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PurPose: Regenerative Peripheral Nerve Interfaces (RPNI) are neurotized autologous free muscle grafts equipped with electrodes to record myoelectric signals for prosthetic control. RPNI devices implanted into rats have been shown, using... more
PurPose: Regenerative Peripheral Nerve Interfaces (RPNI) are neurotized autologous free muscle grafts equipped with electrodes to record myoelectric signals for prosthetic control. RPNI devices implanted into rats have been shown, using evoked responses, to be stable and viable for up to 2 years. In vivo characterization of RPNI signaling is critical for assessing their utility as a control modality for prosthetic devices. This work quantifies RPNI signal activation and relates it to gait; its ultimate purpose is to define signaling relationships between RPNI and native muscle during volitional control.
ABSTRACT Regenerative peripheral nerve interfaces (RPNIs) are implantable devices for amputee communication between peripheral nerves and microprocessor controlled robotic prostheses. Our RPNIs consist of transferred muscles reinnervated... more
ABSTRACT Regenerative peripheral nerve interfaces (RPNIs) are implantable devices for amputee communication between peripheral nerves and microprocessor controlled robotic prostheses. Our RPNIs consist of transferred muscles reinnervated by the peripheral nerves remaining in the limb post amputation. RPNI construction includes a light muscle wrap of decellularized small-intestine submucosa (SIS). We studied RPNI revascularization and regeneration when SIS had an electrically conductive coating of poly 3,4 ethylene dioxytheophene (PEDOT). Rats underwent free-muscle transfer (FMT). The peroneal nerve was divided and the proximal end was implanted in the FMT. Experimental groups received either: a) no SIS (NONE), b) SIS (SIS) wrap, or c) wrap of SIS polymerized with PEDOT, (SIS+PEDOT). One week later, rats were perfused with lead oxide, vascular areas were quantified and histology was performed. SIS+PEDOT group muscles contained less revascularization under the wrap than the SIS group, (p=.05). Histology showed that at 7 days, muscle fibers in the SIS+PEDOT group were not degenerating and regenerating similarly to those muscle fibers in the NONE and SIS groups. Images of SIS and SIS+PEDOT indicate the PEDOT filled the pores of the SIS. This reduced porosity may prohibit revascularization through the SIS+PEDOT. Data indicate that revascularization in the NONE and SIS groups are similar to control muscle while vascularity in the SIS+PEDOT group is impaired by SIS+PEDOT.
In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to... more
In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to both on-chip and real-time applications. CAR is commonly used in EEG, where it is necessary to identify small signal sources in very noisy recordings. To study the efficacy of common average referencing, we compared CAR to both referencing with a stainless steel bone-screw and a single microelectrode site. Data consisted of in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior studies, as well as previously unpublished data. By combining the data from multiple studies, we generated and analyzed one of the more comprehensive chronic neural recording datasets to date. Reference types were compared in terms of noise level, signal-to-noise ratio, and number of neurons recorded across days. Common average referencing was found to drastically outperform standard types of electrical referencing, reducing noise by >30%. As a result of the reduced noise floor, arrays referenced to a CAR yielded almost 60% more discernible neural units than traditional methods of electrical referencing. CAR should impart similar benefits to other microelectrode recording technologies—for example, chemical sensing—where similar differential recording concepts apply. In addition, we provide a mathematical justification for CAR using Gauss-Markov theorem and therefore help place the application of CAR into a theoretical context.
The BRAIN Initiative® arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and... more
The BRAIN Initiative® arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought." The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system. As the Initiative enters its fifth year, NIH has supported over 500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities. We describe scientific advances produced by individual labs, multi-investigator teams, and entire consortia that, over the coming decades, will produce more comprehensive and dynamic maps of the brain, deepen ...
ABSTRACT Objective: Nonvascularized partial skeletal muscle grafts are notorious for their limited force-generating capacity and tendency to degenerate in the absence of reinnervation. Accompanied by peripheral nerve implantation,... more
ABSTRACT Objective: Nonvascularized partial skeletal muscle grafts are notorious for their limited force-generating capacity and tendency to degenerate in the absence of reinnervation. Accompanied by peripheral nerve implantation, however, partial muscle grafts can survive and transmit detectable electromyographic (EMG) signals capable of prosthetic control. Our study investigated partial muscle graft survival in the construction of regenerative peripheral nerve interfaces (RPNIs) and further characterized their electrophysiological properties across various muscle donor sites. Methods: Twenty F344 rats were assigned to 1 of 5 groups based on muscle graft type used for RPNI construction: 1) control-whole extensor digitorum longus; 2) partial biceps femoris; 3) partial rectus femoris; 4) partial lateral gastrocnemius; and 5) partial vastus medialis. Each graft (approximately 140-mg at initial harvest) was fixed to the femur, wrapped in small intestinal submucosa for tissue isolation, and implanted with the transected common peroneal nerve. After 4 months of recovery, in situ EMG and force testing were performed [Figure 1]. Results: All control RPNIs (n=4) transmitted detectable EMG signals, compared to 75% of partial muscle RPNIs (n=12 of 16). Significant differences between control and partial muscle RPNIs included average mass [118-mg (SD 42) vs. 66-mg (SD 25)], EMG peak-to-peak amplitude [6.7-mV (SD 2.3) vs. 1.16-mV (SD 1.5)], and maximum tetanic force [500-mN (SD 615) vs. 137-mN (SD 152)] [Figure 2]. Amongst partial muscle groups, donor muscle was not a significant predictor of EMG amplitude after adjusting for final RPNI mass and length at 4 months. Conclusions: We report that partial muscle graft RPNIs transmit detectable EMG signals with a 75% success rate at 4 months. This proof of concept underscores the potential to develop and refine partial muscle graft-based interfaces to harness peripheral motor nerve signals for prosthetic control. While signal size remains favorable (i.e. 10-100 times larger than signals recorded directly from peripheral nerves), further studies are warranted for optimization of partial muscle graft regeneration and methods of signal acquisition. Acknowledgements: This work was supported by DARPA (N66001-11-C-4190), the Plastic Surgery Foundation, and the Frederick A. Coller Surgical Society.
ABSTRACT
The availability of sophisticated neural probes is a key prerequisite in the development of future brain-machine interfaces (BMIs). In this study, the authors developed and validated a neural probe design capable of simultaneous drug... more
The availability of sophisticated neural probes is a key prerequisite in the development of future brain-machine interfaces (BMIs). In this study, the authors developed and validated a neural probe design capable of simultaneous drug delivery and electrophysiology recordings in vivo. Focal drug delivery promises to extend dramatically the recording lives of neural probes, a limiting factor to clinical adoption of BMI technology. To form the multifunctional neural probe, the authors affixed a 16-channel microfabricated silicon electrode array to a fused silica catheter. Three experiments were conducted in rats to characterize the performance of the device. Experiment 1 examined cellular damage from probe insertion and the drug distribution in tissue. Experiment 2 measured the effects of saline infusions delivered through the probe on concurrent electrophysiological measurements. Experiment 3 demonstrated that a physiologically relevant amount of drug can be delivered in a controlled fashion. For these experiments, Hoechst and propidium iodide stains were used to assess insertion trauma and the tissue distribution of the infusate. Artificial CSF (aCSF) and tetrodotoxin (TTX) were injected to determine the efficacy of drug delivery. The newly developed multifunctional neural probes were successfully inserted into rat cortex and were able to deliver fluids and drugs that resulted in the expected electrophysiological and histological responses. The damage from insertion of the device into brain tissue was substantially less than the volume of drug dispersion in tissue. Electrophysiological activity, including both individual spikes as well as local field potentials, was successfully recorded with this device during real-time drug delivery. No significant changes were seen in response to delivery of aCSF as a control experiment, whereas delivery of TTX produced the expected result of suppressing all spiking activity in the vicinity of the catheter outlet. Multifunctional neural probes such as the ones developed and validated within this study have great potential to help further understand the design space and criteria for the next generation of neural probe technology. By incorporating integrated drug delivery functionality into the probes, new treatment options for neurological disorders and regenerative neural interfaces using localized and feedback-controlled delivery of drugs can be realized in the near future.
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... more
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 ele...
Each year, approximately 185,000 Americans suffer the devastating loss of a limb. The effects of upper limb amputations are profound because a... more
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.
ABSTRACT In the near future, upper limb prostheses may interface with peripheral nerves of amputees to help restore vital somatosensory feedback. Achieving that goal requires the transformation of forces artificially sensed in our... more
ABSTRACT In the near future, upper limb prostheses may interface with peripheral nerves of amputees to help restore vital somatosensory feedback. Achieving that goal requires the transformation of forces artificially sensed in our environment into the depolarization of afferents, by delivering levels of charge adequate for signaling tactile sensory cues yet avoiding tissue damage. The objective of the work herein was to build and test a tactile afferent modulation platform engineered to transform force data input, from an artificial sensor under ramp-and-hold stimuli, into the output of discrete charge-balanced pulses to the rat's acute sural nerve thereby eliciting compound sensory neural action potentials (CSNAPs). In vivo experiments, to stimulate both tactile end organs mechanically and sural nerves electrically, helped fit the model's empirical parameters. Input-output relationships were validated by comparing CSNAPs elicited by the tactile afferent modulation platform with those of natural end organs. The results replicated the natural response where increased force magnitude increased both CSNAP firing rates and waveform amplitudes. Next steps will involve the integration of the engineered platform with a regenerative peripheral nerve interface for the evaluation of its long-term reliability.
High-fidelity volitional control of bioengineered prosthetic limbs with multiple degrees of freedom requires the implantation of multiple recording interfaces to detect independent control signals. However, interface utilization is... more
High-fidelity volitional control of bioengineered prosthetic limbs with multiple degrees of freedom requires the implantation of multiple recording interfaces to detect independent control signals. However, interface utilization is complicated by interfering electrophysiological signals originating from surrounding muscles and nerves, leading to equivocal signal detection. We developed and validated a surgical model to characterize signal propagation through various biomaterials to identify insulating substrates for use in implantable interfaces. The identification of these insulating materials will facilitate the acquisition of noncontaminated prosthetic control signals, thus improving manipulation of advanced prosthetic limbs. Using a rat hindlimb model, 4 groups (n = 8/group) were tested. A medial gastrocnemius muscle flap was elevated, leaving the neurovascular pedicle intact. The flap was rotated into a chamber and secured to a silicone base. A stainless steel electrode was aff...
ABSTRACT The Regenerative Peripheral Nerve Interface (RPNI) has the capacity to provide fine motor control and sensory feedback to advanced robotic limbs by interfacing directly with the residual extremity of an amputee. RPNI electrodes... more
ABSTRACT The Regenerative Peripheral Nerve Interface (RPNI) has the capacity to provide fine motor control and sensory feedback to advanced robotic limbs by interfacing directly with the residual extremity of an amputee. RPNI electrodes must provide high fidelity stimulation and recording capability without compromising biological integrity at the electrode-tissue interface. To identify an optimal electrode for utilization with the RPNI, multiple electrode types were characterized in vitro and in vivo. Electrochemical impedance spectroscopy, cyclic voltammetry, and in vivo electromyography (EMG) were performed. All electrodes demonstrated favorable performance. The platinum (Pt) needle and pacemaker lead exhibited lower impedance and higher charge storage capacity values during in vitro testing. Electrophysiological testing revealed that at threshold stimulation, the Pt needle and stainless steel (SS) pad electrodes recorded a larger signal of interest relative to the other experimental electrodes, while the SS pad, flexible microwire, and pacemaker lead demonstrated a larger relative signal at maximal stimulation. Several electrodes which exhibited favorable performance were identified for use in the RPNI.
ABSTRACT Regenerative peripheral nerve interfaces (RPNIs) transfer motor and sensory signals between amputee and prosthesis. Von Frey (VF) monofilaments are used clinically to evaluate sensory feedback but have not been validated at... more
ABSTRACT Regenerative peripheral nerve interfaces (RPNIs) transfer motor and sensory signals between amputee and prosthesis. Von Frey (VF) monofilaments are used clinically to evaluate sensory feedback but have not been validated at locations used in our rodent studies. Our purposes were to determine VF sensory test reliability at the ankle and thigh, and to evaluate sensory function of Mixed Nerve (MN) and Sensory Nerve (SN) RPNIs. For reliability testing, VF monofilaments were applied to Normal rats at the ankle and thigh in an up-down pattern. Paw Withdraw Thresholds were determined by alternately exceeding and reducing filament pressure. VF tests were then administered to experimental MN-RPNIs or SN-RPNIs. Reliability results at the ankle showed sensation did not vary over six weeks. At the thigh, reliability was similar during week 0 and 1, but with further testing sensation increased. Comparison between location found at weeks 0 and 1, the ankle was significantly more sensitive than the thigh (p
High-fidelity signal acquisition is critical for the fundamental control of a neuroprosthesis. Our group has developed a bio-artificial interface consisting of a muscle graft neurotized by a severed nerve in a rat hind limb model. This... more
High-fidelity signal acquisition is critical for the fundamental control of a neuroprosthesis. Our group has developed a bio-artificial interface consisting of a muscle graft neurotized by a severed nerve in a rat hind limb model. This regenerative peripheral nerve interface (RPNI) permits nerve signal transmission, amplification, and detection via in situ electromyography (EMG). Our study examined the magnitude of signal interference from simultaneously contracting muscles adjacent to our muscle of interest. In eighteen F344 rats, the extensor digitorum longus (EDL) muscle was used to fabricate simulated RPNI constructs of various sizes in which the neurovascular pedicle was preserved, obviating the need for reinnervation or revascularization. After 3 weeks of recovery, in situ EMG testing was performed using electrical stimulation of the common peroneal nerve. A recording needle was placed in the EDL muscle with a reference/ground electrode in the contralateral toe webspace, comprising a monopolar recording configuration. The superficial peroneal nerve was transected to further isolate stimulation of the anterior compartment. Recordings from the EDL were performed before and after excision of the tibialis anterior (TA) and extensor hallucis longus (EHL) muscles. After TA/EHL excision, EDL compound muscle action potential (CMAP) peak-to-peak amplitudes were significantly lower by an average of 7.4±5.6(SD) mV, or 32±18%, (paired t(17)=-5.7, p<;0.0001). A significant positive linear correlation was seen between CMAP amplitude and EDL mass both before TA/EHL excision (r=0.68, n=18, p<;0.01) and after TA/EHL excision (r=0.79, n=18, p<;0.0001). EDL mass did not correlate with differences in CMAP amplitude or area caused by TA/EHL excision. Monopolar needle EMG recordings from the EDL muscle are significantly, but predictively, contaminated by concomitant muscular contractions in the anterior compartment of the rat hind limb. Further investigation of strategies to reduce this signal interference, including electrode choice or configuration, use of bioelectrical insulators, and filtering methods, is warranted to promote high-fidelity signal acquisition for prosthetic control.
Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which... more
Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which give patients high-fidelity control of these artificial limbs are limited. We have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which consists of a unit of free muscle that has been neurotized by a transected peripheral nerve. In conjunction with a biocompatible electrode on the muscle surface, the RPNI facilitates signal transduction from a residual peripheral nerve to a neuroprosthetic limb. The purpose of this study was to explore signal quality and reliability in an RPNI following an extended period of implantation. Following a 14-month maturation period, electromyographic signal generation was evaluated via electrical stimulation of the innervating nerve. The long-term RPNI was viable and healthy, as demonstrated by evoked compound muscle action potentials as well as histological tissue analysis. Signals exceeding 4 mV were successfully acquired and amplitudes were consistent across multiple repetitions of applied stimuli. There were no evident signs of muscle denervation, significant scar tissue, or muscle necrosis. This study provides further evidence that after a maturation period exceeding 1 year, reliable and consistent signals can still be acquired from an RPNI.
The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual... more
The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer. In a rat model, the extensor digitorum longus muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided peroneal nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was implanted on the muscle transfer and secured with an encircling acellular extracellular matrix. The contralateral muscle served as the control. The free muscle transfers we...
To present the recent advances in the treatment of facial paralysis, emphasizing the emerging technologies. This review will summarize the current state of the art in the management of facial paralysis and discuss the advances in nerve... more
To present the recent advances in the treatment of facial paralysis, emphasizing the emerging technologies. This review will summarize the current state of the art in the management of facial paralysis and discuss the advances in nerve regeneration, facial reanimation, and use of novel biomaterials. This review includes surgical innovations in reinnervation and reanimation as well as progress with bioelectrical interfaces. The last decade has witnessed major advances in the understanding of nerve injury and approaches for management. Key innovations include strategies to accelerate nerve regeneration, provide tissue-engineered constructs that may replace nonfunctional nerves, approaches to influence axonal guidance, limiting of donor-site morbidity, and optimization of functional outcomes. Approaches to muscle transfer continue to evolve, and new technologies allow for electrical nerve stimulation and use of artificial tissues. The fields of biomedical engineering and facial reanima...
ABSTRACT Background: Limited evidence exists to guide surgical decision-making following traumatic major upper extremity amputations, with few published reports focusing on clinical indications for attempting replantation.1-4 This study... more
ABSTRACT Background: Limited evidence exists to guide surgical decision-making following traumatic major upper extremity amputations, with few published reports focusing on clinical indications for attempting replantation.1-4 This study characterizes major upper extremity amputation in a civilian population, ascertains clinical factors associated with the decision to attempt replantation, and analyzes associations between reconstructive efforts and favorable clinical outcomes. Methods: A retrospective cohort study was conducted on patients treated at the University of Michigan Level One trauma center between June 2000 and August 2011. Patients who experienced traumatic upper extremity amputation at or proximal to the radio-carpal joint were included in the study. The subset of patients who subsequently underwent replantation was identified. Medical records were reviewed to collect patient demographics, injury characteristics, operative details, and clinical outcomes. Bivariate analysis was performed to identify factors associated with attempted replantation, as well as resultant clinical outcomes. Results: Sixty two patients were treated for traumatic upper extremity amputation and 20 patients underwent attempted replantation. Mean follow up was 2.8 years. Injury factors associated with attempted replantation included a sharp/penetrating injury (p=0.004), distal level of amputation (p=0.017), injury severity score (ISS) of less than 16 at presentation (p=0.020), absence of avulsion (p=0.002), absence of significant contamination (p=<0.001), and lack of multilevel involvement (p=0.007). Upper extremity replantation exhibited a complete survival rate of 70%. An ISS ≥ 16 was associated with failure of the replanted limb (p=0.004). Patients who underwent replantation demonstrated an increased overall rate of secondary surgical revisions (75%) compared with those who were not replanted (26.2%, p=<0.001), including a significantly increased requirement for post-operative split-thickness skin grafts (30% vs. 2.4%, p=0.003) and complex tissue rearrangements (20% vs. 0%, p=0.009). Replanted patients also demonstrated an increased overall rate of postoperative complications (85.0%) compared to patients who received revision amputations (52.4%, p=0.023), and specifically exhibited an increased rate of wound breakdown/chronic wound formation (40% vs. 14.3%, p=0.048). Replantation was also associated with a greater length of hospital stay (15 vs. 9 days, p=0.024). Conclusion: Several injury characteristics are associated with the decision to attempt replantation of the upper extremity. When performed, a high global injury severity (ISS≥16) is associated with replantation failure. Furthermore, patients who undergo attempted replantation demonstrate higher resource utilization, a finding which spurs further cost-analysis and outcomes investigation.
ABSTRACT PURPOSE: Regenerative Peripheral Nerve Interfaces (RPNIs) transfer signals between an amputee's residual limb and motorized prostheses. RPNIs are surgically transferred autologous muscle neurotized by residual nerve... more
ABSTRACT PURPOSE: Regenerative Peripheral Nerve Interfaces (RPNIs) transfer signals between an amputee's residual limb and motorized prostheses. RPNIs are surgically transferred autologous muscle neurotized by residual nerve fascicles. Implanted electrodes transduce electromyographic signals from the RPNIs. RPNI signals have been shown to control brief prosthetic movements; but, RPNI use during prolonged, activity has not been demonstrated. Our purpose was to measure both RPNI maximal signaling capacity and signaling during continuous, repetitive, submaximal use. METHODS: Rats were assigned to either RPNI (n=4) or Control (n=7) groups. For the RPNI group, the extensor digitorum longus (EDL) muscle was transferred to the thigh and neurotized by the transected peroneal nerve. Bipolar electrodes were secured to the EDL muscles in each group. Five months post-surgery, maximal compound muscle action potential (CMAP) and maximal contractile force were measured following peroneal nerve stimulation. A 20 minute intermittent activation protocol that fatigues normal muscle was administered. This submaximal force protocol totaled 720 repeats of muscle excitation, contraction, and relaxation (Fig 1). Short excitations were evoked by 300 milliseconds of stimulation each second repeated for 360 contractions. This was followed by long excitations evoked by 600 milliseconds of stimulation per second for another 360 contractions. After five minutes of rest, maximal excitation was again measured. RESULTS: A high correlation was verified between maximal CMAP and maximal contractile force, r=0.81, p < 0.01 indicating RPNI signaling. RPNI group CMAP was 32% and maximal force was 23% of Control group amplitudes. The RPNI group averaged 26% of maximal force during shorter contractions and 10% during longer contractions (Fig 2). The Control group maintained 28% and 23% of maximal force during short and long contractions. Following the repetitive activations and a five minute rest, RPNIs recovered maximal contractile signaling on average equaling 72% of their individual initial maximal force while Controls recovered 87% of their initial max force production. Conclusion: Though signals produced by the RPNIs were not as large as Controls, signaling from the RPNIs resisted fatigue during repetitive activation similarly to Control muscle. RPNIs also showed recovery of maximal signaling within five minutes of repeated contractions. All RPNI signals were in the millivolt or milliNewton range with sufficient information to control prostheses. Acknowledgements: Defense Advanced Research Projects Agency (DARPA) MTO Contract No. N66001-11-C-4190.
Advancements in modern robotic technology have led to the development of highly sophisticated upper extremity prosthetic limbs. High-fidelity volitional control of these devices is dependent on the critical interface between the patient... more
Advancements in modern robotic technology have led to the development of highly sophisticated upper extremity prosthetic limbs. High-fidelity volitional control of these devices is dependent on the critical interface between the patient and the mechanical prosthesis. Recent innovations in prosthetic interfaces have focused on several control strategies. Targeted muscle reinnervation is currently the most immediately applicable prosthetic control strategy and is particularly indicated in proximal upper extremity amputations. Investigation into various brain interfaces has allowed acquisition of neuroelectric signals directly or indirectly from the central nervous system for prosthetic control. Peripheral nerve interfaces permit signal transduction from both motor and sensory nerves with a higher degree of selectivity. This article reviews the current developments in each of these interface systems and discusses the potential of these approaches to facilitate motor control and sensory feedback in upper extremity neuroprosthetic devices.
METHODS: F344 rats (n= 29) were randomized into 3 groups. During Sham surgeries, the right soleus muscle was exposed (Sham, n= 11). For RPNI not neurotized (RPNI-NN, n= 9) and neurotized (RPNI+ N, n= 9) devices, the left peroneal nerve... more
METHODS: F344 rats (n= 29) were randomized into 3 groups. During Sham surgeries, the right soleus muscle was exposed (Sham, n= 11). For RPNI not neurotized (RPNI-NN, n= 9) and neurotized (RPNI+ N, n= 9) devices, the left peroneal nerve was divided and the right soleus muscle was transferred to the left thigh simulated residual limb area. For the RPNI+ N device, the divided left nerve was used to neurotize the soleus. SIS was wrapped around all devices. Electrodes were implanted at evaluation. Measurements included nerve ...
Neural prostheses are electrode arrays implanted in the nervous system that record or stimulate electrical activity in neurons. Rapid growth in the use of neural prostheses in research and clinical applications has occurred in recent... more
Neural prostheses are electrode arrays implanted in the nervous system that record or stimulate electrical activity in neurons. Rapid growth in the use of neural prostheses in research and clinical applications has occurred in recent years, but instability and poor patency in the tissue-electrode interface undermines the longevity and performance of these devices. The application of tissue engineering strategies to the device interface is a promising approach to improve connectivity and communication between implanted electrodes and local neurons, and several research groups have developed new and innovative modifications to neural prostheses with the goal of seamless device-tissue integration. These approaches can be broadly categorized based on the strategy used to maintain and regenerate neurons at the device interface: (1) redesign of the prosthesis architecture to include finer-scale geometries and/or provide topographical cues to guide regenerating neural outgrowth, (2) incorp...
METHODS: In fifteen rats, the epimysium of the left extensor digitorum longus (EDL) muscle was implanted with either electrode alone (electrode, n= 5), silk suture alone (suture, n= 5), or electrode with silk suture (electrode+ suture, n=... more
METHODS: In fifteen rats, the epimysium of the left extensor digitorum longus (EDL) muscle was implanted with either electrode alone (electrode, n= 5), silk suture alone (suture, n= 5), or electrode with silk suture (electrode+ suture, n= 5). Each group including the right EDL muscle (control, n= 15) was encircled with a single layer of decellular small intestinal submucosa (SIS). After 30 days, needle electromyography (EMG) and nerve conduction studies were performed, and muscles were harvested for histology.
ABSTRACT Introduction: We are developing a regenerative peripheral nerve interface (RPNI) to achieve high fidelity, intuitive prosthetic control.1,2 Multiaxial control of individual actuators within advanced neuroprostheses requires... more
ABSTRACT Introduction: We are developing a regenerative peripheral nerve interface (RPNI) to achieve high fidelity, intuitive prosthetic control.1,2 Multiaxial control of individual actuators within advanced neuroprostheses requires implantation of multiple adjacent yet electrically independent RPNIs, necessitating effective signal isolation.3-5 This study investigates the acute and long-term efficacy of silicone insulators to reduce extraneous signal in an RPNI. Methods: Using a rat hindlimb model, acute and long term evaluations were performed: 1) acute evaluations were performed using non-transferred extensor digitorum longus (EDL) muscle with an intact neurovascular supply (n=8); and 2) chronic RPNI implantations (n=3) were performed using EDL free-muscle transfer to the ipsilateral thigh. RPNI neurotization was performed by transecting and implanting the common peroneal nerve into the transferred muscle. A recording electrode with an overlying 7x5x1mm silicone layer (experimental), and an uninsulated recording electrode (control), were affixed to the EDL muscle surface. The entire construct was then encircled with small intestinal submucosa. The peroneal nerve was stimulated to activate the muscle of interest, whereas the tibial nerve was stimulated to emit extraneous signal from the posterior compartment. Electromyography was performed immediately for acute evaluations, and 6 weeks postoperatively for chronic implantations. Data were analyzed using paired samples T-test. Results: Acute evaluation: At stimulation threshold, the experimental electrode recorded 47.5% extraneous signal whereas the control electrode recorded 55.9%, revealing an 8.4% improvement in signal isolation by utilizing the silicone insulator (p=0.030). At maximum stimulation, the experimental electrode recorded 53.2% extraneous signal versus the 62.7% recorded from the control electrode, demonstrating an improvement of 9.5% (p=0.001). Chronic RPNI: At both threshold and maximum stimulation of the peroneal nerve, the experimental electrode recorded signals which were similar to the control electrode for latency and noise, but demonstrated marginally reduced compound muscle action potential (CMAP) amplitude and area. Tibial nerve stimulation revealed that the isolation of extraneously derived EMG signals was improved in the experimental electrode, reducing 4%-11% of the extraneous signal compared to control. Conclusion: While signal acquisition is marginally impaired by silicone insulation, electrophysiological characteristics follow a pattern of early regeneration similar to uninsulated muscle. Although additional strategies will likely be required to optimize signal separation, utilization of a silicone insulator results in improved signal isolation and is a feasible option for incorporation into an RPNI.
ABSTRACT Objective: Intuitive control of neuroprosthetic limbs requires a stable, high-fidelity interface between the patient and the device. The Regenerative Peripheral Nerve Interface (RPNI) consists of a unit of freely grafted muscle... more
ABSTRACT Objective: Intuitive control of neuroprosthetic limbs requires a stable, high-fidelity interface between the patient and the device. The Regenerative Peripheral Nerve Interface (RPNI) consists of a unit of freely grafted muscle that is neurotized by a transected peripheral nerve. In conjunction with an electrode on the surface of the grafted muscle, the RPNI facilitates signal transduction from the residual peripheral nerve to an artificial limb. Electrodes can be coated with conductive polymer to enhance conductivity. This study examines the augmentation of signal strength and fidelity from the RPNI when conductive polymer is applied to implanted stainless steel electrodes. Methods: In a rat model, the left extensor digitorum longus (EDL) muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided ipsilateral common peroneal nerve (Figure 1). The RPNI was interfaced with either a stainless steel pad electrode (SS, n=8) or a pad electrode coated with poly(3,4-ethylenedioxy-thiophene) conductive polymer (PEDOT, n=8). Acellular extracellular matrix was used to secure the electrode on the surface of the muscle and separate the RPNI from surrounding tissues. The contralateral EDL muscle of each rat served as control. Monthly electrophysiological testing was performed using percutaneous nerve stimulation while recording from the implanted electrode. Results: The free EDL muscle transfer remained healthy with successful revascularization and reinnervation as evidenced by robust transduction of compound muscle action potentials (CMAPs) through the RPNI. Histologic examination confirms axonal sprouting, elongation, and synaptogenesis within RPNIs. The PEDOT coating resulted in significant increases in elicited signal amplitude at all time points compared to uncoated SS electrodes. This signal augmentation with PEDOT-coated electrodes was observed throughout the course of the study (Figure 2). At 5 months, the PEDOT group displayed a 78% increase in mean maximum CMAP amplitude (PEDOT=7.940.82 mV, SS=4.461.36 mV). Conclusion: Implanted electrodes with and without conductive polymer can be used with the RPNI to bridge the critical signaling gap between a living peripheral nerve and a prosthetic device. All RPNIs in this study demonstrated reinnervation and transduction of bioelectric signals which can be used to control a prosthetic device. Conductive polymer increases RPNI signal amplitude and displays reliability over 5 months. Continued serial evaluations are underway to examine the long-term effects of tissue integration and recording performance of the RPNI.

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