Utilization of peripheral nerve feedback at a preconscious level.

Introduction: Sensorimotor integration is important, if not required, when using our hands. The integration of the tactile and motor systems is disrupted in individuals with upper limb amputations because their connection to their fingertips is lost. Direct cortical stimulation allows for modality and location matched perceptions; however, studies show that the time to process and act upon direct cortical feedback significantly exceeds the time to do the same with naturally produced tactile feedback. Direct cortical stimulation does not engage multiple parallel structures in the brain stem meant to integrate tactile feedback with signals from the motor system at a sub-perceptual or pre-perceptual level before the somatosensory cortex is involved. While reasonable to assume, it is not known if the artificially generated signals will engage the same peripheral tactile pathways to the pre-perceptual and perceptual structures as natural tactile sensation. Our hypothesis is that pre-perceptual structures will process the electrically generated neural activity as it would naturally generated neural activity. Methods: In this study, stimulation of the median nerve in multiple subjects' residual limbs produced modal, and location matched sensory perceptions in their hands. We found the time to process different stimuli using simple reaction time tests in three different formats. Results: We showed the minimum time to process peripheral nerve stimulation and initiate a motor plan is similar to naturally generated tactile feedback and is processed upwards of 50 - 175 ms faster than visual feedback alone. We also found the effect of stimulation intensity on the rate of feedback processing follows the same trend of natural sensory feedback, Piéron's law indicating that the unimodal processing of PNS is similar to natural touch. Finally, we found that tactile feedback given to a pre-perceptual level is again used in the motor plan. Discussion: Taken together, we conclude that peripheral nerve stimulation engages the pre-perceptual pathways of the brain, and hence demonstrate advantages of peripheral restoration of sensory inputs.

Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration After Tetraplegia.

BACKGROUND AND OBJECTIVES: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. METHODS: A 27-year-old right-handed man with AIS-B (motor-complete, sensory-incomplete) C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of using a brain-machine interface to read from and write to the brain for restoring motor and sensory functions of the participant's own arm and hand. RESULTS: Multiunit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions, resulting in functional movements that the participant was able to command under brain control to perform virtual and actual arm and hand movements. The system was well tolerated with no operative complications. CONCLUSION: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to create bidirectional restoration of motor and sensory functions of the arm and hand after neurological injury.

Distally-referred surface electrical nerve stimulation (DR-SENS) for haptic feedback.

Objective.This study's objective is to understand distally-referred surface electrical nerve stimulation (DR-SENS) and evaluates the effects of electrode placement, polarity, and stimulation intensity on the location of elicited sensations in non-disabled individuals.Approach.A two-phased human experiment was used to characterize DR-SENS. In Experiment One, we explored 182 electrode combinations to identify a subset of electrode position combinations that would be most likely to elicit distally-referred sensations isolated to the index finger without discomfort. In Experiment Two, we further examined this subset of electrode combinations to determine the effect of stimulation intensity and electrode position on perceived sensation location. Stimulation thresholds were evaluated using parameter estimation by sequential testing and sensation locations were characterized using psychometric intensity tests.Main Results.We found that electrode positions distal to the wrist can consistently evoke distally referred sensations with no significant polarity dependency. The finger-palm combination had the most occurrences of distal sensations, and the different variations of this combination did not have a significant effect on sensation location. Increasing stimulation intensity significantly expanded the area of the sensation, moved the most distal sensation distally, and moved the vertical centroid proximally. Also, a large anodic-leading electrode at the elbow mitigated all sensation at the anodic-leading electrode site while using symmetric stimulation waveforms. Furthermore, this study showed that the most intense sensation for a given percept can be distally referred. Lastly, for each participant, at least one of the finger-palm combinations evaluated in this study worked at both perception threshold and maximum comfortable stimulation intensities.Significance.These findings show that a non-invasive surface electrical stimulation charge modulated haptic interface can be used to elicit distally-referred sensations on non-disabled users. Furthermore, these results inform the design of novel haptic interfaces and other applications of surface electrical stimulation based haptic feedback on electrodes positioned distally from the wrist.

Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration after Tetraplegia.

Background: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. Objective: We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. Methods: A right-handed man with motor-complete C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of a bidirectional brain-machine interface to restore function of the participant's own arm and hand. Results: Multi-unit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions. The system was well tolerated with no operative complications. Conclusion: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to allow restoration of motor and sensory functions of the arm and hand after neurological injury.

Restoration of sensory information via bionic hands.

Individuals who have lost the use of their hands because of amputation or spinal cord injury can use prosthetic hands to restore their independence. A dexterous prosthesis requires the acquisition of control signals that drive the movements of the robotic hand, and the transmission of sensory signals to convey information to the user about the consequences of these movements. In this Review, we describe non-invasive and invasive technologies for conveying artificial sensory feedback through bionic hands, and evaluate the technologies' long-term prospects.

Toward higher-performance bionic limbs for wider clinical use.

Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs.

Biomechanical characterization of isolated epineurial and perineurial membranes of rabbit sciatic nerve.

Design of interface devices for effective, long-term integration into neural tissue is dependent on the biomechanical properties of the nerve membranes. Within the peripheral nerve, the two relevant connective tissue layers for interfacing are the epineurium and perineurium. Previous work has reported the forces needed to penetrate the whole nerve, but the mechanical differences between epineurium and perineurium were not reported. Design of intraneural electrodes that place electrodes within the nerve requires knowledge of the mechanics of individual tissues. This study quantified the Young's moduli and ultimate strains of the perineurium and the epineurium separately. We also measured the forces necessary to penetrate each tissue in isolation. We used a custom-built microtensile testing device to measure the Young's modulus values. The measured Young's moduli of the epineurium and the perineurium was 0.4 ± 0.1 MPa and 3.0 ± 0.3 MPa, respectively. We also measured the force required for blunt and sharp stainless steel, 100 µm diameter probes to be inserted into isolated epineurial tissue and perineurial tissue at 2 mm/s. These data provide additional guidelines for selection of materials for long-term implants that best match the tissue properties. The results will guide neural interface design such that electrodes can be placed through either the epineurium alone or both the epineurium and perineurium.

Frequency Shapes the Quality of Tactile Percepts Evoked through Electrical Stimulation of the Nerves.

Electrical stimulation of the peripheral nerves of human participants provides a unique opportunity to study the neural determinants of perceptual quality using a causal manipulation. A major challenge in the study of neural coding of touch has been to isolate the role of spike timing-at the scale of milliseconds or tens of milliseconds-in shaping the sensory experience. In the present study, we address this question by systematically varying the pulse frequency (PF) of electrical stimulation pulse trains delivered to the peripheral nerves of seven participants with upper and lower extremity limb loss via chronically implanted neural interfaces. We find that increases in PF lead to systematic increases in perceived frequency, up to ∼50 Hz, at which point further changes in PF have little to no impact on sensory quality. Above this transition frequency, ratings of perceived frequency level off, the ability to discriminate changes in PF is abolished, and verbal descriptors selected to characterize the sensation change abruptly. We conclude that sensation quality is shaped by temporal patterns of neural activation, even if these patterns are imposed on a fixed neural population, but this temporal patterning can only be resolved up to ∼50 Hz. These findings highlight the importance of spike timing in shaping the quality of a sensation and will contribute to the development of encoding strategies for conveying touch feedback through bionic hands and feet.SIGNIFICANCE STATEMENT A major challenge in the study of neural coding of touch has been to understand how temporal patterns in neuronal responses shape the sensory experience. We address this question by varying the pulse frequency (PF) of electrical pulse trains delivered through implanted nerve interfaces in seven amputees. We concomitantly vary pulse width to separate the effect of changing PF on sensory quality from its effect on perceived magnitude. We find that increases in PF lead to increases in perceived frequency, a qualitative dimension, up to ∼50 Hz, beyond which changes in PF have little impact on quality. We conclude that temporal patterning in the neuronal response can shape quality and discuss the implications for restoring touch via neural interfaces.

Comparison of Myoelectric Control Schemes for Simultaneous Hand and Wrist Movement using Chronically Implanted Electromyography: A Case Series.

OBJECTIVE: A current biomedical engineering challenge is the development of a system that allows fluid control of multi-functional prosthetic devices through a human-machine interface. Here we probe this challenge by studying two subjects with trans-radial limb loss as they control a virtual hand and wrist system using 6 or 8 chronically implanted intramuscular electromyographic (iEMG) signals. The subjects successfully controlled a 4, 5, and 6 Degrees of Freedom (DoF's) virtual hand and wrist systems to perform a target matching task. APPROACH: Two control systems were evaluated where one tied EMG features directly to movement directions (Direct Control) and the other method determines user intent in the context of prior training data (Linear Interpolation). MAIN RESULTS: Subjects successfully matched most targets with both controllers but differences were seen as the complexity of the virtual limb system increased. The Direct Control method encountered difficulty due to crosstalk at higher DoF's. The Linear Interpolation method reduced crosstalk effects and outperformed Direct Control at higher DoF's. This work also studied the use of the Postural Control Algorithm to control the hand postures simultaneously with wrist degrees of freedom. SIGNIFICANCE: This work presents preliminary evidence that the PC algorithm can be used in conjunction with wrist control, that Direct Control with iEMG signals allows stable 4-DoF control, and that EMG pre-processing using the Linear Interpolation method can improve performance at 5 and 6-DoF's.

Directed stimulation with interfascicular interfaces for peripheral nerve stimulation.

Objective.Computational models have shown that directional electrical contacts placed within the epineurium, between the fascicles, and not penetrating the perineurium, can achieve selectivity levels similar to point source contacts placed within the fascicle. The objective of this study is to test, in a murine model, the hypothesis that directed interfascicular contacts are selective.Approach.Multiple interfascicular electrodes with directional contacts, exposed on a single face, were implanted in the sciatic nerves of 32 rabbits. Fine-wire intramuscular wire electrodes were implanted to measure electromyographic (EMG) activity from medial and lateral gastrocnemius, soleus, and tibialis anterior muscles.Main results.The recruitment data demonstrated that directed interfascicular interfaces, which do not penetrate the perineurium, selectively activate different axon populations.Significance.Interfascicular interfaces that are inside the nerve, but do not penetrate the perineurium are an alternative to intrafascicular interfaces and may offer additional selectivity compared to extraneural approaches.

Stable, simultaneous and proportional 4-DoF prosthetic hand control via synergy-inspired linear interpolation: a case series.

BACKGROUND: Current commercial prosthetic hand controllers limit patients' ability to fully engage high Degree-of-Freedom (DoF) prosthetic hands. Available feedforward controllers rely on large training data sets for controller setup and a need for recalibration upon prosthesis donning. Recently, an intuitive, proportional, simultaneous, regression-based 3-DoF controller remained stable for several months without retraining by combining chronically implanted electromyography (ciEMG) electrodes with a K-Nearest-Neighbor (KNN) mapping technique. The training dataset requirements for simultaneous KNN controllers increase exponentially with DoF, limiting the realistic development of KNN controllers in more than three DoF. We hypothesize that a controller combining linear interpolation, the muscle synergy framework, and a sufficient number of ciEMG channels (at least two per DoF), can allow stable, high-DoF control. METHODS: Two trans-radial amputee subjects, S6 and S8, were implanted with percutaneously interfaced bipolar intramuscular electrodes. At the time of the study, S6 and S8 had 6 and 8 bipolar EMG electrodes, respectively. A Virtual Reality (VR) system guided users through single and paired training movements in one 3-DoF and four different 4-DoF cases. A linear model of user activity was built by partitioning EMG feature space into regions bounded by vectors of steady state movement EMG patterns. The controller evaluated online EMG signals by linearly interpolating the movement class labels for surrounding trained EMG movements. This yields a simultaneous, continuous, intuitive, and proportional controller. Controllers were evaluated in 3-DoF and 4-DoF through a target-matching task in which subjects controlled a virtual hand to match 80 targets spanning the available movement space. Match Percentage, Time-To-Target, and Path Efficiency were evaluated over a 10-month period based on subject availability. RESULTS AND CONCLUSIONS: In 3-DoF, S6 and S8 matched most targets and demonstrated stable control after 8 and 10 months, respectively. In 4-DoF, both subjects initially found two of four 4-DoF controllers usable, matching most targets. S8 4-DoF controllers were stable, and showed improving trends over 7-9 months without retraining or at-home practice. S6 4-DoF controllers were unstable after 7 months without retraining. These results indicate that the performance of the controller proposed in this study may remain stable, or even improve, provided initial viability and a sufficient number of EMG channels. Overall, this study demonstrates a controller capable of stable, simultaneous, proportional, intuitive, and continuous control in 3-DoF for up to ten months and in 4-DoF for up to nine months without retraining or at-home use with minimal training times.

Chronic nerve health following implantation of femoral nerve cuff electrodes.

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

Ambulatory searching task reveals importance of somatosensation for lower-limb amputees.

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

Combination of Simultaneous Artificial Sensory Percepts to Identify Prosthetic Hand Postures: A Case Study.

Multiple sources of sensory information are combined to develop hand posture percepts in the intact system, but the combination of multiple artificial somatosensory percepts by human prosthesis users has not been studied. Here, we report on a case study in which a person with transradial amputation identified prosthetic hand postures using artificial somatosensory feedback. He successfully combined five artificial somatosensory percepts to achieve above-chance performance of 95.0% and 75.7% in identifying four and seven postures, respectively. We studied how artificial somatosensation and the extant hand representation are combined in the decision-making process by providing two mappings between the prosthetic sensor and the location of the sensory percept: (1) congruent, and (2) incongruent. The participant's ability to combine and engage with the sensory feedback significantly differed between the two conditions. The participant was only able to successfully generalize prior knowledge to novel postures in the congruent mapping. Further, he learned postures more accurately and quickly in the congruent mapping. Finally, he developed an understanding of the relationships between postures in the congruent mapping instead of simply memorizing each individual posture. These experimental results are corroborated by a Bayesian decision-making model which tracked the participant's learning.

Implanted High Density Cuff Electrodes Functionally Activate Human Tibial and Peroneal Motor Units Without Chronic Detriment to Peripheral Nerve Health.

OBJECTIVE: Peripheral nerve stimulation via multi-contact nerve cuff electrodes (NCEs) has proved effective in restoring function to individuals with lower-extremity paralysis. This study investigates clinical measures of nerve health over one year post-implantation of a composite flat-interface nerve electrode (C-FINE) on the tibial and peroneal nerves above the knee in a human volunteer. This represents the first deployment of a novel NCE on new neural targets in a uniquely challenging location prone to prolonged externally applied forces, making acute and chronic postoperative observation critical. MATERIALS AND METHODS: A 27-year-old man with an incomplete spinal cord injury (AIS C) at the C3 to C4 level received eight-contact C-FINEs bilaterally on the tibial and peroneal nerves, proximal to the knee. Access to four contacts per cuff exhibiting the most desirable responses was externalized via temporary percutaneous leads. Percutaneous leads were later removed, with contacts generating the best dorsiflexion (two of four) and plantar flexion (one of four) reconnected to a permanently implanted pulse generator. For 13 months post-implantation, nerve health and cuff performance were assessed through motor nerve conduction velocity (MNCV) studies, clinical needle electromyography, compound motor action potential (CMAP), sensory nerve action potential (SNAP), stimulation-evoked tetanic moment collection, and lower-limb circumference measurements. RESULTS: Tibial and peroneal MNCVs remained stable bilaterally above 40 m/sec, with CMAPs increased or stable after six months. SNAPs remained stable across all measurements. CMAP initial charge thresholds remained below 50 nC, with minimal changes to muscle recruitment order in three of four externalized contacts per cuff. Peak tetanic moments remained stable, with bilateral increases in thigh and calf circumferences of 5% and 14% over one year. CONCLUSIONS: Above-knee tibial and peroneal NCEs can restore stimulated ankle-joint function without chronic nerve health detriments. Alongside previous femoral nerve data, this study demonstrates the ability of NCEs to enhance lower-extremity function with limited neuromuscular impact.

Selective Nerve Cuff Stimulation Strategies for Prolonging Muscle Output.

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

Stable, three degree-of-freedom myoelectric prosthetic control via chronic bipolar intramuscular electrodes: a case study.

BACKGROUND: Modern prosthetic hands are typically controlled using skin surface electromyographic signals (EMG) from remaining muscles in the residual limb. However, surface electrode performance is limited by changes in skin impedance over time, day-to-day variations in electrode placement, and relative motion between the electrodes and underlying muscles during movement: these limitations require frequent retraining of controllers. In the presented study, we used chronically implanted intramuscular electrodes to minimize these effects and thus create a more robust prosthetic controller. METHODS: A study participant with a transradial amputation was chronically implanted with 8 intramuscular EMG electrodes. A K Nearest Neighbor (KNN) regression velocity controller was trained to predict intended joint movement direction using EMG data collected during a single training session. The resulting KNN was evaluated over 12 weeks and in multiple arm posture configurations, with the participant controlling a 3 Degree-of-Freedom (DOF) virtual reality (VR) hand to match target VR hand postures. The performance of this EMG-based controller was compared to a position-based controller that used movement measured from the participant's opposite (intact) hand. Surface EMG was also collected for signal quality comparisons. RESULTS: Signals from the implanted intramuscular electrodes exhibited less crosstalk between the various channels and had a higher Signal-to-Noise Ratio than surface electrode signals. The performance of the intramuscular EMG-based KNN controller in the VR control task showed no degradation over time, and was stable over the 6 different arm postures. Both the EMG-based KNN controller and the intact hand-based controller had 100% hand posture matching success rates, but the intact hand-based controller was slightly superior in regards to speed (trial time used) and directness of the VR hand control (path efficiency). CONCLUSIONS: Chronically implanted intramuscular electrodes provide negligible crosstalk, high SNR, and substantial VR control performance, including the ability to use a fixed controller over 12 weeks and under different arm positions. This approach can thus be a highly effective platform for advanced, multi-DOF prosthetic control.

Intraoperative Responses May Predict Chronic Performance of Composite Flat Interface Nerve Electrodes on Human Femoral Nerves.

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

Neural engineering: the process, applications, and its role in the future of medicine.

OBJECTIVE: Recent advances in neural engineering have restored mobility to people with paralysis, relieved symptoms of movement disorders, reduced chronic pain, restored the sense of hearing, and provided sensory perception to individuals with sensory deficits. APPROACH: This progress was enabled by the team-based, interdisciplinary approaches used by neural engineers. Neural engineers have advanced clinical frontiers by leveraging tools and discoveries in quantitative and biological sciences and through collaborations between engineering, science, and medicine. The movement toward bioelectronic medicines, where neuromodulation aims to supplement or replace pharmaceuticals to treat chronic medical conditions such as high blood pressure, diabetes and psychiatric disorders is a prime example of a new frontier made possible by neural engineering. Although one of the major goals in neural engineering is to develop technology for clinical applications, this technology may also offer unique opportunities to gain insight into how biological systems operate. MAIN RESULTS: Despite significant technological progress, a number of ethical and strategic questions remain unexplored. Addressing these questions will accelerate technology development to address unmet needs. The future of these devices extends far beyond treatment of neurological impairments, including potential human augmentation applications. Our task, as neural engineers, is to push technology forward at the intersection of disciplines, while responsibly considering the readiness to transition this technology outside of the laboratory to consumer products. SIGNIFICANCE: This article aims to highlight the current state of the neural engineering field, its links with other engineering and science disciplines, and the challenges and opportunities ahead. The goal of this article is to foster new ideas for innovative applications in neurotechnology.