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.

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.

Visuotactile synchrony of stimulation-induced sensation and natural somatosensation.

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

Home Use of a Neural-connected Sensory Prosthesis Provides the Functional and Psychosocial Experience of Having a Hand Again.

The loss of a hand has many psychosocial repercussions. While advanced multi-articulated prostheses can improve function, without sensation, they cannot restore the full experience and connection of a hand. Direct nerve interfaces can restore naturalistic sensation to amputees. Our sensory restoration system produced tactile and proprioceptive sensations on the hand via neural stimulation through chronically implanted electrodes. In this study, upper limb amputees used a sensory-enabled prosthesis in their homes and communities, autonomously and unconstrained to specific tasks. These real-life conditions enabled us to study the impact of sensation on prosthetic usage, functional performance, and psychosocial experience. We found that sensory feedback fundamentally altered the way participants used their prosthesis, transforming it from a sporadically-used tool into a readily and frequently-used hand. Functional performance with sensation improved following extended daily use. Restored sensation improved a wide range of psychosocial factors, including self-efficacy, prosthetic embodiment, self-image, social interaction, and quality of life. This study demonstrates that daily use of a sensory-enabled prosthesis restores the holistic experience of having a hand and more fully reconnects amputees with the world.

Sensory adaptation to electrical stimulation of the somatosensory nerves.

OBJECTIVE: Sensory systems adapt their sensitivity to ambient stimulation levels to improve their responsiveness to changes in stimulation. The sense of touch is also subject to adaptation, as evidenced by the desensitization produced by prolonged vibratory stimulation of the skin. Electrical stimulation of nerves elicits tactile sensations that can convey feedback for bionic limbs. In this study, we investigate whether artificial touch is also subject to adaptation, despite the fact that the peripheral mechanotransducers are bypassed. APPROACH: Using well-established psychophysical paradigms, we characterize the time course and magnitude of sensory adaptation caused by extended electrical stimulation of the residual somatosensory nerves in three human amputees implanted with cuff electrodes. MAIN RESULTS: We find that electrical stimulation of the nerve also induces perceptual adaptation that recovers after cessation of the stimulus. The time course and magnitude of electrically-induced adaptation are equivalent to their mechanically-induced counterparts. SIGNIFICANCE: We conclude that, in natural touch, the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations. Further, as it does for native hands, adaptation confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

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

Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees.

OBJECTIVE: Stability and selectivity are important when restoring long-term, functional sensory feedback in individuals with limb-loss. Our objective is to demonstrate a chronic, clinical neural stimulation system for providing selective sensory response in two upper-limb amputees. APPROACH: Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of the upper-limb. MAIN RESULTS: Nerve stimulation produced a selective sensory response on 19 of 20 contacts and 16 of 16 contacts in subjects 1 and 2, respectively. Stimulation elicited multiple, distinct percept areas on the phantom and residual limb. Consistent threshold, impedance, and percept areas have demonstrated that the neural interface is stable for the duration of this on-going, chronic study. SIGNIFICANCE: We have achieved selective nerve response from multi-contact cuff electrodes by demonstrating characteristic percept areas and thresholds for each contact. Selective sensory response remains consistent in two upper-limb amputees for 1 and 2 years, the longest multi-contact sensory feedback system to date. Our approach demonstrates selectivity and stability can be achieved through an extraneural interface, which can provide sensory feedback to amputees.

Paced glottic closure for controlling aspiration pneumonia in patients with neurologic deficits of various causes.

OBJECTIVES: We undertook to determine whether paced vocal fold adduction can check aspiration in patients with various neurologic conditions. METHODS: Five patients with fluoroscopically documented aspiration and repeated pneumonias were enrolled. Two previously reported patients with hemispheric stroke were compared to 3 additional subjects with brain stem-basal ganglia and cerebellar stroke, cerebral palsy, and multiple sclerosis. A modified Vocare stimulator was implanted subcutaneously and linked to the ipsilateral recurrent laryngeal nerve via perineural electrodes. Vocal fold adduction and glottic closure were effected with pulse trains (42 Hz; 1.2 mA; 188 to 560 micros) and recorded with Enhanced Image J. Fluoroscopy results with and without stimulation were assessed by 2 independent blinded reviewers. Pneumonia rates were compared before, during, and after the 6- to 12-month enrollment periods. RESULTS: There was statistically significant vocal fold adduction (p < 0.05) for all patients, further verified with bolus arrest (p < 0.05 for thin liquids, thick liquids, and puree depending on the speech-language pathologist). Pneumonia was prevented in 4 of the 5 patients during enrollment. In the fifth patient, who had brain stem-basal ganglia and cerebellar stroke, we were unable to completely seal the glottis and open the cricopharyngeus enough to handle his secretions. CONCLUSIONS: Vocal fold pacing for aspiration pneumonia from a variety of neurologic insults appears to be appropriate as long as the glottis can be sealed. It is not sufficient when the cricopharyngeus must be independently opened.

Stimulation stability and selectivity of chronically implanted multicontact nerve cuff electrodes in the human upper extremity.

Nine spiral nerve cuff electrodes were implanted in two human subjects for up to three years with no adverse functional effects. The objective of this study was to look at the long term nerve and muscle response to stimulation through nerve cuff electrodes. The nerve conduction velocity remained within the clinically accepted range for the entire testing period. The stimulation thresholds stabilized after approximately 20 weeks. The variability in the activation over time was not different from muscle-based electrodes used in implanted functional electrical stimulation systems. Three electrodes had multiple, independent contacts to evaluate selective recruitment of muscles. A single muscle could be selectively activated from each electrode using single-contact stimulation and the selectivity was increased with the use of field steering techniques. The selectivity after three years was consistent with selectivity measured during the implant surgery. Nerve cuff electrodes are effective for chronic muscle activation and multichannel functional electrical stimulation in humans.

Standing after spinal cord injury with four-contact nerve-cuff electrodes for quadriceps stimulation.

This paper describes the performance of a 16-channel implanted neuroprosthesis for standing and transfers after spinal cord injury including four-contact nerve-cuff electrodes stimulating the femoral nerve for knee extension. Responses of the nerve-cuffs were stable and standing times increased by 600% over time-matched values with a similar eight-channel neuroprosthesis utilizing muscle-based electrodes on vastus lateralis for knee extension.

Artificial manipulation of voice in the human by an implanted stimulator.

OBJECTIVES/HYPOTHESIS: Traditional approaches influencing voice quality (e.g., anatomical and chemical denervation for spasmodic dysphonia, surgical medialization for paralysis) have ignored the dynamic nature of the larynx. STUDY DESIGN: We report here the first attempt to manipulate voice using an implanted stimulator to systematically control vocal fold adduction. METHODS: Devices placed for aspiration in three subjects retaining speech after stroke, cerebral palsy, and multiple sclerosis were used to stimulate recurrent laryngeal nerves with 42 Hz, 52 to 200 microsecond pulses of incremental amplitudes during phonation with the tracheostomy tube occluded. Vocal fold adduction increased with stimulation strength (P < .05). Speech was analyzed with the Vox Metria program. RESULTS: We found highly significant differences for fundamental frequency (P < .007), jitter (P < .004), and shimmer (P < .005), between natural and stimulated voice (aah and eeh) when using higher charges. CONCLUSIONS: Dynamic vocal fold manipulation seems promising in terms of versatility lacking with static approaches to voice control.

A model of selective activation of the femoral nerve with a flat interface nerve electrode for a lower extremity neuroprosthesis.

Functional electrical stimulation (FES) can restore limb movements through electrically initiated, coordinated contractions of paralyzed muscles. The peripheral nerve is an attractive site for stimulation using cuff electrodes. Many applications will require the electrode to selectively activate many smaller populations of axons within a common nerve trunk. The purpose of this study is to computationally model the performance of a flat interface nerve electrode (FINE) on the proximal femoral nerve for standing and stepping applications. Simulations investigated multiple FINE configurations to determine the optimal number and locations of contacts for the maximum muscular selectivity. Realistic finite element method (FEM) models were developed from digitized cross sections from cadaver femoral nerve specimens. Electrical potentials were calculated and interpolated voltages were applied to a double-cable axon model. Model output was analyzed to determine selectivity and estimate joint moments with a musculoskeletal model. Simulations indicated that a 22-contact FINE will produce the greatest selectivity. Simulations predicted that an eight-contact FINE can be expected to selectively stimulate each of the six muscles innervated by the proximal femoral nerve, producing a sufficient knee extension moment for the sit-to-stand transition and contributing 60% of the hip flexion moment needed during gait. We conclude that, whereas more contacts produce greater selectivity, eight channels are sufficient for standing and stepping with an FES system using a FINE on the common femoral nerve.

Fascicular perineurium thickness, size, and position affect model predictions of neural excitation.

The number of applications using neural prosthetic interfaces is expanding. Computer models are a valuable tool to evaluate stimulation techniques and electrode designs. Although our understanding of neural anatomy has improved, its impact on the effects of neural stimulation is not well understood. This study evaluated the effects of fascicle perineurial thickness, diameter, and position on axonal excitation thresholds and population recruitment using finite element models and NEURON simulations. The perineurial thickness of human fascicles was found to be 3.0% +/- 1.0% of the fascicle diameter. Increased perineurial thickness and fascicle diameter increased activation thresholds. The presence of a large neighboring fascicle caused a significant change in activation of a smaller target fascicle by as much as 80% +/- 11% of the total axon population. Smaller fascicles were recruited at lower amplitudes than neighboring larger fascicles. These effects were further illustrated in a realistic model of a human femoral nerve surrounded by a nerve cuff electrode. The data suggest that fascicular selectivity is strongly dependent upon the anatomy of the nerve being stimulated. Therefore, accurate representations of nerve anatomy are required to develop more accurate computer models to evaluate and optimize nerve electrode designs for neural prosthesis applications.

Human nerve stimulation thresholds and selectivity using a multi-contact nerve cuff electrode.

Testing of the recruitment properties and selective activation capabilities of a multi-contact spiral nerve cuff electrode was performed intraoperatively in 21 human subjects. The study was conducted in two phases. An exploratory phase with ten subjects gave a preliminary overview of the data and data collection process and a systematic phase with eleven subjects provided detailed recruitment properties. The mean stimulation threshold of 25 +/- 17 nC was not significantly different than previous studies in animal models but much lower than muscle electrodes. The selectivity, defined as the percent of total activation of the first muscle recruited before another muscle reached threshold, ranged from 27% to 97% with a mean of 55%. In each case, the muscle that was selectively activated was the first muscle to branch distal to the cuff location. This study serves as a preliminary evaluation of nerve cuff electrodes in humans prior to chronic implant in subjects with high tetraplegia.

Spiral nerve cuff electrodes for an upper extremity neuroprosthesis.

Four nerve cuff electrodes were implanted in the shoulder and arm of one subject with high tetraplegia. Stimulation produced shoulder abduction, elbow flexion and extension, and wrist and finger extension. Recruitment properties were quantified using twitch EMG recruitment curves and tetanic moment measurements. The chronic qualitative 'function' of each channel of stimulation could be predicted from the intraoperative data collection. The average threshold was 11.3 +/- 9 nC and stabilized to this value over the 35 weeks of testing. The moment production of most muscles increased over the testing period due to exercise of the atrophied muscles. No muscle decreased its moment and most appeared to plateau after 15 weeks. Sensation was also evaluated since this subject had an incomplete injury and nerve stimulation was not found to painful throughout the range of muscle activation. Nerve electrodes have been shown to be a stable, effective means of activating muscles for neuroprosthetics.

Functionally selective peripheral nerve stimulation with a flat interface nerve electrode.

One of the important goals of peripheral nerve electrode development is to design an electrode for selective recruitment of the different functions of a common nerve trunk. A challenging task is gaining selective access to central axon populations. In this paper, a simple electrode that takes advantage of the neural plasticity to reshape the nerve is presented. The flat interface nerve electrode (FINE) reshapes the nerve into a flat geometry to increase the surface area and move central axon populations close to the surface. The electrode was implanted acutely on the sciatic nerve of eight cats. The FINE can significantly reshape the nerve and fascicles (p < 0.0001) while maintaining the same total nerve cross-sectional area. The stimulation thresholds were 2.89 nC for pulse amplitude modulation and 10.2 nC for pulse-width modulation. Monopolar, square-pulse stimulation with single contacts on the FINE selectively recruited each of the four main branches of the sciatic nerve. Simultaneous stimulation with two contacts produced moments about the ankle joint that were a combination of the moments produced by the individual contacts when stimulated separately.