Utah Slanted Electrode Arrays Research Articles

Development of a feline model for preclinical research of a new translabyrinthine auditory nerve implant.

Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers. Cochlear implants also cannot be implanted in some individuals with an obstruction or severe malformations of the cochlea. Alternatively, intraneural stimulation delivered via an auditory nerve implant could provide direct contact with neural fibers and thus reduce unwanted current spread. More confined current during stimulation can increase selectivity of frequency fiber activation. Furthermore, devices such as the Utah Slanted Electrode Array can provide access to the full cross section of the auditory nerve, including low frequency fibers that are difficult to reach using a cochlear implant. However, further scientific and preclinical research of these Utah Slanted Electrode Array devices is limited by the lack of a chronic large animal model for the auditory nerve implant, especially one that leverages an appropriate surgical approach relevant for human translation. This paper presents a newly developed transbullar translabyrinthine surgical approach for implanting the auditory nerve implant into the cat auditory nerve. In our first of a series of studies, we demonstrate a surgical approach in non-recovery experiments that enables implantation of the auditory nerve implant into the auditory nerve, without damaging the device and enabling effective activation of the auditory nerve fibers, as measured by electrode impedances and electrically evoked auditory brainstem responses. These positive results motivate performing future chronic cat studies to assess the long-term stability and function of these auditory nerve implant devices, as well as development of novel stimulation strategies that can be translated to human patients.

Evaluation of Pneumatic Insertion Stability of Utah Slanted Electrode Arrays in Rat Sciatic Nerve.

The Utah Electrode Array (UEA) and its variants (e.g., the Utah Slanted Electrode Array, or USEA) have been prominent contributors to advances in the field of neural engineering over the past decade. The most common means of inserting UEA and USEA devices into neural tissue is pneumatic insertion performed by an insertion wand and a pneumatic controller. As design changes from the well-established standards occur to better suit specialized surgical applications, it becomes essential to verify that the alterations do not compromise the structural integrity of the device during insertion. This paper characterizes and demonstrates the reliability of specialized USEAs and insertion wands designed for auditory nerve implants following pneumatic insertion into a rat sciatic nerve. The results show that proposed changes in the USEA form factor and pneumatic insertion ergonomics do not compromise implant stability and device structural viability.

Discriminability of multiple cutaneous and proprioceptive hand percepts evoked by intraneural stimulation with Utah slanted electrode arrays in human amputees

BackgroundElectrical stimulation of residual afferent nerve fibers can evoke sensations from a missing limb after amputation, and bionic arms endowed with artificial sensory feedback have been shown to confer functional and psychological benefits. Here we explore the extent to which artificial sensations can be discriminated based on location, quality, and intensity.MethodsWe implanted Utah Slanted Electrode Arrays (USEAs) in the arm nerves of three transradial amputees and delivered electrical stimulation via different electrodes and frequencies to produce sensations on the missing hand with various locations, qualities, and intensities. Participants performed blind discrimination trials to discriminate among these artificial sensations.ResultsParticipants successfully discriminated cutaneous and proprioceptive sensations ranging in location, quality and intensity. Performance was significantly greater than chance for all discrimination tasks, including discrimination among up to ten different cutaneous location-intensity combinations (15/30 successes, p < 0.0001) and seven different proprioceptive location-intensity combinations (21/40 successes, p < 0.0001). Variations in the site of stimulation within the nerve, via electrode selection, enabled discrimination among up to five locations and qualities (35/35 successes, p < 0.0001). Variations in the stimulation frequency enabled discrimination among four different intensities at the same location (13/20 successes, p < 0.0005). One participant also discriminated among individual stimulation of two different USEA electrodes, simultaneous stimulation on both electrodes, and interleaved stimulation on both electrodes (20/24 successes, p < 0.0001).ConclusionElectrode location, stimulation frequency, and stimulation pattern can be modulated to evoke functionally discriminable sensations with a range of locations, qualities, and intensities. This rich source of artificial sensory feedback may enhance functional performance and embodiment of bionic arms endowed with a sense of touch.

Long-term performance of Utah slanted electrode arrays and intramuscular electromyographic leads implanted chronically in human arm nerves and muscles

Objective. We explore the long-term performance and stability of seven percutaneous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human participants as a means to permanently restore sensorimotor function after transradial amputations. Approach. We quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio (SNR) of USEA and iEMG recordings and quantify the stimulation current 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 results. In the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 d (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs across the three participants, the number of functional recording electrodes decreased within the first 2 months after implantation. The SNR 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. Significance. This work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. USEAs provide a rich repertoire of neural recordings and sensory percepts. Although their performance still generally declines over time, functionality can persist long-term. 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.

Intensity Discriminability of Electrocutaneous and Intraneural Stimulation Pulse Frequency in Intact Individuals and Amputees.

Electrical stimulation of residual nerves can be used to provide amputees with intuitive sensory feedback. An important aspect of this artificial sensory feedback is the ability to convey the magnitude of tactile stimuli. Using classical psychophysical methods, we quantified the just-noticeable differences for electrocutaneous stimulation pulse frequency in both intact participants and one transradial amputee. For the transradial amputee, we also quantified the just-noticeable difference of intraneural microstimulation pulse frequency via chronically implanted Utah Slanted Electrode Arrays. We demonstrate that intensity discrimination is similar across conditions: intraneural microstimulation of the residual nerves, electrocutaneous stimulation of the reinnervated skin on the residual limb, and electrocutaneous stimulation of intact hands. We also show that intensity discrimination performance is significantly better at lower pulse frequencies than at higher pulse frequencies - a finding that's unique to electrocutaneous and intraneural stimulation and suggests that supplemental sensory cues may be present at lower pulse frequencies. These results can help guide the implementation of artificial sensory feedback for sensorized bionic arms.Clinical Relevance- Intraneural and electrocutaneous artificial sensory feedback are comparable in their ability to convey the magnitude of tactile stimuli via pulse frequency.

Selective Decrease in Allodynia With High-Frequency Neuromodulation via High-Electrode-Count Intrafascicular Peripheral Nerve Interface After Brachial Plexus Injury

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. 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. 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. 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.

Update on Peripheral Nerve Electrodes for Closed-Loop Neuroprosthetics.

In this paper various types of electrodes for stimulation and recording activity of peripheral nerves for the control of neuroprosthetic limbs are reviewed. First, an overview of interface devices for (feedback-) controlled movement of a prosthetic device is given, after which the focus is on peripheral nervous system (PNS) electrodes. Important electrode properties, i.e., longevity and spatial resolution, are defined based upon the usability for neuroprostheses. The cuff electrode, longitudinal intrafascicular electrodes (LIFE), transverse intrafascicular multichannel electrode (TIME), Utah slanted electrode array (USEA), and the regenerative electrode are discussed and assessed on their longevity and spatial resolution. The cuff electrode seems to be a promising electrode for the control of neuroprostheses in the near future, because it shows the best longevity and good spatial resolution and it has been used on human subjects in multiple studies. The other electrodes may be promising in the future, but further research on their longevity and spatial resolution is needed. A more quantitatively uniform study protocol used for all electrodes would allow for a proper comparison of recording and stimulation performance. For example, the discussed electrodes could be compared in a large in vivo study, using one uniform comparison protocol.

Restoration of motor control and proprioceptive and cutaneous sensation in humans with prior upper-limb amputation via multiple Utah Slanted Electrode Arrays (USEAs) implanted in residual peripheral arm nerves

BackgroundDespite advances in sophisticated robotic hands, intuitive control of and sensory feedback from these prostheses has been limited to only 3-degrees-of-freedom (DOF) with 2 sensory percepts in closed-loop control. A Utah Slanted Electrode Array (USEA) has been used in the past to provide up to 81 sensory percepts for human amputees. Here, we report on the advanced capabilities of multiple USEAs implanted in the residual peripheral arm nerves of human amputees for restoring control of 5 DOF and sensation of up to 131 proprioceptive and cutaneous hand sensory percepts. We also demonstrate that USEA-restored sensory percepts provide a useful source of feedback during closed-loop virtual prosthetic hand control.MethodsTwo 100-channel USEAs were implanted for 4–5 weeks, one each in the median and ulnar arm nerves of two human subjects with prior long-duration upper-arm amputations. Intended finger and wrist positions were decoded from neuronal firing patterns via a modified Kalman filter, allowing subjects to control many movements of a virtual prosthetic hand. Additionally, USEA microstimulation was used to evoke numerous sensory percepts spanning the phantom hand. Closed-loop control was achieved by stimulating via an electrode of the ulnar-nerve USEA while recording and decoding movement via the median-nerve USEA.ResultsSubjects controlled up to 12 degrees-of-freedom during informal, ‘freeform’ online movement decode sessions, and experienced up to 131 USEA-evoked proprioceptive and cutaneous sensations spanning the phantom hand. Independent control was achieved for a 5-DOF real-time decode that included flexion/extension of the thumb, index, middle, and ring fingers, and the wrist. Proportional control was achieved for a 4-DOF real-time decode. One subject used a USEA-evoked hand sensation as feedback to complete a 1-DOF closed-loop virtual-hand movement task. There were no observed long-term functional deficits due to the USEA implants.ConclusionsImplantation of high-channel-count USEAs enables multi-degree-of-freedom control of virtual prosthetic hand movement and restoration of a rich selection of both proprioceptive and cutaneous sensory percepts spanning the hand during the short 4–5 week post-implant period. Future USEA use in longer-term implants and in closed-loop may enable restoration of many of the capabilities of an intact hand while contributing to a meaningful embodiment of the prosthesis.

Linear methods for reducing EMG contamination in peripheral nerve motor decodes.

Signals recorded from the peripheral nervous system (PNS) with high channel count penetrating microelectrode arrays, such as the Utah Slanted Electrode Array (USEA), often have electromyographic (EMG) signals contaminating the neural signal. This common-mode signal source may prevent single neural units from successfully being detected, thus hindering motor decode algorithms. Reducing this EMG contamination may lead to more accurate motor decode performance. A virtual reference (VR), created by a weighted linear combination of signals from a subset of all available channels, can be used to reduce this EMG contamination. Four methods of determining individual channel weights and six different methods of selecting subsets of channels were investigated (24 different VR types in total). The methods of determining individual channel weights were equal weighting, regression-based weighting, and two different proximity-based weightings. The subsets of channels were selected by a radius-based criteria, such that a channel was included if it was within a particular radius of inclusion from the target channel. These six radii of inclusion were 1.5, 2.9, 3.2, 5, 8.4, and 12.8 electrode-distances; the 12.8 electrode radius includes all USEA electrodes. We found that application of a VR improves the detectability of neural events via increasing the SNR, but we found no statistically meaningful difference amongst the VR types we examined. The computational complexity of implementation varies with respect to the method of determining channel weights and the number of channels in a subset, but does not correlate with VR performance. Hence, we examined the computational costs of calculating and applying the VR and based on these criteria, we recommend an equal weighting method of assigning weights with a 3.2 electrode-distance radius of inclusion. Further, we found empirically that application of the recommended VR will require less than 1 ms for 33.3 ms of data from one USEA.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves

Objective. An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Approach. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject’s phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. Main results. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. Significance. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays

For decades, epineurial electrodes have been used in clinical therapies involving the stimulation of peripheral nerves. However, next generation peripheral nerve interfaces for applications such as neuroprosthetics would benefit from an increased ability to selectively stimulate and record from nerve tissue. This increased selectivity may require the use of more invasive devices, such as the Utah Slanted Electrode Array (USEA). Previous research with USEAs has described the histological response to the implantation of these devices in cats and rats; however, no such data has been presented in humans. Therefore, we describe here the degree of penetration and foreign body reaction to USEAs after a four-week implantation period in human median and ulnar nerves. We found that current array designs penetrate a relatively small percentage of the available endoneurial tissue in these large nerves. When electrode tips were located within the endoneurial tissue, labels for axons and myelin were found in close proximity to electrodes. Consistent with other reports, we found activated macrophages attached to explanted devices, as well as within the tissue surrounding the implantation site. Despite this inflammatory response, devices were able to successfully record single- or multi-unit action potentials and elicit sensory percepts. However, modifying device design to allow for greater nerve penetration, as well as mitigating the inflammatory response to such devices, would likely increase device performance and should be investigated in future research.

Acute Monitoring of Genitourinary Function Using Intrafascicular Electrodes: Selective Pudendal Nerve Activity Corresponding to Bladder Filling, Bladder Fullness, and Genital Stimulation

To investigate the use of a microelectrode array with a high spatial density of penetrating intrafascicular electrodes for selective recording of pudendal nerve activity evoked by a variety of genitourinary stimuli. Felines were anesthetized with alpha-chloralose and high-density Utah slanted electrode arrays (48 microelectrodes; 200-μm spacing) were implanted into the pudendal nerve for acute experimentation. Neural activity was recorded during bladder filling, spontaneous reflexive distention-evoked bladder contractions, and tactile somatosensory stimulation. The intrafascicularly implanted pudendal nerve electrodes were able to selectively record neural activity that corresponded to various genitourinary stimuli. Across all seven experimental animals, a total of 10 microelectrodes recorded neural units that were selectively driven by bladder filling or distention-evoked bladder contractions. Twenty-two electrodes were selectively driven by tactile stimulation. Microelectrode arrays implanted intrafascicularly into the pudendal nerve can be used to selectively record the neural responses that reflect bladder status and urogenital tactile stimulation. This work sets the stage for developing future implantable closed-loop neuroprosthetic devices for restoration of bladder function.

Using multiple high-count electrode arrays in human median and ulnar nerves to restore sensorimotor function after previous transradial amputation of the hand.

Peripheral nerve interfaces that can record from and stimulate large numbers of different nerve fibers selectively and independently may help restore intuitive and effective motor and sensory function after hand amputation. To this end, and extending previous work in two subjects, two 100-electrode Utah Slanted Electrode Arrays (USEAs) were implanted for four weeks in the residual ulnar and median nerves of a 50-year-old male whose left, dominant hand had been amputated 21 years previously. Subsequent experiments involved 1) recording from USEAs for real-time control of a virtual prosthetic hand; 2) stimulation to evoke somatosensory percepts; and 3) closed-loop sensorimotor control. Overall, partial motor control and sensation were achieved using USEAs. 1) Isolated action potentials recorded from nerve motor fibers, although sparse at these distal implant sites, were activated during fictive movements of the phantom hand. Unlike in our previous two subjects, electromyographic (EMG) activity contributed to most online recordings and decodes, but was reduced in offline analyses using common average referencing. Online and offline Kalman-filter decodes of thresholded neural or EMG spikes independently controlled different digits of the virtual hand with one or two degrees of freedom. 2) Microstimulation through individual electrodes of the two USEAs evoked up to 106 different percepts, covering much of the phantom hand. The subject discriminated among five perceived stimulus locations, and between two somatosensory submodalities at a single location. 3) USEA-evoked percepts, mimicking contact with either a near or distal virtual target, were used to terminate movements of the virtual hand controlled with USEA recordings comprised wholly or mostly of EMG. These results further indicate that USEAs can help restore sensory and motor function after hand loss.

Behavioral and cellular consequences of high-electrode count Utah Arrays chronically implanted in rat sciatic nerve

Objective. Before peripheral nerve electrodes can be used for the restoration of sensory and motor functions in patients with neurological disorders, the behavioral and histological consequences of these devices must be investigated. These indices of biocompatibility can be defined in terms of desired functional outcomes; for example, a device may be considered for use as a therapeutic intervention if the implanted subject retains functional neurons post-implantation even in the presence of a foreign body response. The consequences of an indwelling device may remain localized to cellular responses at the device-tissue interface, such as fibrotic encapsulation of the device, or they may affect the animal more globally, such as impacting behavioral or sensorimotor functions. The objective of this study was to investigate the overall consequences of implantation of high-electrode count intrafascicular peripheral nerve arrays, High Density Utah Slanted Electrode Arrays (HD-USEAs; 25 electrodes mm−2). Approach. HD-USEAs were implanted in rat sciatic nerves for one and two month periods. We monitored wheel running, noxious sensory paw withdrawal reflexes, footprints, nerve morphology and macrophage presence at the tissue-device interface. In addition, we used a novel approach to contain the arrays in actively behaving animals that consisted of an organic nerve wrap. A total of 500 electrodes were implanted across all ten animals. Main results. The results demonstrated that chronic implantation (⩽8 weeks) of HD-USEAs into peripheral nerves can evoke behavioral deficits that recover over time. Morphology of the nerve distal to the implantation site showed variable signs of nerve fiber degeneration and regeneration. Cytology adjacent to the device-tissue interface also showed a variable response, with some electrodes having many macrophages surrounding the electrodes, while other electrodes had few or no macrophages present. This variability was also seen along the length of the electrodes. Axons remained within the proximity of the electrode tips at the distances required for theoretically effective stimulation and recording (⩽100 μm). Significance. We conclude from these studies that HD-USEAs do not cause overall global effects on the animals, at least up to the two-month period investigated here. These results demonstrate for the first time that the consequences of high-electrode count intrafascicular arrays compare with other peripheral nerve electrodes currently available for clinical or investigational neuromodulation.

Assessment of rat sciatic nerve function following acute implantation of high density utah slanted electrode array (25 electrodes/mm2) based on neural recordings and evoked muscle activity

High density Utah slanted electrode arrays (HD-USEAs) have been developed recently for intrafascicular access to submillimeter neural structures. Insertion of such high electrode density devices may cause nerve crush injury, counteracting the intended improved selective nerve fiber access. HD-USEAs were implanted into sciatic nerves of anesthetized rats. Nerve function was assessed before and after HD-USEA implantation by measuring changes in evoked muscle and nerve compound action potentials and single unit neuronal recordings. Neural activity was recorded with over half of all implanted electrodes. Average decreases of 38%, 36%, and 13% in nerve, medial gastrocnemius, and tibialis anterior compound action potential amplitudes, respectively, were observed following array implantation. Only 1 of 8 implantations resulted in loss of all signals. These studies demonstrate that HD-USEAs provide a useful neural interface without causing a nerve crush injury that would otherwise negate their use in acute preparations (<12 h).

A new high-density (25 electrodes/mm2) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures

Objective. Among the currently available neural interface devices, there has been a need for a penetrating electrode array with a high electrode-count and high electrode-density (the number of electrodes/mm2) that can be used for electrophysiological studies of sub-millimeter neuroanatomical structures. We have developed such a penetrating microelectrode array with both a high electrode-density (25 electrodes/mm2) and high electrode-count (up to 96 electrodes) for small nervous system structures, based on the existing Utah Slanted Electrode Array (USEA). Such high electrode-density arrays are expected to provide greater access to nerve fibers than the conventionally spaced USEA especially in small diameter nerves. Approach. One concern for such high density microelectrode arrays is that they may cause a nerve crush-type injury upon implantation. We evaluated this possibility during acute (<10 h) in vivo experiments with electrode arrays implanted into small diameter peripheral nerves of anesthetized rats (sciatic nerve) and cats (pudendal nerve). Main results. Successful intrafascicular implantation and viable nerve function was demonstrated via microstimulation, single-unit recordings and histological analysis. Measurements of the electrode impedances and quantified electrode dimensions demonstrated fabrication quality. The results of these experiments show that such high density neural interfaces can be implanted acutely into neural tissue without causing a complete nerve crush injury, while mediating intrafascicular access to fibers in small diameter peripheral nerves. Significance. This new penetrating microelectrode array has characteristics un-matched by other neural interface devices currently available for peripheral nervous system neurophysiological research.

Intrafascicular stimulation of monkey arm nerves evokes coordinated grasp and sensory responses

High-count microelectrode arrays implanted in peripheral nerves could restore motor function after spinal cord injury or sensory function after limb loss. In this study, we implanted Utah Slanted Electrode Arrays (USEAs) intrafascicularly at the elbow or shoulder in arm nerves of rhesus monkeys (n = 4) under isoflurane anesthesia. Input-output curves indicated that pulse-width-modulated single-electrode stimulation in each arm nerve could recruit single muscles with little or no recruitment of other muscles. Stimulus trains evoked specific, natural, hand movements, which could be combined via multielectrode stimulation to elicit coordinated power or pinch grasp. Stimulation also elicited short-latency evoked potentials (EPs) in primary somatosensory cortex, which might be used to provide sensory feedback from a prosthetic limb. These results demonstrate a high-resolution, high-channel-count interface to the peripheral nervous system for restoring hand function after neural injury or disruption or for examining nerve structure.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Non-invasive method for selection of electrodes and stimulus parameters for FES applications with intrafascicular arrays

High-channel-count intrafascicular electrode arrays provide comprehensive and selective access to the peripheral nervous system. One practical difficulty in using several electrode arrays to evoke coordinated movements in paralyzed limbs is the identification of the appropriate stimulation channels and stimulus parameters to evoke desired movements. Here we present the use of a six degree-of-freedom load cell placed under the foot of a feline to characterize the muscle activation produced by three 100-electrode Utah Slanted Electrode Arrays (USEAs) implanted into the femoral nerves, sciatic nerves, and muscular branches of the sciatic nerves of three cats. Intramuscular stimulation was used to identify the endpoint force directions produced by 15 muscles of the hind limb, and these directions were used to classify the forces produced by each intrafascicular USEA electrode as flexion or extension. For 451 USEA electrodes, stimulus intensities for threshold and saturation muscle forces were identified, and the 3D direction and linearity of the force recruitment curves were determined. Further, motor unit excitation independence for 198 electrode pairs was measured using the refractory technique. This study demonstrates the utility of 3D endpoint force monitoring as a simple and non-invasive metric for characterizing the muscle-activation properties of hundreds of implanted peripheral nerve electrodes, allowing for electrode and parameter selection for neuroprosthetic applications.

Selective Activation of the Muscles of Micturition Using Intrafascicular Stimulation of the Pudendal Nerve

We investigate the hypothesis that intrafascicular stimulation of the pudendal nerve (PN) can be used to selectively activate the detrusor bladder muscle and the external urethral sphincter (EUS). Nine anesthetized male canines were used in this study. Muscle activations were measured via bladder catheter pressure transducers and EUS electromyography (EMG) wires. The PNs were exposed via dissection of the ischioanal fossa and implanted with Utah Slanted Electrode Arrays (USEAs). USEAs consist of 100, 0.5–1.5 mm long microelectrodes that project out from a 4 $\,\times\,$ 4 mm substrate. Intrafascicular stimulation was delivered via individual USEA microelectrodes in order to map the ability of each electrode to selectively or nonselectively evoke detrusor and/or EUS contractions. We were able to selectively activate the detrusor using 33 Hz stimulation of PN axons with an average of $4.57 \pm 3.82$ ( ${\rm mean }\pm {\rm sd}$ ) USEA electrodes per animal tested. Electrically-evoked and distention-evoked bladder contractions had similar kinetics. Sustained bladder contractions were evoked via 60 s of intrafascicular stimulation. The EUS was activated using 33 Hz stimulation via an average of $26.14 \pm 19.45$ electrodes per animal tested. High frequency ( $> {2}~{\rm kHz}$ ) stimulation delivered via EUS selective electrodes produced nonselective block of PN axons. Examples of how this selective axonal access could be used to restore continence and activate micturition were demonstrated in two animals. We report herein the first study demonstrating selective detrusor and EUS activation via microelectrodes implanted intrafascicularly in the PN. Such selective activation enables new therapeutic possibilities for controlling the muscles of micturition.