia due to acquiring, moving, and replacing objects with one upper extremity. Five subjects with SCI at various injury levels who had received implanted stimulators targeting their trunk and hip muscles participated in the study. Each subject was asked to move a weighted jar radially from a center home station to one of three target stations. The task was performed with the controller active, inactive, or with a constant low level of neural stimulation. Trunk pitch (flexion) and roll (lateral bending) angles were measured with motion capture and plotted against each other to generate elliptical movement profiles for each task and condition. Postural sway was quantified by calculating the ellipse area. Additionally, the mean effective reach (distance between the shoulder and wrist) and the time required to return to an upright posture was determined during reaching movements., Results: Postural sway was reduced by the controller in two of the subjects, and mean effective reach was increased in three subjects and decreased for one. Analysis of the major direction of motion showed return to upright movements were quickened by 0.17 to 0.32 s. A 15 to 25% improvement over low/no stimulation was observed for four subjects., Conclusion: These results suggest that feedback control of neural stimulation is a viable way to maintain upright seated posture by facilitating trunk movements necessary to complete reaching tasks in individuals with SCI. Replication of these findings on a larger number of subjects would be necessary for generalization to the various segments of the SCI population., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A two-part simulation process was developed to investigate the facilitation of vertical patient lifts with functional neuromuscular stimulation (FNS) in individuals with spinal cord injury (SCI). First, external lifting forces representing caregiver assistance were applied to a 3D musculoskeletal model representing the patient and optimized to enforce a specific lifting trajectory during a forward dynamic simulation. The process was repeated with and without the activation of the knee, hip, and trunk extensor muscles of the patient model to represent contractions of the paralyzed muscles generated via FNS. Secondly, the spinal compression experienced by a caregiver at the L5/S1 joint while generating these external lifting forces was estimated using a second musculoskeletal model representing the caregiver. Simulation without muscle activation predicted spinal compression in the caregiver model approximately 1.3 × the National Institute for Occupational Safety and Health (NIOSH) recommended "Action Limit." Comparatively, simulations with two unique patterns of muscle activation both predicted caregiver spinal compressions below NIOSH recommendations. These simulation results support the hypothesis that FNS activation of a patient's otherwise paralyzed muscles would lower the force output required of a caregiver during a dependent transfer, thus lowering the spinal compression and risk of injury experienced by a caregiver., (© 2022. International Federation for Medical and Biological Engineering.)

Feedback control of functional neuromuscular stimulation has the potential to improve daily function for individuals with spinal cord injuries (SCIs) by enhancing seated stability. Our fully implanted networked neuroprosthesis (NNP) can provide real-time feedback signals for controlling the trunk through accelerometers embedded in modules distributed throughout the trunk. Typically, inertial sensors are aligned with the relevant body segment. However, NNP implanted modules are placed according to surgical constraints and their precise locations and orientations are generally unknown. We have developed a method for calibrating multiple randomly oriented accelerometers and fusing their signals into a measure of trunk orientation. Six accelerometers were externally attached in random orientations to the trunks of six individuals with SCI. Calibration with an optical motion capture system resulted in RMSE below 5° and correlation coefficients above 0.97. Calibration with a handheld goniometer resulted in RMSE of 7° and correlation coefficients above 0.93. Our method can obtain trunk orientation from a network of sensors without a priori knowledge of their relationships to the body anatomical axes. The results of this study will be invaluable in the design of feedback control systems for stabilizing the trunk of individuals with SCI in combination with the NNP implanted technology.

The trunk movements of an individual paralyzed by spinal cord injury (SCI) can be restored by functional neuromuscular stimulation (FNS), which applies low-level current to the motor nerves to activate the paralyzed muscles to generate useful torques, to actuate the trunk. FNS can be modulated to vary the biotorques to drive the trunk to follow a user-defined reference motion and maintain it at a desired postural set-point. However, a stabilizing modulation policy (i.e., control law) is difficult to derive as the biomechanics of the spine and pelvis are complex and the neuromuscular dynamics are highly nonlinear, nonautonomous, and input redundant. Therefore, a control method that can stabilize it with FNS without knowing the accurate skeletal and neuromuscular dynamics is desired. To achieve this goal, we propose a control framework consisting of a robust control module that generates stabilizing torques while an artificial neural network-based mapping mechanism with an anatomy-based updating law ensures that the muscle-generated torques converge to the stabilizing values. For the robust control module, two sliding-mode robust controllers (i.e., a high compensation controller and an adaptive controller), were investigated. System stability of the proposed control method was rigorously analyzed based on the assumption that the skeletal dynamics can be approximated by Euler-Lagrange equations with bounded disturbances, which enables the generalization of the control framework. We present experiments in a simulation environment where an anatomically realistic three-dimensional musculoskeletal model of the human trunk moved in the anterior- posterior and medial-lateral directions while perturbations were applied. The satisfactory simulation results suggest the potential of this control technique for trunk tracking tasks in a typical clinical environment., (Copyright © 2022 by ASME.)

Objective: Wheelchair safety is of great importance since falls from wheelchairs are prevalent and often have devastating consequences. We developed an automatic system to detect destabilizing events during wheelchair propulsion under real-world conditions and trigger neural stimulation to stiffen the trunk to maintain seated postures of users with paralysis. Design: Cross-over intervention Setting: Laboratory and community settings Participants: Three able-bodied subjects and three individuals with SCI with previously implanted neurostimulation systems Interventions: An algorithm to detect wheelchair sudden stops was developed. This was used to randomly trigger trunk extensor stimulation during sudden stops events Outcome Measures: Algorithm success and false positive rates were determined. SCI users rated each condition on a seven-point Usability Rating Scale to indicate safety. Results: The system detected sudden stops with a success rate of over 93% in community settings. When used to trigger trunk neurostimulation to ensure stability, the implant recipients consistently reported feeling safer ( P <.05 for 2/3 subjects) with the system while encountering sudden stops as indicated by a 1-3 point change in safety rating. Conclusion: These preliminary results suggest that this system could monitor wheelchair activity and only apply stabilizing neurostimulation when appropriate to maintain posture. Larger scale, unsupervised and longer-term trials at home and in the community are indicated. This system could be generalized and applied to individuals without an implanted stimulation by utilizing surface stimulation, or by actuating a mechanical restraint when necessary, thus allowing unrestricted trunk movements and only restraining the user when necessary to ensure safety. Trial Registration: NCT01474148.

(1) Background: An iterative learning control (ILC) strategy was developed for a "Muscle First" Motor-Assisted Hybrid Neuroprosthesis (MAHNP). The MAHNP combines a backdrivable exoskeletal brace with neural stimulation technology to enable persons with paraplegia due to spinal cord injury (SCI) to execute ambulatory motions and walk upright. (2) Methods: The ILC strategy was developed to swing the legs in a biologically inspired ballistic fashion. It maximizes muscular recruitment and activates the motorized exoskeletal bracing to assist the motion as needed. The control algorithm was tested using an anatomically realistic three-dimensional musculoskeletal model of the lower leg and pelvis suitably modified to account for exoskeletal inertia. The model was developed and tested with the OpenSim biomechanical modeling suite. (3) Results: Preliminary data demonstrate the efficacy of the controller in swing-leg simulations and its ability to learn to balance muscular and motor contributions to improve performance and accomplish consistent stepping. In particular, the controller took 15 iterations to achieve the desired outcome with 0.3% error.

Personalization of gait neuroprosthetics is paramount to ensure their efficacy for users, who experience severe limitations in mobility without an assistive device. Our goal is to develop assistive devices that collaborate with and are tailored to their users, while allowing them to use as much of their existing capabilities as possible. Currently, personalization of devices is challenging, and technological advances are required to achieve this goal. Therefore, this paper presents an overview of challenges and research directions regarding an interface with the peripheral nervous system, an interface with the central nervous system, and the requirements of interface computing architectures. The interface should be modular and adaptable, such that it can provide assistance where it is needed. Novel data processing technology should be developed to allow for real-time processing while accounting for signal variations in the human. Personalized biomechanical models and simulation techniques should be developed to predict assisted walking motions and interactions between the user and the device. Furthermore, the advantages of interfacing with both the brain and the spinal cord or the periphery should be further explored. Technological advances of interface computing architecture should focus on learning on the chip to achieve further personalization. Furthermore, energy consumption should be low to allow for longer use of the neuroprosthesis. In-memory processing combined with resistive random access memory is a promising technology for both. This paper discusses the aforementioned aspects to highlight new directions for future research in gait neuroprosthetics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Koelewijn, Audu, del-Ama, Colucci, Font-Llagunes, Gogeascoechea, Hnat, Makowski, Moreno, Nandor, Quinn, Reichenbach, Reyes, Sartori, Soekadar, Triolo, Vermehren, Wenger, Yavuz, Fey and Beckerle.)

Seated stability is a major concern of individuals with trunk paralysis. Trunk paralysis is commonly caused by spinal cord injuries (SCI) at or above the thoracic spine. Current methods to improve stability restrict the movement of the user by constraining their trunk to an upright position. Feedback control of functional neuromuscular stimulation (FNS) can help maintain seated stability while still allowing the user to perform movements to accomplish functional tasks. In this study, an individual with a SCI (C7, AIS B) and an implanted stimulator capable of recruiting trunk and hip musculature unilaterally moved a weighted jar on a countertop to and from three prescribed stations directly in front, laterally, and across midline. For comparison, the tasks were performed with constant baseline stimulation and with feedback modulated stimulation based on the tilt of the trunk obtained from an external accelerometer fed into two PID controllers; one for forward trunk pitch and the other for lateral roll. The trunk pitch and roll angles were obtained through motion capture cameras and various measures of postural sway (95% fitted ellipse area, root mean squared (RMS), path length) and the repeatability (coefficient of variation (CoV), variance ratio (VR)) were calculated. Feedback control significantly increased RMS of trunk movement along the major axis of the fitted ellipse, but decreased RMS values during bending along the minor axis of motion. As a result, the fitted ellipse area decreased when deploying the jar to one of the stations and increased with the other two. The CoV indicated reduced variation in the presence of feedback controlled stimulation for all stations, and VR showed higher repeatability in trunk pitch. Plots of the trunk pitch and roll revealed a faster return to upright motion due to feedback stimulation.Clinical relevance- Feedback control in combination with FNS is a viable method to improve seated stability while still allowing dynamic movements in individuals with a SCI, thus addressing a major concern of the population.

Objective: The aims of the study were to reliably determine the two main phases of manual wheelchair propulsion via a simple wearable sensor and to evaluate the effects of modulated trunk and hip stimulation on manual wheelchair propulsion during the challenging tasks of ramp assent and level sprint., Design: An offline tool was created to identify common features between wrist acceleration signals for all subjects who corresponded to the transitions between the contact and recovery phases of manual wheelchair propulsion. For one individual, the acceleration rules and thresholds were implemented for real-time phase-change event detection and modulation of stimulation., Results: When pushing with phase-dependent modulated stimulation, there was a significant (P < 0.05) increase in the primary speed variable (5%-6%) and the subject rated pushing as "moderately or very easy." In the offline analysis, the average phase-change event detection success rate was 79% at the end of contact and 71% at the end of recovery across the group., Conclusions: Signals from simple, wrist-mounted accelerometers can detect the phase transitions during manual wheelchair propulsion instead of elaborate and expensive, instrumented systems. Appropriately timing changes in muscle activation with the propulsion cycle can result in a significant increase in speed, and the system was consistently perceived to be significantly easier to use., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Estimating center of mass (COM) through sensor measurements is done to maintain walking and standing stability with exoskeletons. The authors present a method for estimating COM kinematics through an artificial neural network, which was trained by minimizing the mean squared error between COM displacements measured by a gold-standard motion capture system and recorded acceleration signals from body-mounted accelerometers. A total of 5 able-bodied participants were destabilized during standing through: (1) unexpected perturbations caused by 4 linear actuators pulling on the waist and (2) volitionally moving weighted jars on a shelf. Each movement type was averaged across all participants. The algorithm's performance was quantified by the root mean square error and coefficient of determination (R2) calculated from both the entire trial and during each perturbation type. Throughout the trials and movement types, the average coefficient of determination was 0.83, with 89% of the movements with R2 > .70, while the average root mean square error ranged between 7.3% and 22.0%, corresponding to 0.5- and 0.94-cm error in both the coronal and sagittal planes. COM can be estimated in real time for balance control of exoskeletons for individuals with a spinal cord injury, and the procedure can be generalized for other gait studies.

Our group is developing a cyber-physical walking system (CPWS) for people paralyzed by spinal cord injuries (SCI). The current CPWS consists of a functional neuromuscular stimulation (FNS) system and a powered lower-limb exoskeleton for walking with leg movements in the sagittal plane. We are developing neural control systems that learn to assist the user of this CPWS to walk with stability. In a previous publication (Liu et al., Biomimetics, 2019, 4, 28), we showed a neural controller that stabilized a simulated biped in the sagittal plane. We are considering adding degrees of freedom to the CPWS to allow more natural walking movements and improved stability. Thus, in this paper, we present a new neural network enhanced control system that stabilizes a three-dimensional simulated biped model of a human wearing an exoskeleton. Results show that it stabilizes human/exoskeleton models and is robust to impact disturbances. The simulated biped walks at a steady pace in a range of typical human ambulatory speeds from 0.7 to 1.3 m/s, follows waypoints at a precision of 0.3 m, remains stable, and continues walking forward despite impact disturbances and adapts its speed to compensate for persistent external disturbances. Furthermore, the neural network controller stabilizes human models of different statures from 1.4 to 2.2 m tall without any changes to the control parameters. Please see videos at the following link: 3D biped walking control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Audu, Triolo and Quinn.)

Paralysis of the trunk results in seated instability leading to difficulties performing activities of daily living. Functional neuromuscular stimulation (FNS) combined with control systems have the potential to restore some dynamic functions of the trunk. However, design of multi-joint, multi-muscle control systems requires characterization of the stimulation-driven muscles responsible for movement., Objective: This study characterizes the input-output properties of paralyzed trunk muscles activated by FNS, and explores co-activation of muscles., Methods: Four participants with various spinal cord injuries (C7 AIS-B, T4 AIS-B, T5 AIS-A, C5 AIS-C) were constrained so lumbar forces were transmitted to a load cell while an implanted neuroprosthesis activated otherwise paralyzed hip and paraspinal muscles. Isometric force recruitment curves in the nominal seated position were generated by inputting the level of stimulation (pulse width modulation) while measuring the resulting muscle force. Two participants returned for a second experiment where muscles were co-activated to determine if their actions combined linearly., Results: Recruitment curves of most trunk and hip muscles fit sigmoid shaped curves with a regression coefficient above 0.75, and co-activation of the muscles combined linearly across the hip and lumbar joint. Subject specific perturbation plots showed one subject is capable of resisting up to a 300N perturbation anteriorly and 125N laterally; with some subjects falling considerably below these values., Conclusion: Development of a trunk stability control system can use sigmoid recruitment dynamics and assume muscle forces combine linearly., Significance: This study informs future designs of multi-muscle, and multi-dimensional FNS systems to maintain seated posture and stability.

Interfering with or temporarily eliminating foot-sole tactile sensations causes postural adjustments. Furthermore, individuals with impaired or missing foot-sole sensation, such as lower-limb amputees, exhibit greater postural instability than those with intact sensation. Our group has developed a method of providing tactile feedback sensations projected to the missing foot of lower-limb amputees via electrical peripheral nerve stimulation (PNS) using implanted nerve cuff electrodes. As a step toward effective implementation of the system in rehabilitation and everyday use, we compared postural adjustments made in response to tactile sensations on the missing foot elicited by our system, vibration on the intact foot-sole, and a control condition in which no additional sensory input was applied. Three transtibial amputees with at least a year of experience with tactile sensations provided by our PNS system participated in the study. Participants stood quietly with their eyes closed on their everyday prosthesis while electrically elicited, vibratory, or no additional sensory input was administered for 20 s. Early and steady-state postural adjustments were quantified by center of pressure location, path length, and average angle over the course of each trial. Electrically elicited tactile sensations and vibration both caused shifts in center of pressure location compared to the control condition. Initial (first 3 s) shifts in center of pressure location with electrically elicited or vibratory sensory inputs often differed from shifts measured over the full 20 s trial. Over the full trial, participants generally shifted toward the foot receiving additional sensory input, regardless of stimulation type. Similarities between responses to electrically elicited tactile sensations projected to the missing foot and responses to vibration in analogous regions on the intact foot suggest that the motor control system treats electrically elicited tactile inputs similarly to native tactile inputs. The ability of electrically elicited tactile inputs to cause postural adjustments suggests that these inputs are incorporated into sensorimotor control, despite arising from artificial nerve stimulation. These results are encouraging for application of neural stimulation in restoring missing sensory feedback after limb loss and suggest PNS could provide an alternate method to perturb foot-sole tactile information for investigating integration of tactile feedback with other sensory modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shell, Christie, Marasco, Charkhkar and Triolo.)

This case study evaluated the effect of implanted multijoint neuromuscular electrical stimulation gait assistance on oxygen consumption relative to walking without neuromuscular electrical stimulation after stroke. The participant walked slowly with an asymmetric gait pattern after stroke. He completed repeated 6-min walk tests at a self-selected walking speed with and without hip, knee, and ankle stimulation assistance. His walking speed with neuromuscular electrical stimulation more than doubled from 0.28 ± 0.01 m/sec to 0.58 ± 0.04 m/sec, whereas average step length and cadence increased by 0.12 m and 24 steps/min, respectively. As a result, energy cost of walking with neuromuscular electrical stimulation decreased by 0.19 ml O2/kg per meter as compared with walking without stimulation while oxygen consumption increased by 1.1 metabolic equivalent of tasks (3.9 ml O2/kg per minute). These metabolic demands are similar to those reported for stroke survivors capable of walking at equivalent speeds without stimulation, suggesting the increase in oxygen consumption and decreased energy cost result from improved efficiency of faster walking facilitated by neuromuscular electrical stimulation. Although the effect of neuromuscular electrical stimulation on gait economy has implications for community walking within the user's metabolic reserves, this case study's results should be interpreted with caution and the hypothesis that multijoint neuromuscular electrical stimulation improves metabolic efficiency should be tested in a wide population of stroke survivors with varied deficits.

Spinal cord injury (SCI) often results in loss of the ability to keep the trunk erect and stable while seated. Functional neuromuscular stimulation (FNS) can cause muscles paralyzed by SCI to contract and assist with trunk stability. We have extended the results of a previously reported threshold-based controller for restoring upright posture using FNS in the sagittal plane to more challenging displacements of the trunk in the coronal plane. The system was applied to five individuals with mid-thoracic or higher SCI, and in all cases the control system successfully restored upright sitting. The potential of the control system to maintain posture in forward-sideways (diagonal) directions was also tested in three of the subjects. In all cases, the controller successfully restored posture to erect. Clinically, these results imply that a simple, threshold based control scheme can restore upright sitting from forward, lateral or diagonal leaning without a chest strap; and that removal of barriers to upper extremity interaction with the surrounding environment could potentially allow objects to be more readily retrieved from around the wheelchair. Technical performance of the system was assessed in terms of three variables: response time, recovery time and percent maximum deviation from erect. Overall response and recovery times varied widely among subjects in the coronal plane (415±213 ms and 1381±883 ms, respectively) and in the diagonal planes (530±230 ms and 1800±820 ms, respectively). Average response time was significantly lower (p < 0.05) than the recovery time in all cases. The percent maximum deviation from erect was of the order of 40% or less for 9 out of 10 cases in the coronal plane and 5 out of 6 cases in diagonal directions., Competing Interests: Declaration of Competing Interest All authors declare no competing interests in this work., (Copyright © 2020 IPEM. All rights reserved.)

Study Design: Single-subject repeated measures study., Objectives: Neuromuscular electrical stimulation (NMES) can enhance walking for people with partial paralysis from incomplete spinal cord injury (iSCI). This single-subject study documents an individual's experience who both received an experimental implanted NMES system and underwent clinical bilateral hinged total knee arthroplasty (TKA). She walked in the community with knee pain prior to either intervention. Walking performance improved with an implanted NMES system. Knee pain and instability continued to worsen over time and eventually required TKA. This study evaluates the effects of these interventions., Setting: Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland OH, USA., Methods: The differential and combined effects of NMES and hinged knee replacement were assessed in terms of walking speed, toe clearance, knee angle, and participant perceptions with and without stimulation assistance both before and after TKA., Results: The combined approach both reduced pain and restored walking ability to levels achieved prior to developing significant knee pain that prevented walking without NMES. There was an interaction effect between NMES and TKA on walking speed. Toe clearance consistently improved with stimulation assistance and TKA prevented significant knee hyperextension. The greatest impact was on endurance. Knee replacement re-enabled long distance walking with the addition of stimulation again more than doubling her maximum walking distance from 214 to 513 m., Conclusions: These data support further research of combined implantable interventions that may benefit people with iSCI. Furthermore, joint laxity and pain may not necessarily be contraindications to NMES if addressed with conventional clinical treatments.

Background: Peripheral nerve stimulation with implanted nerve cuff electrodes can restore standing, stepping and other functions to individuals with spinal cord injury (SCI). We performed the first study to evaluate the clinical electrodiagnostic changes due to electrode implantation acutely, chronic presence on the nerve peri- and post-operatively, and long-term delivery of electrical stimulation., Methods: A man with bilateral lower extremity paralysis secondary to cervical SCI sustained 5 years prior to enrollment received an implanted standing neuroprosthesis including composite flat interface nerve electrodes (C-FINEs) electrodes implanted around the proximal femoral nerves near the inguinal ligaments. Electromyography quantified neurophysiology preoperatively, intraoperatively, and through 1 year postoperatively. Stimulation charge thresholds, evoked knee extension moments, and weight distribution during standing quantified neuroprosthesis function over the same interval., Results: Femoral compound motor unit action potentials increased 31% in amplitude and 34% in area while evoked knee extension moments increased significantly (p < 0.01) by 79% over 1 year of rehabilitation with standing and quadriceps exercises. Charge thresholds were low and stable, averaging 19.7 nC ± 6.2 (SEM). Changes in saphenous nerve action potentials and needle electromyography suggested minor nerve irritation perioperatively., Conclusions: This is the first human trial reporting acute and chronic neurophysiologic changes due to application of and stimulation through nerve cuff electrodes. Electrodiagnostics indicated preserved nerve health with strengthened responses following stimulated exercise. Temporary electrodiagnostic changes suggest minor nerve irritation only intra- and peri-operatively, not continuing chronically nor impacting function. These outcomes follow implantation of a neuroprosthesis enabling standing and demonstrate the ability to safely implant electrodes on the proximal femoral nerve close to the inguinal ligament. We demonstrate the electrodiagnostic findings that can be expected from implanting nerve cuff electrodes and their time-course for resolution, potentially applicable to prostheses modulating other peripheral nerves and functions., Trial Registration: ClinicalTrials.gov NCT01923662 , retrospectively registered August 15, 2013.

The contribution of somatosensation to locomotor deficits in below-knee amputees (BKAs) has not been fully explored. Unilateral disruption of plantar sensation causes able-bodied individuals to adopt locomotor characteristics that resemble those of unilateral BKAs, suggesting that restoring somatosensation may improve locomotion for amputees. In prior studies, we demonstrated that electrically stimulating the residual nerves of amputees elicited somatosensory percepts that were felt as occurring in the missing foot. Subsequently, we developed a sensory neuroprosthesis that modulated stimulation-evoked sensation in response to interactions between the prosthesis and the environment. To characterize the impact of the sensory neuroprosthesis on locomotion, we created a novel ambulatory searching task. The task involved walking on a horizontal ladder while blindfolded, which engaged plantar sensation while minimizing visual compensation. We first compared the performance of six BKAs to 14 able-bodied controls. Able-bodied individuals demonstrated higher foot placement accuracy than BKAs, indicating that the ladder test was sensitive enough to detect locomotor deficits. When three of the original six BKAs used the sensory neuroprosthesis, the tradeoff between speed and accuracy significantly improved for two of them. This study advanced our understanding of how cutaneous plantar sensation can be used to acquire action-related information during challenging locomotor tasks.

Neural stimulation systems are often limited by rapid muscle fatigue. Selective nerve cuff electrodes can target independent yet synergistic motor unit pools (MUPs), which can be used in duty-cycle reducing stimulation paradigms to prolong joint moment output., Objective: This study investigates waveform parameters within moment-prolonging paradigms and determines strategies for their optimal implementation., Methods: Composite flat-interface nerve cuff electrodes (C-FINEs) were chronically implanted on feline proximal sciatic nerves. Cyclic stimulation tests determined effects of stimulation period and duty cycle in different MUP types. Ideal parameters were then used in duty-cycle reducing carousel stimulation. Time to 50% reduction in moment (T50), moment overshoot, and moment ripple were determined for constant, open-loop carousel, and moment feedback-controlled closed-loop carousel stimulation., Results: A stimulation period of 1 s best maintained joint moment for all MUPs. Low (25%) duty cycles consistently improved joint moment maintenance, though allowable duty cycle varied among MUPs by gross muscle and fiber type. Both open- and closed-loop carousel stimulation significantly increased T50 over constant stimulation. Closed-loop carousel significantly decreased moment overshoot over the other conditions, and significantly decreased moment ripple compared with open-loop stimulation., Conclusion: Selectivity-enabled carousel stimulation prolongs joint moment over conventional constant stimulation. Appropriate waveform parameters can be quickly determined for individual MUPs and stimulation can be controlled for additional performance improvements with this paradigm., Significance: Providing prolonged, stable joint moment and muscle output to recipients of motor neuroprostheses will improve clinical outcomes, increase independence, and positively impact quality of life.

To maintain postural stability, unilateral lower-limb amputees (LLAs) heavily rely on visual and vestibular inputs, and somatosensory cues from their intact leg to compensate for missing somatosensory information from the amputated limb. When any of these resources are compromised, LLAs exhibit poor balance control compared to able-bodied individuals. We hypothesized that restoring somatosensation related to the missing limb via direct activation of the sensory nerves in the residuum would improve the standing stability of LLAs. We developed a closed-loop sensory neuroprosthesis utilizing non-penetrating multi-contact cuff electrodes implanted around the residual nerves to elicit perceptions of the location and intensity of plantar pressures under the prosthetic feet of two transtibial amputees. Effects of the sensory neuroprosthesis on balance were quantified with the Sensory Organization Test and other posturographic measures of sway. In both participants, the sensory neuroprosthesis improved equilibrium and sway when somatosensation from the intact leg and visual inputs were perturbed simultaneously. One participant also showed improvement with the sensory neuroprosthesis whenever somatosensation in the intact leg was compromised via perturbations of the platform. These observations suggest the sensory feedback elicited by neural stimulation can significantly improve the standing stability of LLAs, particularly when other sensory inputs are depleted or otherwise compromised.

Functional neuromuscular stimulation (FNS) can be used to restore seated trunk function in individuals paralyzed due to spinal cord injury (SCI). Musculoskeletal models allow for the design and tuning of controllers for use with FNS; however, these models often use aggregated estimates for parameters of the musculotendon elements, the most significant of which is maximum isometric force (MIF). Stimulated MIF for individuals with SCI is typically assumed to be approximately 50% of the values exhibited by able-bodied muscles, which itself varies between studies and individuals. A method for estimating subject-specific MIF during dynamic motions in individuals with SCI produced by electrical stimulation has been developed to test this assumption and obtained more accurate estimates for biomechanical analysis and controller design. A simple on-off controller was applied to individuals with SCI seated in the workspace of a motion capture system to record joint angles of three types of trunk motions: forward flexion, left and right lateral bending followed by returning, un-aided, to upright posture via neural stimulation delivered to activate the muscles of the hips and trunk. System identification was used with a musculoskeletal model to find the optimal MIF values that reproduced the experimentally observed motions. Experiments with five volunteers with SCI indicate that an MIF of the 50% able-bodied values commonly used is significantly lower than the identified estimates in 33 of 44 muscle groups tested. This suggests that the strengths of paralyzed muscles when stimulated with FNS have been underestimated in many situations and their true force outputs may be higher than the values suggested for use in simulation studies with musculoskeletal models. These findings indicate that subject-specific musculoskeletal models can more closely mimic the motions of subjects by using individualized estimates of MIF, which may allow the design and tuning of controllers while reducing the time spent with subjects in the loop.

Peripheral nerve cuff electrodes (NCEs) in motor system neuroprostheses can generate strong muscle contractions and enhance surgical efficiency by accessing multiple muscles from a single proximal location. Predicting chronic performance of high contact density NCEs based on intraoperative observations would facilitate implantation at locations that maximize selective recruitment, immediate connection of optimal contacts to implanted pulse generators (IPGs) with limited output channels, and initiation of postoperative rehabilitation as soon as possible after surgery. However, the stability of NCE intraoperative recruitment to predict chronic performance has not been documented. Here we report the first-in-human application of a specific NCE, the composite flat interface nerve electrode (C-FINE), at a new and anatomically challenging location on the femoral nerve close to the inguinal ligaments. EMG and moment recruitment curves were recorded for each of the 8 contacts in 2 C-FINE intraoperatively, perioperatively, and chronically for 6 months. Intraoperative measurements predicted chronic outcomes for 87.5% of contacts with 14/16 recruiting the same muscles at 6 months as intraoperatively. In both 8-contact C-FINEs, 3 contacts elicited hip flexion and 5 selectively generated knee extension, 3 of which activated independent motor unit populations each sufficient to support standing. Recruitment order stabilized in less than 3 weeks and did not change thereafter. While confirmation of these results will be required with future studies and implant locations, this suggests that remobilization and stimulated exercise may be initiated 3 weeks after surgery with little risk of altering performance.

The purpose of this review article is to describe the underlying methodology for successfully translating novel interfaces for electrical modulation of the peripheral nervous system (PNS) from basic design concepts to clinical applications and chronic human use. Despite advances in technologies to communicate directly with the nervous system, the pathway to clinical translation for most neural interfaces is not clear. FDA guidelines provide information on necessary evidence which should be generated and submitted to allow the agency evaluate safety and efficacy of a new medical device. However, a knowledge gap exists on translating neural interfaces from pre-clinical studies into the clinical domain. Our article is intended to inform the field on some of the key considerations for such a transition process specific to neural interfaces that may not be already covered by FDA guidances. This framework focuses on non-penetrating peripheral nerve stimulating electrodes that have been proven effective for motor and sensory neural prostheses and successfully transitioned from pre-clinical through first-in-human and chronic clinical deployment. We discuss the challenges of moving these neural interfaces along the translational continuum and ultimately through FDA approval for human feasibility studies. Specifically, we describe a translational process involving: quantitative human anatomy, neural modeling and simulation, acute intraoperative testing and verification, clinical demonstration with temporary percutaneous access, and finally chronic clinical deployment and functional performance. To clarify and demonstrate the importance of each step of this translational framework, we present case studies from electrodes developed at Case Western Reserve University (CWRU), specifically the spiral cuff, the Flat Interface Nerve Electrode (FINE), and the Composite FINE (C-FINE). In addition, we demonstrate that success along this translational pathway can be further expedited by: appropriate selection of well-characterized materials, validation of fabrication and sterilization protocols, well-implemented quality control measures, and quantification of impact on neural structure, health, and function. The issues and approaches identified in this review for the peripheral nervous system may also serve to accelerate the dissemination of any new neural interface into clinical practice, and consequently advance the performance, utility, and clinical value of new neural prostheses or neuromodulation systems., (Published by Elsevier B.V.)

The perception of somatosensation requires the integration of multimodal information, yet the effects of vision and posture on somatosensory percepts elicited by neural stimulation are not well established. In this study, we applied electrical stimulation directly to the residual nerves of trans-tibial amputees to elicit sensations referred to their missing feet. We evaluated the influence of congruent and incongruent visual inputs and postural manipulations on the perceived size and location of stimulation-evoked somatosensory percepts. We found that although standing upright may cause percept size to change, congruent visual inputs and/or body posture resulted in better localization. We also observed visual capture: the location of a somatosensory percept shifted toward a visual input when vision was incongruent with stimulation-induced sensation. Visual capture did not occur when an adopted posture was incongruent with somatosensation. Our results suggest that internal model predictions based on postural manipulations reinforce perceived sensations, but do not alter them. These characterizations of multisensory integration are important for the development of somatosensory-enabled prostheses because current neural stimulation paradigms cannot replicate the afferent signals of natural tactile stimuli. Nevertheless, multisensory inputs can improve perceptual precision and highlight regions of the foot important for balance and locomotion.

Objective: Previous studies suggest that somatosensory feedback has the potential to improve the functional performance of prostheses, reduce phantom pain, and enhance embodiment of sensory-enabled prosthetic devices. To maximize such benefits for amputees, the temporal properties of the sensory feedback must resemble those of natural somatosensation in an intact limb., Approach: To better understand temporal perception of artificial sensation, we characterized the perception of visuotactile synchrony for tactile perception restored via peripheral nerve stimulation. We electrically activated nerves in the residual limbs of two trans-tibial amputees and two trans-radial amputees via non-penetrating nerve cuff electrodes, which elicited sensations referred to the missing limbs., Main Results: Our findings suggest that with respect to vision, stimulation-induced sensation has a point of subjective simultaneity (PSS; processing time) and just noticeable difference (JND; temporal sensitivity) that are similar to natural touch. The JND was not significantly different between the participants with upper- and lower-limb amputations. However, the PSS indicated that sensations evoked in the missing leg must occur significantly earlier than those in the hand to be perceived as maximally synchronous with vision. Furthermore, we examined visuotactile synchrony in the context of a functional task during which stimulation was triggered by pressure applied to the prosthesis. Stimulation-induced sensation could be delayed up to 111  ±  62 ms without the delay being reliably detected., Significance: The quantitative temporal properties of stimulation-induced perception were previously unknown and will contribute to design specifications for future sensory neuroprostheses.

Knowledge of the upper extremity (UE) effort exerted under real-world conditions is important for understanding how persons with motor or sensory disorders perform the postural shifts necessary to complete many activities of daily living while standing. To this end, a feedback controller, named the "Posture Follower Controller", was developed to aid in task-dependent posture shifting by individuals with spinal cord injury standing with functional neuromuscular stimulation. In this experimental feasibility study, the controller modulated activation to the paralyzed lower extremity muscles as a function of the position of overall center of pressure (CoP), which was prescribed to move in a straight line in forward and diagonal directions. Posture-dependent control of stimulation enabled leaning movements that translated the CoP up to 48 mm away from the nominal position during quiet standing. The mean 95% prediction ellipse area, a measure of the CoP dispersion in the forward, forward-right, and forward-left directions, was 951.0 ± 341.1 mm 2 , 1095.9 ± 251.2 mm 2 , and 1364.5 ± 688.2 mm 2 , respectively. The average width of the prediction ellipses across the three directions was 15.1 mm, indicating that the CoP deviated from the prescribed path as task-dependent postures were assumed. The average maximal UE effort required to adjust posture across all leaning directions was 24.1% body weight, which is only slightly more than twice of what is required to maintain balance in an erect standing posture. These preliminary findings suggest that stimulation can be modulated to effectively assume user-specified, task-dependent leaning postures characterized by the CoP shifts that deviate away from the nominal position and which require moderate UE effort to execute.

Objective: Sensory input in lower-limb amputees is critically important to maintaining balance, preventing falls, negotiating uneven terrain, responding to unexpected perturbations, and developing the confidence required for societal participation and public interactions in unfamiliar environments. Despite noteworthy advances in robotic prostheses for lower-limb amputees, such as microprocessor knees and powered ankles, natural somatosensory feedback from the lost limb has not yet been incorporated in current prosthetic technologies., Approach: In this work, we report eliciting somatic sensation with neural stimulation delivered by chronically-implanted, non-penetrating nerve cuff electrodes in two transtibial amputees. High-density, flexible, 16-contact nerve cuff electrodes were surgically implanted for the selective activation of sensory fascicles in the nerves of the posterior thigh above the knee. Electrical pulses at safe levels were delivered to the nerves by an external stimulator via percutaneous leads attached to the cuff electrodes., Main Results: The neural stimulation was perceived by participants as sensation originating from the missing limb. We quantitatively and qualitatively ascertained the intensity, modality as well as the location and stability of the perceived sensations. Stimulation through individual contacts within the nerve cuffs evoked repeatable sensations of various modalities and at discrete locations projected to the missing toes, foot and ankle, as well as in the residual limb. In addition, we observed a high overlap in reported locations between distal versus proximal cuffs suggesting that the same sensory responses could be elicited from more proximal points on the nerve., Significance: Based on these findings, the high-density cuff technology is suitable for restoring natural sensation to lower-limb amputees and could be utilized in developing a neuroprosthesis with natural sensory feedback. The overlap in reported locations between proximal and distal cuffs indicates that our approach might be applicable to transfemoral amputees where distal muscles and branches of sciatic nerve are not available.

Background: The leading cause of injury for manual wheelchair users are tips and falls caused by unexpected destabilizing events encountered during everyday activities. The purpose of this study was to determine the feasibility of automatically restoring seated stability to manual wheelchair users with spinal cord injury (SCI) via a threshold-based system to activate the hip and trunk muscles with electrical stimulation during potentially destabilizing events., Methods: We detected and classified potentially destabilizing sudden stops and turns with a wheelchair-mounted wireless inertial measurement unit (IMU), and then applied neural stimulation to activate the appropriate muscles to resist trunk movement and restore seated stability. After modeling and preliminary testing to determine the appropriate inertial signatures to discriminate between events and reliably trigger stimulation, the system was implemented and evaluated in real-time on manual wheelchair users with SCI. Three participants completed simulated collision events and four participants completed simulated rapid turns. Data were analyzed as a series of individual case studies with subjects acting as their own controls with and without the system active., Results: The controller achieved 93% accuracy in detecting collisions and right turns, and 100% accuracy in left turn detection. Two of the three subjects who participated in collision testing with stimulation experienced significantly decreased maximum anterior-posterior trunk angles (p < 0.05). Similar results were obtained with implanted and surface stimulation systems., Conclusions: This study demonstrates the feasibility of a neural stimulation control system based on simple inertial measurements to improve trunk stability and overall safety of people with spinal cord injuries during manual wheelchair propulsion. Further studies are required to determine clinical utility in real world situations and generalizability to the broader SCI or other population of manual or powered wheelchair users., Trial Registration: ClinicalTrials.gov Identifier NCT01474148 . Registered 11/08/2011 retrospectively registered.

Objective: Test the effect of a multi-joint control with implanted electrical stimulation on walking after spinal cord injury (SCI)., Design: Single subject research design with repeated measures., Setting: Hospital-based biomechanics laboratory and user assessment of community use., Participants: Female with C6 AIS C SCI 30 years post injury., Interventions: Lower extremity muscle activation with an implanted pulse generator and gait training., Outcome Measures: Walking speed, maximum distance, oxygen consumption, upper extremity (UE) forces, kinematics and self-assessment of technology., Results: Short distance walking speed at one-year follow up with or without stimulation was not significantly different from baseline. However, average walking speed was significantly faster (0.22 m/s) with stimulation over longer distances than volitional walking (0.12 m/s). In addition, there was a 413% increase in walking distance from 95 m volitionally to 488 m with stimulation while oxygen consumption and maximum upper extremity forces decreased by 22 and 16%, respectively. Stimulation also produced significant (P ≤ 0.001) improvements in peak hip and knee flexion, ankle angle at foot off and at mid-swing., Conclusion: An implanted neuroprosthesis enabled a subject with incomplete SCI to walk longer distances with improved hip and knee flexion and ankle dorsiflexion resulting in decreased oxygen consumption and UE support. Further research is required to determine the robustness, generalizability and functional implications of implanted neuroprostheses for community ambulation after incomplete SCI.

Objective: To quantify the long-term (>2y) effects of lower extremity (LE) neuroprostheses (NPs) for standing, transfers, stepping, and seated stability after spinal cord injury., Design: Single-subject design case series with participants acting as their own concurrent controls, including retrospective data review., Setting: Hospital-based clinical biomechanics laboratory with experienced (>20y in the field) research biomedical engineers, a physical therapist, and medical monitoring review., Participants: Long-term (6.2±2.7y) at-home users (N=22; 19 men, 3 women) of implanted NPs for trunk and LE function with chronic (14.4±7.1y) spinal cord injury resulting in full or partial paralysis., Interventions: Technical and clinical performance measurements, along with user satisfaction surveys., Main Outcome Measures: Knee extension moment, maximum standing time, body weight supported by lower extremities, 3 functional standing tasks, 2 satisfaction surveys, NP usage, and stability of implanted components., Results: Stimulated knee extension strength and functional capabilities were maintained, with 94% of implant recipients reporting being very or moderately satisfied with their system. More than half (60%) of the participants were still using their implanted NPs for exercise and function for >10min/d on nearly half or more of the days monitored; however, maximum standing times and percentage body weight through LEs decreased slightly over the follow-up interval. Stimulus thresholds were uniformly stable. Six-year survival rates for the first-generation implanted pulse generator (IPG) and epimysial electrodes were close to 90%, whereas those for the second-generation IPG along with the intramuscular and nerve cuff electrodes were >98%., Conclusions: Objective and subjective measures of the technical and clinical performances of implanted LE NPs generally remained consistent for 22 participants after an average of 6 years of unsupervised use at home. These findings suggest that implanted LE NPs can provide lasting benefits that recipients value., (Published by Elsevier Inc.)

This study systematically explored the potential of applying feedback control of functional neuromuscular stimulation (FNS) for stabilizing various erect and leaning standing postures after spinal cord injury (SCI). Perturbations ranging from 2 to 6% body weight were applied to two subjects with motor complete thoracic level SCI who were proficient at standing with implanted multichannel neural stimulators to activate the ankle, knee, hip and trunk muscles. The subjects stood with four different postures: erect, forward, forward-right and forward-left. Repeatable and controlled perturbations were applied in the forward, backward, rightward and leftward directions by linear actuators pulling on ropes attached to the subjects via a belt worn just above the waist. Upper extremity (UE) forces exerted on a stationary walker were measured with load cells attached to the handles. A feedback controller based on center of pressure (CoP) varied the stimulation levels to the otherwise paralyzed muscles so as to resist the effects of the perturbations. The effect of the feedback controller was compared to the case where only open-loop baseline stimulation was applied. This was done in terms of: (a) maximum resultant UE force exerted by the subjects on the walker, (b) maximum resultant CoP overshoot and (c) CoP root-mean-square deviation (RMSD). Feedback control resulted in significant reductions in the mean values of the majority of outcome values compared to baseline open-loop stimulation. Maximum resultant UE force was reduced by as much as 50% in one of the postures for one of the subjects. RMSD and maximum CoPs were reduced by as much as 75 and 70%, respectively, with feedback control. These results indicate that feedback control can be used to reject destabilizing disturbances in individuals with SCI using FNS not only for erect postures but also for leaning postures typically adopted during reaching while attempting various activities of daily living.

A patient with multiple sclerosis-related gait dysfunction was followed over the course of his disease. Despite aggressive treatment, he developed significant weakness in ankle dorsiflexors and hip and knee flexors and was no longer capable of consistently taking a step on his own. With electrical stimulation of hip and knee flexors and ankle dorsiflexors using implanted electrodes, he was able to consistently walk short distances as far as 30 m, thus significantly improving his Expanded Disability Status Scale score. This case study supports further exploration into the potential benefits of an implanted pulse generator to ameliorate gait dysfunction and improve quality of life for people with multiple sclerosis.

An important consideration in the design of a practical system to restore walking in individuals with spinal cord injury is to minimize metabolic energy demand on the user. In this study, the effects of exoskeletal constraints on metabolic energy expenditure were evaluated in able-bodied volunteers to gain insight into the demands of walking with a hybrid neuroprosthesis after paralysis. The exoskeleton had a hydraulic mechanism to reciprocally couple hip flexion and extension, unlocked hydraulic stance controlled knee mechanisms, and ankles fixed at neutral by ankle-foot orthoses. These mechanisms added passive resistance to the hip (15 Nm) and knee (6 Nm) joints while the exoskeleton constrained joint motion to the sagittal plane. The average oxygen consumption when walking with the exoskeleton was 22.5 ± 3.4 ml O2/min/kg as compared to 11.7 ± 2.0 ml O2/min/kg when walking without the exoskeleton at a comparable speed. The heart rate and physiological cost index with the exoskeleton were at least 30% and 4.3 times higher, respectively, than walking without it. The maximum average speed achieved with the exoskeleton was 1.2 ± 0.2 m/s, at a cadence of 104 ± 11 steps/min, and step length of 70 ± 7 cm. Average peak hip joint angles (25 ± 7°) were within normal range, while average peak knee joint angles (40 ± 8°) were less than normal. Both hip and knee angular velocities were reduced with the exoskeleton as compared to normal. While the walking speed achieved with the exoskeleton could be sufficient for community ambulation, metabolic energy expenditure was significantly increased and unsustainable for such activities. This suggests that passive resistance, constraining leg motion to the sagittal plane, reciprocally coupling the hip joints, and weight of exoskeleton place considerable limitations on the utility of the device and need to be minimized in future designs of practical hybrid neuroprostheses for walking after paraplegia.

Background: Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation., Methods: Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations., Results: In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation., Conclusions: The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option for long-term clinical use on human peripheral nerves in implanted neuroprostheses.

Background: Implanted motor system neuroprostheses can be effective at increasing personal mobility of persons paralyzed by spinal cord injuries. However, currently available neural stimulation systems for standing employ patterns of constant activation and are unreactive to changing postural demands., Methods: In this work, we developed a closed-loop controller for detecting forward-directed body disturbances and initiating a stabilizing step in a person with spinal cord injury. Forward-directed pulls at the waist were detected with three body-mounted triaxial accelerometers. A finite state machine was designed and tested to trigger a postural response and apply stimulation to appropriate muscles so as to produce a protective step when the simplified jerk signal exceeded predetermined thresholds., Results: The controller effectively initiated steps for all perturbations with magnitude between 10 and 17.5 s body weight, and initiated a postural response with occasional steps at 5% body weight. For perturbations at 15 and 17.5% body weight, the dynamic responses of the subject exhibited very similar component time periods when compared with able-bodied subjects undergoing similar postural perturbations. Additionally, the reactive step occurred faster for stronger perturbations than for weaker ones (p < .005, unequal varience t-test.) CONCLUSIONS: This research marks progress towards a controller which can improve the safety and independence of persons with spinal cord injury using implanted neuroprostheses for standing.

Objective: As neural interfaces demonstrate success in chronic applications, a novel class of reshaping electrodes with patterned regions of stiffness will enable application to a widening range of anatomical locations. Patterning stiff regions and flexible regions of the electrode enables nerve reshaping while accommodating anatomical constraints of various implant locations ranging from peripheral nerves to spinal and autonomic plexi., Approach: Introduced is a new composite electrode enabling patterning of regions of various electrode mechanical properties. The initial demonstration of the composite's capability is the composite flat interface nerve electrode (C-FINE). The C-FINE is constructed from a sandwich of patterned PEEK within layers of pliable silicone. The shape of the PEEK provides a desired pattern of stiffness: stiff across the width of the nerve to reshape the nerve, but flexible along its length to allow for bending with the nerve. This is particularly important in anatomical locations near joints or organs, and in constrained compartments. We tested pressure and volume design constraints in vitro to verify that the C-FINE can attain a safe cuff-to-nerve ratio (CNR) without impeding intraneural blood flow. We measured nerve function as well as nerve and axonal morphology following 3 month implantation of the C-FINE without wires on feline peripheral nerves in anatomically constrained areas near mobile joints and major blood vessels in both the hind and fore limbs., Main Results: In vitro inflation tests showed effective CNRs (1.93  ±  0.06) that exceeded the industry safety standard of 1.5 at an internal pressure of 20 mmHg. This is less than the 30 mmHg shown to induce loss of conduction or compromise blood flow. Implanted cats showed no changes in physiology or electrophysiology. Behavioral signs were normal suggesting healthy nerves. Motor nerve conduction velocity and compound motor action potential did not change significantly between implant and explant (p  >  0.15 for all measures). Axonal density and myelin sheath thickness was not significantly different within the electrode compared to sections greater than 2 cm proximal to implanted cuffs (p  >  0.14 for all measures)., Significance: We present the design and verification of a novel nerve cuff electrode, the C-FINE. Laminar manufacturing processes allow C-FINE stiffness to be configured for specific applications. Here, the central region in the configuration tested is stiff to reshape or conform to the target nerve, while edges are highly flexible to bend along its length. The C-FINE occupies less volume than other NCEs, making it suitable for implantation in highly mobile locations near joints. Design constraints during simulated transient swelling were verified in vitro. Maintenance of nerve health in various challenging anatomical locations (sciatic and median/ulnar nerves) was verified in a chronic feline model in vivo.