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An active probe and microstimulator SoC for interfacing with peripheral nerves is presented. It performs 64-channel artifact-tolerant neural recording, cuff imbalance compensation by impedance sensing, and neurostimulation for the closed-loop operation. Each recording channel is a second-order opamp-less $\Delta \Sigma $ ADC that consumes 140 nW and occupies 0.01 mm2 area in 130 nm CMOS. The single-loop $\Delta \Sigma $ architecture achieves second-order noise shaping with two passive integrators. To the best of our knowledge, this yields the lowest power and area of any second-order $\Delta \Sigma $ ADC and the lowest FOM (fJ/conv. step) of any passive second-order $\Delta \Sigma $ ADC (27 fJ/conv. step). The SoC uniquely performs multi-modal input signal recording: voltage (for neural recording) and current (for impedance sensing) are measured concurrently using frequency multiplexing. The SoC also features a 60 MHz energy-efficient inductive powering link and a 600 MHz RF data communication link. The prototype is validated in vivo in the rat sciatic nerve for electroneurogram (ENG) sensing and the correction of impedance-imbalance in cuff electrodes.

With the development of newer techniques for symptomatic neuroma treatment, such as regenerative peripheral nerve interface and targeted muscle reinnervation, transposition and coverage techniques often have been referred to as "passive techniques." In spite of its negative connotation, these passive techniques yield positive results in a majority of patients treated. The experienced surgeon has more options than ever before in the prevention and management of problematic neuromas. Critical appraisal of the current literature reveals no single, optimal standard of care. Instead, surgeons have a plethora of useful techniques that can be implemented on a case-by-case basis to optimize outcomes.

The quest to find the ideal prosthetic device interface that enables intuitive control has motivated several recent innovations. Although current prosthetic device control strategies have advanced the field of neuroprosthetic control, they are limited in their ability to generate reliable, stable, and specific signals to replicate the complex movements of the upper extremity. The regenerative peripheral nerve interface (RPNI) is a promising solution to enhance prosthetic device control. This article describes the development of RPNIs and summarizes its successful use in the control of advanced prosthetic devices in patients with upper extremity amputations.

A considerable number of major limb amputation patients will develop symptomatic neuromas within the residual limb. There has been a paradigm shift in the surgical treatment of symptomatic neuromas from techniques that attempt to interrupt axonal regeneration in favor of techniques that permit reinnervation. In addition, growing evidence suggests that successful treatment of peripheral nerve pain may diminish the development of phantom limb pain. We discuss novel surgical techniques that seek to prevent neuroma formation and in turn reduce phantom limb pain. Targeted muscle reinnervation and regenerative peripheral nerve interface surgery provide regenerating peripheral nerves denervated targets for reinnervation thus reducing the number of free axons available to form neuromas. While very different in technique, both approaches decrease the formation of symptomatic neuromas. In doing so, these methods reduce the experience of residual limb pain and phantom limb pain. Implementation of innovative surgical techniques after peripheral nerve transection can transform the management of postamputation pain. Decreasing the impact of neuroma pain and phantom limb pain will facilitate prosthetic rehabilitation, decrease analgesic use, and improve quality of life after limb amputation.

Peripheral nerve interfaces are frequently used in experimental neuroscience and regenerative medicine for a wide variety of applications. Such interfaces can be sensors, actuators, or both. Traditional methods of peripheral nerve interfacing must either tether to an external system or rely on battery power that limits the time frame for operation. With recent developments of wireless, battery-free, and fully implantable peripheral nerve interfaces, a new class of devices can offer capabilities that match or exceed those of their wired or battery-powered precursors. This paper describes methods to (i) surgically implant and (ii) wirelessly power and control this system in adult rats. The sciatic and phrenic nerve models were selected as examples to highlight the versatility of this approach. The paper shows how the peripheral nerve interface can evoke compound muscle action potentials (CMAPs), deliver a therapeutic electrical stimulation protocol, and incorporate a conduit for the repair of peripheral nerve injury. Such devices offer expanded treatment options for single-dose or repeated dose therapeutic stimulation and can be adapted to a variety of nerve locations.

BACKGROUND Postamputation pain affects a large number of individuals living with major limb loss. Regenerative peripheral nerve interfaces are constructs composed of a transected peripheral nerve implanted into an autologous free muscle graft. The authors have previously shown that regenerative peripheral nerve interfaces can be used to treat symptomatic end neuromas that develop after major limb amputation. In this study, they investigated the potential of prophylactic interfaces to prevent the formation of symptomatic neuromas and mitigate phantom limb pain. METHODS Patients who underwent limb amputation with and without prophylactic regenerative peripheral nerve interface implantation were identified. A retrospective review was performed to ascertain patient demographics, level of amputation, and postoperative complications. Documentation of symptomatic neuromas and phantom limb pain was noted. RESULTS Postoperative outcomes were evaluated in a total of 90 patients. Forty-five patients underwent interface implantation at the time of primary amputation, and 45 control patients underwent amputation without interfaces. Six control patients (13.3 percent) developed symptomatic neuromas in the postoperative period compared with zero (0.0 percent) in the prophylactic interface group (p = 0.026). Twenty-three interface patients (51.1 percent) reported phantom limb pain, compared with 41 control patients (91.1 percent; p < 0.0001). CONCLUSIONS Prophylactic regenerative peripheral nerve interfaces in major limb amputees resulted in a lower incidence of both symptomatic neuromas and phantom limb pain compared with control patients undergoing amputation without regenerative peripheral nerve interfaces, suggesting that prevention of peripheral neuromas following amputation may diminish the central pain mechanisms that lead to phantom limb pain. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

Objectives Kilohertz high-frequency alternating current (KHFAC) electrical nerve stimulation produces a reversible nerve block in peripheral nerves in human patients with chronic pain pathologies. Although this stimulation methodology has been verified with nonselective extrafascicular electrodes, the effectiveness of producing a selective nerve block with more-selective intrafascicular electrodes has not been well documented. The objective of this study was to examine whether intrafascicular electrodes can block painful stimuli while preserving conduction of other neural activity within the implanted nerve. Materials and methods We analyzed the effects of various stimulation waveforms delivered through Utah Slanted Electrode Arrays (USEAs) implanted in the median nerve of a male human subject with a left brachial plexus injury. We compared KHFAC stimulation with a sham control. Results KHFAC stimulation through USEA electrodes produced a reduction in pain sensitivity in the palmar aspect of the left middle finger. KHFAC had limited effects on the patient's ability to feel tactile probing in the same area or move the digits of his left hand. Other tested stimulation parameters either increased or showed no reduction in pain. Conclusions KHFAC stimulation in peripheral nerves through intrafascicular electrodes demonstrated a selective reduction in pain sensitivity while preserving other nerve functions. This treatment may benefit patient populations who have chronic pain originating from peripheral nerves, but who do not want to block whole-nerve function in order to preserve sensory and motor function reliant on the implanted nerve. Furthermore, KHFAC may benefit patients who respond negatively to other forms of peripheral nerve stimulation therapy.

Chronic pain is a significant health care problem. Many patients' pain can be linked to a neuropathic origin, diagnosed with a thorough history and physical examination, and confirmed with a diagnostic nerve block. There are new procedures designed to address neuropathic pain from symptomatic neuromas by providing physiologic targets for regenerating axons following neurectomy. Dermal wrapping of the end of a sensory nerve following transection, a technique called dermatosensory peripheral nerve interface, may provide an optimal environment to prevent neuroma pain and reduce chronic neuropathic pain.

Background. Robotic exoskeleton devices have become a promising modality for restoration of extremity function in individuals with limb loss or functional weakness. However, there exists no consistent or reliable way to record efferent motor action potentials from intact peripheral nerves to control device movement. Peripheral nerve motor action potentials are similar in amplitude to that of background noise, producing an unfavorable signal-to-noise ratio (SNR) that makes these signals difficult to detect and interpret. To address this issue, we have developed the muscle cuff regenerative peripheral nerve interface (MC-RPNI), a construct consisting of a free skeletal muscle graft wrapped circumferentially around an intact peripheral nerve. Over time, the muscle graft regenerates, and the intact nerve undergoes collateral axonal sprouting to reinnervate the muscle. The MC-RPNI amplifies efferent motor action potentials by several magnitudes, thereby increasing the SNR, allowing for higher fidelity signaling and detection of motor intention. The goal of this study was to characterize the signaling capabilities and viability of the MC-RPNI over time.Methods. Thirty-seven rats were randomly assigned to one of five experimental groups (Groups A-E). For MC-RPNI animals, their contralateral extensor digitorum longus (EDL) muscle was harvested and trimmed to either 8 mm (Group A) or 13 mm (Group B) in length, wrapped circumferentially around the intact ipsilateral common peroneal (CP) nerve, secured, and allowed to heal for 3 months. Additionally, one 8 mm (Group C) and one 13 mm (Group D) length group had an epineurial window created in the CP nerve immediately preceding MC-RPNI creation. Group E consisted of sham surgery animals. At 3 months, electrophysiologic analyses were conducted to determine the signaling capabilities of the MC-RPNI. Additionally, electromyography and isometric force analyses were performed on the CP-innervated EDL to determine the effects of the MC-RPNI on end organ function. Following evaluation, the CP nerve, MC-RPNI, and ipsilateral EDL muscle were harvested for histomorphometric analysis.Results. Study endpoint analysis was performed at 3 months post-surgery. All rats displayed visible muscle contractions in both the MC-RPNI and EDL following proximal CP nerve stimulation. Compound muscle action potentials were recorded from the MC-RPNI following proximal CP nerve stimulation and ranged from 3.67 ± 0.58 mV to 6.04 ± 1.01 mV, providing efferent motor action potential amplification of 10-20 times that of a normal physiologic nerve action potential. Maximum tetanic isometric force (Fo) testing of the distally-innervated EDL muscle in MC-RPNI groups producedFo(2341 ± 114 mN-2832 ± 102 mN) similar to controls (2497 ± 122 mN), thus demonstrating that creation of MC-RPNIs did not adversely impact the function of the distally-innervated EDL muscle. Overall, comparison between all MC-RPNI sub-groups did not reveal any statistically significant differences in signaling capabilities or negative effects on distal-innervated muscle function as compared to the control group.Conclusions. MC-RPNIs have the capability to provide efferent motor action potential amplification from intact nerves without adversely impacting distal muscle function. Neither the size of the muscle graft nor the presence of an epineurial window in the nerve had any significant impact on the ability of the MC-RPNI to amplify efferent motor action potentials from intact nerves. These results support the potential for the MC-RPNI to serve as a biologic nerve interface to control advanced exoskeleton devices.

Summary. Nerve transection injuries can result in painful neuromas that adversely affect patient recovery. This is especially significant following amputation surgeries in the setting of prosthetic wear and function. Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface (RPNI) are 2 modern surgical techniques that provide neuromuscular targets for these transected nerve endings to reinnervate. These strategies have been previously shown to reduce phantom limb pain, residual limb pain, and neuroma-related pain.1,2,7,11 Two recent articles described technical adaptations of combining targeted muscle reinnervation and RPNI to create a hybrid procedure.3,12 In this article, we propose a different modification of targeted muscle reinnervation and RPNI, where the transected nerve stump is coapted to a recipient unit consisting of an intact distal nerve branch with its associated muscle graft. We called this recipient unit a targeted peripheral nerve interface because it contains a distal nerve branch for nerve coaptation and can guide axonal regeneration from the donor nerve to its target muscle graft. We theorize that targeted peripheral nerve interface may lead to more even distribution of regenerating axons with potentially less pain and stronger signals for prosthetic control when compared with standard RPNI.

Over 185,000 limb amputations are performed in the United States annually, many of which are due to the sequelae of peripheral vascular disease. Symptomatic neuromas remain a significant source of postamputation morbidity and contribute to both phantom limb (PLP) and residual limb pain (RLP). While many interventions have been proposed for the treatment of symptomatic neuromas, conventional methods lead to a high incidence of neuroma recurrence. Furthermore, these existing methods do not facilitate an ability to properly interface with myoelectric prosthetic devices. The Regenerative Peripheral Nerve Interface (RPNI) was developed to overcome these limitations. The RPNI consists of an autologous free muscle graft secured around the end of a transected nerve. The muscle graft provides regenerating axons with end organs to reinnervate, thereby preventing neuroma formation. We have shown that this simple, reproducible, and safe surgical technique successfully treats and prevents neuroma formation in major limb amputations. In this paper, we describe RPNI surgery in the setting of major limb amputation and highlight the promising results of RPNIs in our animal and clinical studies.

Previous literature shows that deep learning is an effective tool to decode the motor intent from neural signals obtained from different parts of the nervous system. However, deep neural networks are often computationally complex and not feasible to work in real-time. Here we investigate different approaches' advantages and disadvantages to enhance the deep learning-based motor decoding paradigm's efficiency and inform its future implementation in real-time. Our data are recorded from the amputee's residual peripheral nerves. While the primary analysis is offline, the nerve data is cut using a sliding window to create a “pseudo-online” dataset that resembles the conditions in a real-time paradigm. First, a comprehensive collection of feature extraction techniques is applied to reduce the input data dimensionality, which later helps substantially lower the motor decoder's complexity, making it feasible for translation to a real-time paradigm. Next, we investigate two different strategies for deploying deep learning models: a one-step (1S) approach when big input data are available and a two-step (2S) when input data are limited. This research predicts five individual finger movements and four combinations of the fingers. The 1S approach using a recurrent neural network (RNN) to concurrently predict all fingers' trajectories generally gives better prediction results than all the machine learning algorithms that do the same task. This result reaffirms that deep learning is more advantageous than classic machine learning methods for handling a large dataset. However, when training on a smaller input data set in the 2S approach, which includes a classification stage to identify active fingers before predicting their trajectories, machine learning techniques offer a simpler implementation while ensuring comparably good decoding outcomes to the deep learning ones. In the classification step, either machine learning or deep learning models achieve the accuracy and F1 score of 0.99. Thanks to the classification step, in the regression step, both types of models result in a comparable mean squared error (MSE) and variance accounted for (VAF) scores as those of the 1S approach. Our study outlines the trade-offs to inform the future implementation of real-time, low-latency, and high accuracy deep learning-based motor decoder for clinical applications.

ObjectiveWe explore the long-term performance and stability of seven percutanous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human amputees as a means to permanently restore sensorimotor function after upper-limb.ApproachWe quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio of USEA and iEMG recordings and quantify the stimulation amplitude necessary to evoke detectable sensory percepts. Furthermore, we quantify the consistency of the sensory modality, receptive field location, and receptive field size of USEA-evoked percepts.Main ResultsIn the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 days (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs the number of functional recording electrodes decreased within the first two months after implantation. The signal-to-noise ratio of neural recordings and electromyographic recordings stayed relatively consistent over time. Sensory percepts were consistently evoked over the span of 14 months, were not significantly different in size, and highlighted the nerves’ fascicular organization. The percentage of percepts with consistent modality or consistent receptive field location between sessions (~1 month apart) varied between 0–86.2% and 9.1–100%, respectively. Stimulation thresholds and electrode impedances increased initially but then remained relatively stable over time.SignificanceThis work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. Although USEAs provide a rich repertoire of neural recordings and sensory percepts, performance still generally declines over time. Future work should leverage the results presented here to further improve USEA design or to develop adaptive algorithms that can maintain a high level of performance.

Introduction Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. Methods Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. Results Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). Conclusion EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control. Electronic supplementary material The online version of this article (10.1186/s12984-018-0452-1) contains supplementary material, which is available to authorized users.

Purpose: Exoskeletons have become a promising device to restore extremity function to those with limb weakness. However, these devices have not become widely adopted due to the inadequacy of current nerve interfacing methods. The Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI) was developed as a potential solution to this problem. Consisting of a segment of autologous free muscle secured around an intact nerve, the MC-RPNI is able to regenerate and reinnervate, amplifying its contained nerve’s signals through generation of EMG signals. These amplified, high-fidelity signals can then be used to intuitively and accurately control exoskeletons. The purpose of this study was to characterize MC-RPNI physiologic signaling during volitional behavior and determine long-term effects on the associated nerve. Methods: Eighteen rats were randomly assigned to one of three groups: (1) sham surgery/control; (2) nerve transection; and (3) MC-RPNI. MC-RPNIs were surgically fabricated by wrapping isogenic donor muscle graft circumferentially around the common peroneal (CP) nerve. At six months, CP nerve cuff electrodes were implanted in Groups 1 and 2,and patch electrodes were placed on all MC-RPNIs. Gait analysis and electrophysiological evaluations were performed the following day. Rats were trained to walk on a treadmill, and electrode recordings were obtained and correlated with gait videocapture. All rats had their proximal CP nerve stimulated, with efferent signals obtained at (1) downstream nerve (CSNAP), (2) MC-RPNI (CMAP), and (3) downstream-innervated extensor digitorum longus (EDL) muscle (CMAP). EDL muscle force testing was also performed following stimulation of the CP nerve. Results: All MC-RPNIs remained viable and demonstrated appropriate regeneration, revascularization, and reinnervation on histology. The MC-RPNI was found to generate large-amplitude CMAPs (2.77+/-0.926mV), amplifying its associated nerve’s signal (50.5+/-8.18µV) over 50-fold on average. The MC-RPNI was not found to affect muscle function when evaluating downstream-innervated EDL CMAPs (control: 13.4+/-2.33mV vs MC-RPNI: 14.1+/-1.44mV) or maximal twitch force (control: 562+/-70.8mN vs MC-RPNI: 653+/-34.6mN). On gait analysis, recordings from the MC-RPNI correlated with the toe-off phase of gait; for the control groups, nerve signaling could not be differentiated from background noise. When comparing MC-RPNI to control animal gait, no significant differences were noted on qualitative or joint-angle analysis. Conclusion: The MC-RPNI has the ability to chronically amplify physiologic nerve signals from intact peripheral nerves by several magnitudes while avoiding functional impairment of downstream-innervated muscle. This amplification has the capability to facilitate high accuracy detection of motor intent in order to intuitively and reliably control advanced exoskeleton devices.

Symptomatic neuromas are a common cause of postamputation pain that can lead to significant disability. Regenerative peripheral nerve interface surgery is performed to treat symptomatic neuromas and prevent the development of neuromas. This review delineates the clinical problem of postamputation pain, describes the limitations of the available treatment methods, and highlights the need for an effective treatment strategy that leverages the biologic processes of nerve regeneration and muscle reinnervation. The evidence supporting use of regenerative peripheral nerve interface surgery to mitigate neuroma formation is discussed and the rationale behind the efficacy of regenerative peripheral nerve interfaces is explored.

Summary:. Painful neuromas result from traumatic injuries of the hand and digits and cause substantial physical disability, psychological distress, and decreased quality of life among affected patients. The regenerative peripheral nerve interface (RPNI) is a novel surgical technique that involves implanting the divided end of a peripheral nerve into a free muscle graft for the purposes of mitigating neuroma formation and facilitating prosthetic limb control. The RPNI is effective in treating and preventing neuroma pain in major extremity amputations. The purpose of this study was to determine if RPNIs can be used to effectively treat neuroma pain following partial hand and digital amputations. We retrospectively reviewed the use of RPNI to treat symptomatic hand and digital neuromas at our institutions. Between November 2014 and July 2019, we performed 30 therapeutic RPNIs on 14 symptomatic neuroma patients. The average patient follow-up was 37 weeks (6–128 weeks); 85% of patients were pain-free or considerably improved at the last office visit. The RPNI can serve as a safe and effective surgical solution to treat symptomatic neuromas after hand trauma.

BACKGROUND: Biomimetic hydrogels used in tissue engineering can improve tissue regeneration and enable targeted cellular behavior; there is growing interest in combining hydrogels with microelectronics to create new neural interface platforms to help patient populations. However, effective processes must be developed to successfully integrate flexible but relatively stiff (e.g., 1–10 GPa) microelectronic arrays within soft (e.g., 1–10 kPa) hydrogels. NEW METHOD: Here, a novel method for integrating polyimide microelectrode arrays within a biomimetic hydrogel scaffold is demonstrated for use as a tissue-engineered electronic nerve interface (TEENI). Tygon tubing and a series of 3D printed molds were used to facilitate hydrogel fabrication and implantable device assembly. COMPARISON WITH EXISTING METHODS: Other comparable regenerative peripheral nerve interface technologies do not utilize the flexible microelectrode array design nor the hydrogel scaffold described here. These methods typically use stiff electrode arrays that are affixed to a similarly stiff implantable tube serving as the nerve guidance conduit. RESULTS: Our results indicate that there is a substantial mechanical mismatch between the flexible microelectronic arrays and the soft hydrogel. However, using the methods described here, there is consistent fabrication of these regenerative peripheral nerve interfaces suitable for implantation. CONCLUSIONS: The assembly process that was developed resulted in repeatable and consistent integration of microelectode arrays within a soft tissue-engineered hydrogel. As reported elsewhere, these devices have been successfully implanted in a rat sciatic nerve model and yielded neural recordings. This process can be adapted for other applications and hydrogels in which flexible electronic materials are combined with soft regenerative scaffolds.

Background Peripheral nerve interfacing has many applications ranging from investigation of neural signals to therapeutic intervention for varied diseases. This need has driven technological advancements in the field of electrode arrays and wireless systems for in-vivo electrophysiological experiments. Hence we present our fully implantable, programmable miniaturized wireless stimulation and recording devices. New method The method consists of technological advancements enabling implantable wireless recording up to 128 channels with a sampling rate of 50Khz and stimulation up to ±4 mA from 15 independent channels. The novelty of the technique consists of induction charging cages which enables freely moving small animals to undergo continuous electrophysiological and behavioral studies without any impediments. The biocompatible hermetic packaging technology for implantable capsules ensures stability for long-term chronic studies. Results Electromyographs wirelessly recorded from leg muscles of a macaque and a rat using implantable technology are presented during different behavioral task studies. The device's simultaneous stimulation and recording capabilities are reported when interfaced with the vagus and pelvic nerves. Comparison with existing method(s) The wireless interfacing technology has a large number of recording and stimulating channels without compromising on the signal quality due to sampling rates or stimulating current output capabilities. The induction charging technology along with transceiver and software interface allows experiments on multiple animals to be carried out simultaneously. Conclusions This customizable technology using wireless power transmission, reduced battery size, and miniaturized electronics has paved way for a robust, fully implantable, hermetic neural interface system enabling the study of bioelectronic medical therapies.

Background High-resolution peripheral nerve interfaces (PNIs) can provide amputees with intuitive motor control and sensory feedback. Current PNIs are limited by early device failure and suboptimal long-term stability. The present study aims to incorporate functional assessment into an in vivo test platform to assess the long-term safety and performance of PNIs for recording and stimulation. New methods Utah electrode arrays (EA) were implanted in the rat sciatic nerve along with electromyography wires in the gastrocnemius and tibialis anterior. Cranial EEG screws were implanted in the somatosensory cortex for 12 weeks. Spontaneous neural activity was recorded using the implanted EA and stimulation-induced activity was monitored throughout the experiment. The impedance of each electrode was measured, and nerve function tests were conducted throughout the EA lifetime. Post-hoc safety assessments included scanning electron microscopy (SEM) of the EA and nerve histomorphometric analysis. Results EA recordings were stable, and stimulation with EA elicited somatosensory evoked potentials and muscle contractions. Motor and sensory function tests indicated minimal deficits. Histomorphometric analysis indicated changes in nerve microstructure. SEM indicated EA-tip fracture, while lead wire breakage primarily caused device failure. Comparison with existing methods We improved our prior platform with the addition of functional assessments of sensory pathways, a robust EMG array design to increase device longevity, and quantitative analysis of nerve microstructure. Conclusion We present a test platform for long-term assessment of peripheral nerve interfaces for stimulation and recording. Using this platform, we demonstrate recording and stimulation with minimal impact on nerve function, while EA lead wire breakage and tip fracture could limit long-term device use.

Purpose: Although advanced prosthetic devices have the potential to allow fine-motor movements and extract somatosensory signals via sensitive pressure sensors, an ideal interface to integrate the human nervous system with the prosthetic doesn’t exist. Furthermore, the requirement for the implantation of indwelling electrodes and prohibitive costs limits the application of current technologies. The Regenerative Peripheral Nerve Interface (RPNI) was developed as a stable biologic interface on the notion of providing physiologic end-organ targets for regenerating axons by implantation of a residual nerve into an autogenous free muscle graft. Despite providing intuitive motor control, RPNI sensory feedback is limited and also relies on implantable electrodes for myoelectric signal transmission. To address these challenges, we investigated the placement of RPNIs underneath the defatted skin in rats to capture myoelectric signals using surface electrodes. This strategy simultaneously provides sensory feedback through the sensory reinnervation of the overlying skin. Methods: Utilizing six male F344 rats, the right tibial nerve was transected distally in the thigh before entering the leg’s posterior compartment. Subsequently, the left side extensor digitorum longus (EDL) muscle was harvested and co-apted with the proximal segment of the tibial nerve for RPNI fabrication. The RPNI was placed and secured in between the biceps femoris muscle near the skin while the side opposite to the nerve coaptation was facing the dermis. The overlying skin was defatted and fixed on top of the superficial RPNI (S-RPNI). At two months post-surgery, functional motor reinnervation was evaluated by electrical stimulation of the tibial nerve and compound muscle action potentials (CMAPs) were recorded using surface electrodes. Sensory feedback was assessed by electrical and mechanical stimulation of the skin to respectively record sensory nerve action potentials (SNAPs) and sensory afferent signals. The S-RPNI construct and its overlying skin were subsequently harvested and processed for immunohistochemistry and whole-mount immunostaining. Results: Recording muscle CMAPs from the skin was readily feasible in all animals, showing robust signals with minimal noise distortion (366 µV ± 86.3). Electrical stimulation of the skin on the lateral thigh, which is not innervated by the tibial nerve normally, resulted in classic tri-phasic SNAP generation in this nerve. Brushing the overlying skin using a cotton swab generated synchronized monomorphic afferent signals. Sensory reinnervation of the skin was shown using IHC. Whole-mount staining of the muscle component showed regenerated muscle with new neuromuscular junctions (NMJs) and spatial segregation of sensory fibers toward their end-target organ. Conclusion: Superficially placed RPNI is a viable and an alternate methodology that is simple to implicate and has the potential to transmit simultaneous, real-time, and independent sensory and motor signals between the residual nerve and the prostheses.

ObjectiveWhile prosthetic hands with independently actuated digits have become commercially available, state-of-the-art human-machine interfaces (HMI) only permit control over a limited set of grasp patterns, which does not enable amputees to experience sufficient improvement in their daily activities to make an active prosthesis useful.ApproachHere we present a technology platform combining fully-integrated bioelectronics, implantable intrafascicular microelectrodes and deep learning-based artificial intelligence (AI) to facilitate this missing bridge by tapping into the intricate motor control signals of peripheral nerves. The bioelectric neural interface includes an ultra-low-noise neural recording system to sense electroneurography (ENG) signals from microelectrode arrays implanted in the residual nerves, and AI models employing the recurrent neural network (RNN) architecture to decode the subject’s motor intention.Main resultsA pilot human study has been carried out on a transradial amputee. We demonstrate that the information channel established by the proposed neural interface is sufficient to provide high accuracy control of a prosthetic hand up to 15 degrees of freedom (DOF). The interface is intuitive as it directly maps complex prosthesis movements to the patient’s true intention.SignificanceOur study layouts the foundation towards not only a robust and dexterous control strategy for modern neuroprostheses at a near-natural level approaching that of the able hand, but also an intuitive conduit for connecting human minds and machines through the peripheral neural pathways.Clinical trialDExterous Hand Control Through Fascicular Targeting (DEFT). Identifier: NCT02994160.

Summary:. Amputee patients suffer high rates of chronic neuropathic pain, residual limb dysfunction, and disability. Recently, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are 2 techniques that have been advocated for such patients, given their ability to maximize intuitive prosthetic function while also minimizing neuropathic pain, such as residual and phantom limb pain. However, there remains room to further improve outcomes for our residual limb patients and patients suffering from symptomatic end neuromas. “TMRpni” is a nerve management technique that leverages beneficial elements described for both TMR and RPNI. TMRpni involves coaptation of a sensory or mixed sensory/motor nerve to a nearby motor nerve branch (ie, a nerve transfer), as performed in traditional TMR surgeries. Additionally, the typically mismatched nerve coaptation is wrapped with an autologous free muscle graft that is akin to an RPNI. The authors herein describe the “TMRpni” technique and illustrate a case where this technique was employed.

Background: Multi-articulate prostheses are capable of performing dexterous hand movements. However, clinically available control strategies fail to provide users with intuitive, independent and proportional control over multiple degrees of freedom (DOFs) in real-time. New Method: We detail the use of a modified Kalman filter (MKF) to provide intuitive, independent and proportional control over six-DOF prostheses such as the DEKA "LUKE" Arm. Input features include neural firing rates recorded from Utah Slanted Electrode Arrays and mean absolute value of intramuscular electromyographic (EMG) recordings. Ad-hoc modifications include thresholds and non-unity gains on the output of a Kalman filter. Results: We demonstrate that both neural and EMG data can be combined effectively. We also highlight that modifications can be optimized to significantly improve performance relative to an unmodified Kalman filter. Thresholds significantly reduced unintended movement and promoted more independent control of the different DOFs. Gain were significantly greater than one and served to amplify participant effort. Optimal modifications can be determined quickly offline and translate to functional improvements online. Using a portable take-home system, participants performed various activities of daily living. Comparison with Existing Methods: In contrast to pattern recognition, the MKF allows users to continuously modulate their force output, which is critical for fine dexterity. The MKF is also computationally efficient and can be trained in less than five minutes. Conclusions: The MKF can be used to explore the functional and psychological benefits associated with long-term, at-home control of dexterous prosthetic hands., Comment: 10 figures. Accepted in J. Neurosci. Methods (2019)

In recent years, the trigeminal nerve (CN V) has become a popular target for neuromodulation therapies to treat of a variety of diseases due to its access to neuromodulatory centers. Despite promising preclinical and clinical data, the mechanism of action of trigeminal nerve stimulation (TNS) remains in question. In this work, we describe the development and evaluation of a neural interface targeting the mouse trigeminal nerve with the goal of enabling future mechanistic research on TNS. We performed experiments designed to evaluate the ability of a peripheral nerve interface (i.e. cuff electrode) to stimulate the infraorbital branch of the trigeminal nerve. We found that both artificial and naturalistic stimulation of the trigeminal nerve elicited robust cortical responses in the somatosensory cortex that scaled with increases in stimulus amplitude. These results suggest that an infraorbital nerve interface is a suitable candidate for examining the neural mechanisms of TNS in the mouse.

Summary:. Symptomatic neuroma after major extremity amputation is a challenging clinical problem for which there are many described treatment options. Neuroma excision and implantation into the medullary canal of long bones offers durability and insulation, and minimizes chronic pain. Another challenge in amputees is impaired function and an ongoing need for accessible and functional prostheses that are “bidirectional,” in that they provide both fine motor control and sensory feedback. Drawing on clinical experience with neuroma implantation into the medullary canal of long bones, the authors propose a novel neural interface whereby a terminal nerve end is redirected into the medullary canal of a nearby long bone and interfaced with an electrode array. The osseointegrated neural interface aims to exploit electrical signals from peripheral nerves to control advanced prosthetic devices for amputees. The purpose of this article is to present 2 clinical cases of nerve translocation into bone that serve as the clinical foundation of the osseointegrated neural interface as an innovative interface for prosthetic control.

State-of-the-art prosthetic hands nearly match the dexterity of the human hand, and sophisticated approaches have been developed to control them intuitively. However, grasping and dexterously manipulating objects relies heavily on the sense of touch, without which we would struggle to perform even the most basic activities of daily living. Despite the importance of touch, not only in motor control but also in affective communication and embodiment, the restoration of touch through bionic hands is still in its infancy, a shortcoming that severely limits their effectiveness. Here, we focus on approaches to restore the sense of touch through an electrical interface with the peripheral nerve. First, we describe devices that can be chronically implanted in the nerve to electrically activate nerve fibers. Second, we discuss how these interfaces have been used to convey basic somatosensory feedback. Third, we review what is known about how the somatosensory nerve encodes information about grasped objects in intact limbs and discuss how these natural neural codes can be exploited to convey artificial tactile feedback. Finally, we offer a blueprint for how these codes could be implemented in a neuroprosthetic device to deliver rich, natural, and versatile tactile sensations.

We present a wearable interface that allows a user to silently converse with a computing device without any voice or any discernible movements - thereby enabling the user to communicate with devices, AI assistants, applications or other people in a silent, concealed and seamless manner. A user's intention to speak and internal speech is characterized by neuromuscular signals in internal speech articulators that are captured by the AlterEgo system to reconstruct this speech. We use this to facilitate a natural language user interface, where users can silently communicate in natural language and receive aural output (e.g - bone conduction headphones), thereby enabling a discreet, bi-directional interface with a computing device, and providing a seamless form of intelligence augmentation. The paper describes the architecture, design, implementation and operation of the entire system. We demonstrate robustness of the system through user studies and report 92% median word accuracy levels.

Background Regenerative Peripheral Nerve Interfaces (RPNIs) are neurotized muscle grafts intended to produce electromyographic signals suitable for motorized prosthesis control. Two RPNIs producing independent agonist/antagonist signals are required for each control axis; however, it is unknown whether signals from adjacent RPNIs are independent. The purpose of this work was to determine signaling characteristics from two adjacent RPNIs, the first neurotized by a foot dorsi-flexor nerve and the second neurotized by a foot plantar-flexor nerve in a rodent model. Methods Two Control group rats had electrodes implanted onto the soleus (tibial nerve) and extensor digitorum longus (peroneal nerve) muscles in the left hind limb. Two Dual-RPNI group rats had two separate muscles grafted to the left thigh and each implanted with electrodes: the extensor digitorum longus was neurotized with a transected fascicle from the tibial nerve, and the tibialis anterior was implanted with a transected peroneal nerve. Four months post-surgery, rats walked on a treadmill, were videographed, and electromyographic signals were recorded. Amplitude and periodicity of all signals relative to gait period were quantified. To facilitate comparisons across groups, electromyographic signals were expressed as a percent of total stepping cycle activity for each stance and swing gait phase. Independence between peroneal and tibial nerve activations were assessed by statistical comparisons between groups during stance and swing. Results Electromyographic activity for Control and Dual-RPNI rats displayed alternating activation patterns coinciding with stance and swing. Significant signal amplitude differences between the peroneal and tibial nerves were found in both the Control and Dual-RPNI groups. Non-inferiority tests performed on Dual-RPNI group signal confidence intervals showed that activation was equivalent to the Control group in all but the peroneal RPNI construct during stance. The similar electromyographic activity obtained for Control and RPNI suggests the latter constructs activate independently during both stance and swing, and contain minimal crosstalk. Conclusions In-vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Adjacent RPNIs neurotized with agonist/antagonist nerves display activity amplitudes similar to Control during voluntary walking. The distinct and expected activation patterns indicate the RPNI may provide independent signaling in humans, suitable for motorized prosthesis control.

Summary: Symptomatic neuromas and pain caused by nerve transection injuries can adversely impact a patient’s recovery, while also contributing to increased dependence on opioid and other pharmacotherapy. These sources of pain are magnified following amputation surgeries, inhibiting optimal prosthetic wear and function. Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) represent modern advances in addressing amputated peripheral nerves. These techniques offer solutions by essentially providing neuromuscular targets for transected peripheral nerves “to grow into and reinnervate.” Recent described benefits of these techniques include reports on pain reduction or ablation (eg, phantom limb pain, residual limb pain, and/or neuroma pain).1–6 We describe a technical adaptation combining TMR with a “pedicled vascularized RPNI (vRPNI).” The TMR with the vRPNI surgical technique described offers the advantage of having a distal target nerve and a target muscle possessing deinnervated motor end plates which may potentially enhance nerve regeneration and muscle reinnervation, while also decreasing amputated nerve-related pain.

Background Chronic stability and high degrees of selectivity are both essential but somewhat juxtaposed components for creating an implantable bi-directional PNI capable of controlling of a prosthetic limb. While the more invasive implantable electrode arrays provide greater specificity, they are less stable over time due to compliance mismatch with the dynamic soft tissue environment in which the interface is created. New Method This paper takes the surgical approach of transposing nerves into bone to create neural interface within the medullary canal of long bones, an osseointegrated neural interface, to provide greater stability for implantable electrodes. In this context, we describe the surgical model for transfemoral amputation with transposition of the sciatic nerve into the medullary canal in rabbits. We investigate the capacity to create a neural interface within the medullary canal histolomorphologically. In a separate proof of concept experiment, we quantify the chronic physiological capacity of transposed nerves to conduct compound nerve action potentials evoked via an Osseointegrated Neural Interface. Comparison with Existing Method(s) The rabbit serves as an important animal model for both amputation neuroma and osseointegration research, but is underutilized for the exploration neural interfacing in an amputation setting. Results Our findings demonstrate that transposed nerves remain stable over 12 weeks. Creating a neural interface within the medullary canal is possible and does not impede nerve regeneration or physiological capacity. Conclusions This article represents the first evidence that an Osseointegrated Neural Interface can be surgically created, capable of chronic stimulation/recording from amputated nerves required for future prosthetic control.

The essential purpose of neural interfaces is to record and stimulate neural activity. Careful analysis of neural signals allows them to be used to control technologies such as prosthetics and muscle stimulators that restore lost functionality caused by injury. Designing interfaces advanced enough to restore full functionality, however, is a challenge. Presented here is an animal study using the Texas regenerative peripheral nerve interface (TxNI), a novel neural interface device for communicating with peripheral nerves. Small extracellular potentials and concentration of current at the nodes of Ranvier increases the complexity of recording from axons. The TxNI is designed to obtain weak neural signals which are difficult to acquire using other techniques. The TxNI combines a PDMS (polydimethylsiloxane) microchannel scaffold with microwires (used as recording electrodes) embedded within the microchannels. Axonal regeneration is confined to the microchannels and electrodes are long enough to record from the nodes of Ranvier. Although several types of electrodes for peripheral nerve interfaces have been reported, they typically record unwanted signals from surrounding musculature and are subject to crosstalk. To address this, neural regeneration is directed through the TxNI in sealed microfluidic channels. The TxNI was successfully implanted in the rat sciatic nerve in the animal facility at UTPA. The details regarding its fabrication and implantation are described here. The present result is to be used to evaluate the effectiveness of the TxNI for use in advanced prosthetics. In particular, it aims to be used in a noninvasive brain-machine interface for bidirectional prosthetic arms.

Peripheral nerves, due to their small size and complex innervation to organs and complex physiology, pose particularly significant challenges towards interfacing electrodes and electronics to enable neuromodulation. Here, we present a review of the technology for building such interface, including recording and stimulating electrodes and low power electronics, as well as powering. Of particular advantage to building a miniature implanted device is a "bidirectional" system that both senses from the nerves or surrogate organs and stimulates the nerves to affect the organ function. This review and presentation will cover a range of electrodes, electronics, wireless power and data schemes and system integration, and will end with some examples and applications.

We have developed a novel peripheral nerve interface device based on photosensitive polyimides in which nerve fibres regenerate through channels containing electrodes. These Spiral Peripheral Nerve Interfaces (SPNIs) are fabricated by spin coating and curing a layer of polyimide resin onto a silcon handle wafer. Channels 100μm wide are defined in a 100..m thick photosensitive polyimide (PSPI) layer photolithographically. Metal wiring is integrated between the two and encapsulated using a thinner PSPI layer. This design has advantages over others in terms of both recording and stimulation. Initial tests of the device carried out in-vivo show successful regeneration and have demonstrated that we can record signals from regenerated axons. © 2011 Springer-Verlag Berlin Heidelberg.

Technological advances in body armor have proved dramatically effective in reducing torso injuries and deaths among the armed services but have also resulted in a sharp increase in young amputees.1 One in 190 Americans has an amputated limb, and over 185,000 new amputations are performed every year.2 Advances in the field of neuroprosthetics have led to five-fingered designs, achieving as many as 20 degrees of freedom.3,4 The development of shape memory alloy–actuated prosthetic hands allows for more compact, lighter, and easier-to-manufacture prosthetics.5,6 Despite these advances in robotic prosthetic arms, the tissue–prosthetic interface remains a persistent problem.7 High charge density (C/m2) at the interface leads to chronic macrophage and fibroblast response with biofouling, leading to signal degradation over time.8 Chronic, closed loop control of a prosthesis requires both precision and sensitivity when recording or stimulating action potentials at the tissue–electrode interface. Interface charge density can be reduced by increasing electrode charge capacity and decreasing electrical impedance.9 High charge capacity, which is a measurement of charge transfer efficiency, facilitates more efficient recording and stimulation of action potentials at a lower charge density at the biotic–abiotic interface.10 A variety of electrically conductive polymers exist with high charge capacity and low electrical impedance. The use of one such polymer, poly-(3,4-ethylenedioxythiophene), PEDOT, has been explored by several groups for coating electrodes that are implanted in the central nervous system for long periods of time.11–13 They have shown good short-term improvement in recording fidelity for up to 6 weeks following implantation.11–13 Oxygen and sulfur substitutions along the carbon backbone of the PEDOT molecule produce an insulated resonance pathway for ionic conduction along the molecular backbone. This ionic conduction helps bridge the differences between electrical conduction of the electrode and the ionic conduction of nerve impulses. It is also responsible for the high charge capacity of PEDOT.14 There are a number of other polymers with similar properties that may be helpful in a peripheral nerve interface, including poly(pyrrole) and poly(5,6-dimethoxyindole-2-carboxylic acid).15,16 Unlike PEDOT, these polymers lose their conductive properties after serial and chronic stimulation. In addition, there are novel polymers that are melanin derived that also may be helpful in peripheral nerve interfaces, but these remain expensive and difficult to polymerize in significant quantities.17 Carbon nanotubes represent another area of intense interest, but their biocompatibility remains questionable.18,19 The purpose of this study was to determine whether electrodes polymerized with the electrically conductive polymer PEDOT have an improved ability to both record and stimulate neural signals in the peripheral nervous system. Experimental groups of plain stainless-steel electrodes and PEDOT-polymerized electrodes were compared for electrical/ionic conduction characteristics and for their performance during in situ nerve conduction studies. Bench tests included impedance spectroscopy and cyclic voltammetry to measure electrode impedance and charge capacity. These measurements allowed comparisons of electrode fidelity and signal precision. Acute in situ nerve conduction studies were then performed on normal rats. Once again, the independent experimental variable was whether or not the electrode was polymerized with PEDOT.14 Separate nerve conduction studies compared electrode type for sensitivity as recording electrodes and as stimulating electrodes.

The task of discriminating the neural pathways responsible for the activity recorded using a multi-contact nerve cuff electrode has recently been approached as an inverse problem of source localization, similar to EEG source localization. A major drawback of this method is that it requires a model of the nerve, and that the localization performance is highly dependent on the accuracy of this model. Using recordings from a 56-contact "matrix" cuff electrode placed on a rat sciatic nerve, we investigated a method that eliminates the need for a model, and uses instead an "experimental" leadfield constructed from a training set of experimental recordings. The resulting pathway-identification task is solved using an inverse problem framework. The experimental leadfield approach was able to identify the correct branch in cases in which a single fascicle was active with a success rate of 94.2%, but was not able to reliably identify combinations of fascicles. Nevertheless, the proposed methodology provides a framework for the study of multi-pathway discrimination, within which methods to improve performance can be investigated. Specifically, the influence of nerve anatomy and electrode design should be examined, and regularization approaches better suited to this novel inverse problem should be sought.

Limb loss and spinal cord injury are two debilitating conditions that continue to grow in prevalence. Prosthetic limbs and limb reanimation present two ways of providing affected individuals with means to interact in the world. These techniques are both dependent on a robust interface with the peripheral nerve. Current methods for interfacing with the peripheral nerve tend to suffer from low specificity, high latency and insufficient robustness for a chronic implant. An optical peripheral nerve interface may solve some of these problems by decreasing invasiveness and providing single axon specificity. In order to implement such an interface three elements are required: (1) a transducer capable of translating light into a neural stimulus or translating neural activity into changes in fluorescence, (2) a means for delivering said transducer and (3) a microscope for providing the stimulus light and detecting the fluorescence change. There are continued improvements in both genetically encoded calcium and voltage indicators as well as new optogenetic actuators for stimulation. Similarly, improvements in specificity of viral vectors continue to improve expression in the axons of the peripheral nerve. Our work has recently shown that it is possible to virally transduce axons of the peripheral nerve for recording from small fibers. The improvements of these components make an optical peripheral nerve interface a rapidly approaching alternative to current methods.

Successful treatment of the painful neuroma is a particular challenge to the nerve surgeon. Historically, symptomatic neuromas have primarily been treated with excision and implantation techniques, which are inherently passive and do not address the terminal end of the nerve. Over the past decade, the surgical management of neuromas has undergone a paradigm shift synchronous with the development of contemporary techniques aiming to satisfy the nerve end. In this article, we describe the important features of surgical treatment, including the approach to diagnosis with consideration of neuroma type and the decision of partial versus complete neuroma excision. A comprehensive list of the available surgical techniques for management following neuroma excision is presented, the choice of which is often predicated upon the availability of the terminal nerve end for reconstruction. Techniques for neuroma reconstruction in the presence of an intact terminal nerve end include hollow tube reconstruction and auto- or allograft nerve reconstruction. Techniques for neuroma management in the absence of an intact or identifiable terminal nerve end include submuscular or interosseous implantation, centro-central neurorrhaphy, relocation nerve grafting, nerve cap placement, use of regenerative peripheral nerve interface, "end-to-side" neurorrhaphy, and targeted muscle reinnervation. These techniques can be further categorized into passive/ablative and active/reconstructive modalities. The nerve surgeon must be aware of available treatment options and should carefully choose the most appropriate intervention for each patient. Comparative studies are lacking and will be necessary in the future to determine the relative effectiveness of each technique.

Objective Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. Approach Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. Main results Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. Significance In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.

Background This study compared epimysial patch electrodes with intramuscular hook electrodes using monopolar and bipolar recording configurations. The purpose was to determine which strategy transduced muscle signals with better fidelity for control of myoelectric prostheses. Methods One of the two electrode styles, patch (n = 4) or hook (n = 6) was applied to the left extensor digitorum longus muscle in rats. Electrodes were evaluated at the time of placement and at monthly intervals for 4 months. Evaluations consisted of evoked electromyography signals from stimulation pulses applied to the peroneal and tibial nerves in both monopolar and bipolar recording configurations. Results Compared with hook electrodes, patch electrodes recorded larger signals of interest and minimized muscle tissue injury. A bipolar electrode configuration significantly reduced signal noise when compared with a monopolar configuration. Conclusion Epimysial patch electrodes outperform intramuscular hook electrodes during chronic skeletal muscle implantation.

Each year, approximately 185,000 Americans suffer the devastating loss of a limb. The effects of upper limb amputations are profound because a person's hands are tools for everyday functioning, expressive communication, and other uniquely human attributes. Despite the advancements in prosthetic technology, current upper limb prostheses are still limited in terms of complex motor control and sensory feedback. Sensory feedback is critical to restoring full functionality to amputated patients because it would relieve the cognitive burden of relying solely on visual input to monitor motor commands and provide tremendous psychological benefits. This article reviews the latest innovations in sensory feedback and argues in favor of peripheral nerve interfaces. First, the authors examine the structure of the peripheral nerve and its importance in the development of a sensory interface. Second, the authors discuss advancements in targeted muscle reinnervation and direct neural stimulation by means of intraneural electrodes. The authors then explore the future of prosthetic sensory feedback using innovative technologies for neural signaling, specifically, the sensory regenerative peripheral nerve interface and optogenetics. These breakthroughs pave the way for the development of a prosthetic limb with the ability to feel.