Multi-contact Cuff Electrode Research Articles

A soft, scalable and adaptable multi-contact cuff electrode for targeted peripheral nerve modulation

BackgroundCuff electrodes target various nerves throughout the body, providing neuromodulation therapies for motor, sensory, or autonomic disorders. However, when using standard, thick silicone cuffs, fabricated in discrete circular sizes, complications may arise, namely cuff displacement or nerve compression, due to a poor adaptability to variable nerve shapes and sizes encountered in vivo. Improvements in cuff design, materials, closing mechanism and surgical approach are necessary to overcome these issues.MethodsIn this work, we propose a microfabricated multi-channel silicone-based soft cuff electrode with a novel easy-to-implant and size-adaptable design and evaluate a number of essential features such as nerve-cuff contact, nerve compression, cuff locking stability, long-term integration and stimulation selectivity. We also compared performance to that of standard fixed-size cuffs.ResultsThe belt-like cuff made of 150 μm thick silicone membranes provides a stable and pressure-free conformal contact, independently of nerve size variability, combined with a straightforward implantation procedure. The adaptable design and use of soft materials lead to limited scarring and demyelination after 6-week implantation. In addition, multi-contact designs, ranging from 6 to 16 electrodes, allow for selective stimulation in models of rat and pig sciatic nerve, achieving targeted activation of up to 5 hindlimb muscles.ConclusionThese results suggest a promising alternative to classic fixed-diameter cuffs and may facilitate the adoption of soft, adaptable cuffs in clinical settings.

Resource-Efficient Neural Network Architectures for Classifying Nerve Cuff Recordings on Implantable Devices.

Closed-loop functional electrical stimulation can use recorded nerve signals to create implantable systems that make decisions regarding nerve stimulation in real-time. Previous work demonstrated convolutional neural network (CNN) discrimination of activity from different neural pathways recorded by a high-density multi-contact nerve cuff electrode, achieving state-of-the-art performance but requiring too much data storage and power for a practical implementation on surgically implanted hardware. To reduce resource utilization for an implantable implementation, with minimal performance loss for CNNs that can discriminate between neural pathways in multi-contact cuff electrode recordings. Neural networks (NNs) were evaluated using rat sciatic nerve recordings previously collected using 56-channel cuff electrodes to capture spatiotemporal neural activity patterns. NNs were trained to classify individual, natural compound action potentials (nCAPs) elicited by sensory stimuli. Three architectures were explored: the previously reported ESCAPE-NET, a fully convolutional network, and a recurrent neural network. Variations of each architecture were evaluated based on F1-score, number of weights, and floating-point operations (FLOPs). NNs were identified that, when compared to ESCAPE-NET, require 1,132-1,787x fewer weights, 389-995x less memory, and 6-11,073x fewer FLOPs, while maintaining macro F1-scores of 0.70-0.71 compared to a baseline of 0.75. Memory requirements range from 22.69 KB to 58.11 KB, falling within on-chip memory sizes from published deep learning accelerators fabricated in ASIC technology. Reduced versions of ESCAPE-NET require significantly fewer resources without significant accuracy loss, thus can be more easily incorporated into a surgically implantable device that performs closed-loop responsive neural stimulation.

Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk with respect to the functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using micro-computed tomography imaging, we tracked fascicular trajectories and found that, in swine, sensory and motor fascicles are spatially separated cephalad, close to the nodose ganglion, and merge caudad, towards the lower cervical and upper thoracic region; larynx-, heart- and lung-specific fascicles are separated caudad and progressively merge cephalad. Using quantified immunohistochemistry at single fiber level, we identified and characterized all vagal fibers and found that fibers of different morphological types are differentially distributed in fascicles: myelinated afferents and efferents occupy separate fascicles, myelinated and unmyelinated efferents also occupy separate fascicles, and small unmyelinated afferents are widely distributed within most fascicles. We developed a multi-contact cuff electrode to accommodate the fascicular structure of the vagal trunk and used it to deliver fascicle-selective cervical VNS in anesthetized and awake swine. Compound action potentials from distinct fiber types, and physiological responses from different organs, including laryngeal muscle, cough, breathing, and heart rate responses are elicited in a radially asymmetric manner, with consistent angular separations that agree with the documented fascicular organization. These results indicate that fibers in the trunk of the vagus nerve are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.

Influence of the H-reflex on the selectivity of recruitment using multi-contact epineural stimulation of the median nerve in a participant with complete tetraplegia.

Multi-contact epineural electrical stimulation is a technique that can be used to restore grip movements in people with complete tetraplegia. However, neural stimulation can induce undesired H-reflex. This reflex is known to induce a global lower recruitment threshold together with a steepest recruitment curve leading to a degraded selective response. In this study, during stimulation of the median nerve using a multi-contact cuff electrode, a H-reflex response was observed for one muscle (the pronator teres i.e. PT) among the five recorded. As both M-wave and H-wave were separately recorded, we compared the changes of recruitment, recruitment order and se-lectivity with and without the H-reflex and found that blocking the reflex would have enhance the selectivity and increase the range of the intensity amplitude while providing a higher level of gripping force. Thus, blocking H-reflex is an important issue to further enhance epineural multicontact selective stimulation.

Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

Selective neural electrical stimulation restores hand and forearm movements in individuals with complete tetraplegia

BackgroundWe hypothesized that a selective neural electrical stimulation of radial and median nerves enables the activation of functional movements in the paralyzed hand of individuals with tetraplegia. Compared to previous approaches for which up to 12 muscles were targeted through individual muscular stimulations, we focused on minimizing the number of implanted electrodes however providing almost all the needed and useful hand movements for subjects with complete tetraplegia.MethodsWe performed acute experiments during scheduled surgeries of the upper limb with eligible subjects. We scanned a set of multicontact neural stimulation cuff electrode configurations, pre-computed through modeling simulations. We reported the obtained isolated and functional movements that were considered useful for the subject (different grasping movements).ResultsIn eight subjects, we demonstrated that selective stimulation based on multicontact cuff electrodes and optimized current spreading over the active contacts provided isolated, compound, functional and strong movements; most importantly 3 out of 4 had isolated fingers or thumb flexion, one patient performed a Key Grip, another one the Power and Hook Grips, and the 2 last all the 3 Grips. Several configurations were needed to target different areas within the nerve to obtain all the envisioned movements. We further confirmed that the upper limb nerves have muscle specific fascicles, which makes it possible to activate isolated movements.ConclusionsThe future goal is to provide patients with functional restoration of object grasping and releasing with a minimally invasive solution: only two cuff electrodes above the elbow.Ethics Committee / ANSM clearance prior to the beginning of the study (inclusion period 2016–2018): CPP Sud Méditerranée, #ID-RCB:2014-A01752–45, first acceptance 10th of February 2015, amended 12th of January 2016.Trial registration(www.clinicaltrials.gov): #NCT03721861, Retrospectively registered on 26th of October 2018.

Sensory neuroprosthesis improves postural stability during Sensory Organization Test in lower-limb amputees

To maintain postural stability, unilateral lower-limb amputees (LLAs) heavily rely on visual and vestibular inputs, and somatosensory cues from their intact leg to compensate for missing somatosensory information from the amputated limb. When any of these resources are compromised, LLAs exhibit poor balance control compared to able-bodied individuals. We hypothesized that restoring somatosensation related to the missing limb via direct activation of the sensory nerves in the residuum would improve the standing stability of LLAs. We developed a closed-loop sensory neuroprosthesis utilizing non-penetrating multi-contact cuff electrodes implanted around the residual nerves to elicit perceptions of the location and intensity of plantar pressures under the prosthetic feet of two transtibial amputees. Effects of the sensory neuroprosthesis on balance were quantified with the Sensory Organization Test and other posturographic measures of sway. In both participants, the sensory neuroprosthesis improved equilibrium and sway when somatosensation from the intact leg and visual inputs were perturbed simultaneously. One participant also showed improvement with the sensory neuroprosthesis whenever somatosensation in the intact leg was compromised via perturbations of the platform. These observations suggest the sensory feedback elicited by neural stimulation can significantly improve the standing stability of LLAs, particularly when other sensory inputs are depleted or otherwise compromised.

Model based optimal multipolar stimulation without a priori knowledge of nerve structure: application to vagus nerve stimulation

Objective. Multipolar cuff electrode can selectively stimulate areas of peripheral nerves and therefore enable to control independent functions. However, the branching and fascicularization are known for a limited set of nerves and the specific organization remains subject-dependent. This paper presents general modeling and optimization methods in the context of multipolar stimulation using a cuff electrode without a priori knowledge of the nerve structure. Vagus nerve stimulation experiments based on the optimization results were then investigated. Approach. The model consisted of two independent components: a lead field matrix representing the transfer function from the applied current to the extracellular voltage present on the nodes of Ranvier along each axon, and a linear activation model. The optimization process consisted in finding the best current repartition (ratios) to reach activation of a targeted area depending on three criteria: selectivity, efficiency and robustness. Main results. The results showed that state-of-the-art configurations (tripolar transverse, tripolar longitudinal) were part of the optimized solutions but new ones could emerge depending on the trade-off between the three criteria and the targeted area. Besides, the choice of appropriate current ratios was more important than the choice of the stimulation amplitude for a stimulation without a priori knowledge of the nerve structure. We successfully assessed the solutions in vivo to selectively induce a decrease in cardiac rhythm through vagus nerve stimulation while limiting side effects. Compared to the standard whole ring configuration, a selective solution found by simulation provided on average 2.6 less adverse effects. Significance. The preliminary results showed the rightness of the simulation, using a generic nerve geometry. It suggested that this approach will have broader applications that would benefit from multicontact cuff electrodes to elicit selective responses. In the context of the vagus nerve stimulation for heart failure therapy, we show that the simulation results were confirmed and improved the therapy while decreasing the side effects.

Assessment on selectivity of multi-contact cuff electrode for recording peripheral nerve signals using Fitzhugh-Nagumo model of nerve excitation.

Nerve cuff electrodes provide a safe technique for recording nerve signals. Defining a more realized modeling to investigate the selectivity of a cuff electrode in recording from peripheral nervous system is an interesting field of research. A four-contact cuff electrode was modeled to evaluate selective recording from a peripheral nerve. Fitzhugh-Nagumo equations were used to model the electromagnetic fields generated by active nerves and electrodes and the ``selectivity index'' used to quantify the selective property of the cuff electrode. The action potentials amplitude and impulse velocity generated by Fitzhugh-Nagumo model are similar to real-life nerve measurements according to the literature. The electrical field distribution caused by the impulse propagation along a specific nerve was the maximum near the corresponding contact. Also, the selectivity was increased with increasing the distance between the active sources and the number of contacts. The results of this research showed that Fitzhugh-Nagumo equations could model the nerve excitation accurately and could be used in computer simulation for studying nervous systems. Also, using these equations indicated that multi-contact cuff electrodes could be used in recording peripheral nerve signals in order to discriminate active fascicles in a nerve bundle.

Functional monitoring of peripheral nerves from electrical impedance measurements

Medical electrical stimulators adapted to peripheral nerves use multicontact cuff electrodes (MCC) to provide selective neural interfaces. However, neuroprostheses are currently limited by their inability to locate the regions of interest to focus. Intended until now either for stimulation or recording, MCC can also be used as a means of transduction to characterize the nerve by impedancemetry. In this study, we investigate the feasibility of using electrical impedance (EI) measurements as an in vivo functional nerve monitoring technique. The monitoring paradigm includes the synchronized recording of both the evoked endogenous activity as compound action potentials (CAP) and the superimposed sine signal from the EI probe. Measurements were conducted on the sciatic nerve of rodents, chosen for its branchings towards the peroneal and tibial nerves, with both mono- and multi-contact per section electrodes. During stimulation phases, recordings showed CAP with consistent fiber conduction velocities. During coupled phases of both stimulation and sine perturbation, impedance variations were extracted using the mono-contact electrode type for certain frequencies, e.g. 2.941kHz, and were temporally coherent with the previous recorded CAP. Using a MCC, localized evoked CAP were also recorded but the signal to noise ratio (SNR) was too low to distinguish the expected associated impedance variation and deduce an image of impedance spatial changes within the nerve. The conducted in vivo measurements allowed to distinguish both evoked CAP and associated impedance variations with a strong temporal correlation. This indicates the feasibility of functional EI monitoring, aiming at detecting the impedance variations in relation to neural activity. Further work is needed to improve the in vivo system, namely in terms of SNR, and to integrate new multicontact devices in order to move towards EI tomography with the detection of spatially-localized impedance variations. Eventually, regions that are interesting to be targeted by stimulation could be identified through these means.

Fast Simulation and Optimization Tool to Explore Selective Neural Stimulation.

In functional electrical stimulation, selective stimulation of axons is desirable to activate a specific target, in particular muscular function. This implies to simulate a fascicule without activating neighboring ones i.e. to be spatially selective. Spatial selectivity is achieved by the use of multicontact cuff electrodes over which the stimulation current is distributed. Because of the large number of parameters involved, numerical simulations provide a way to find and optimize electrode configuration. The present work offers a computation effective scheme and associated tool chain capable of simulating electrode-nerve interface and find the best spread of current to achieve spatial selectivity.

Effect of contacts configuration and location on selective stimulation of cuff electrode.

Cuff electrodes have been widely used chronically in different clinical applications. Advancements have been made in selective stimulation by using multi-contact cuff electrodes. Steering anodic current is a strategy to increase selectivity by reshaping and localizing electric fields. There are two configurations for contacts to be implemented in cuff, monopolar and tripolar. A cuff electrode with tripolar configuration can restrict the activation to a more localized region within a nerve trunk compared to a cuff with monopolar configuration and improve the selectivity. Anode contacts in tripolar configuration can be made in two structures, "ring" and "dot". In this study, the stimulation capabilities of these two structures were evaluated. The recruitment properties and the selectivity of stimulation were examined by measuring the electric potential produced by stimulation currents. The results of the present study indicated that using dot configuration, the current needed to stimulate fascicles in tripolar topologies would be reduced by 10%. It was also shown that stimulation threshold was increased by moving anode contacts inward the cuff. On the other hand, stimulation threshold was decreased by moving the anode contacts outward the cuff which would decrease selectivity, too. We conclude that dot configuration is a better choice for stimulation. Also, a cuff inward placement of 10% relative to the cuff length was near optimal.

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.

Targeted Hypoglossal Neurostimulation in Obstructive Sleep Apnea

Objective: Airway management is the standard approach for the treatment of obstructive sleep apnea (OSA). CPAP remains the gold standard to treat OSAS, but about one-quarter of the patients are poorly compliant or tolerant to the mask. The aim of the study was to evaluate the safety and efficacy of targetted neurostimulation of the hypoglossal nerve (THN Sleep Therapy) in CPAP non-compliant subjects using the aura6000™ System from ImThera Medical Inc. Method: The study was a single arm, prospective feasibility study on 13 OSA subjects. Apnea-hypopnea indices (AHI) were measured at 3 and 12 months. A multi-contact cuff electrode was implanted unilaterally on the proximal hypoglossal nerve and an implantable pulse generator placed subcutaneously in the ipsilateral upper chest wall. Results: Significant improvement was found in the apnea hypopnea index: baseline 45.2 ± 17.8, 3 months 21.7 ± 19.9, and 12 months 21.0 ± 16.5 calculated for the 13 patients. Ten patients were classified as responders (76.92%) with a 65.55% improvement in the AHI at 3 months and 68.19% at 12 months and with a 67.09% improvement in the ODI at 3 months and 66.23% at 12 months. Conclusion: THN Sleep Therapy™ proved to be a feasible and effective procedure for the treatment of the moderate to severe CPAP noncompliant OSA subjects.

Experimental validation of the nerve conduction velocity selective recording technique using a multi-contact cuff electrode

The earthworm ( Lumbricus terrestris) is presented as an in vitro model of a peripheral nerve containing only two fibers each with distinctly different conduction velocities, the median and lateral giant fibers (MGF and LGF). The worm model is used with a multi-contact cuff electrode to validate the spatial–temporal filtering effect of different electrode contact configurations and the effect of applying a delay adder and matched filter tuned to either the MGF or LGF action potential (AP) to extract conduction direction and velocity from the recording. The results confirmed the known effect of inter-electrode spacing and bipolar and tripolar recording configuration on the AP amplitude. It also demonstrates a crossover point where the amplitude of the tripolar recording is larger than the monopolar recording, an effect of the slower action potential conduction velocities in the worm. The delay adder was found to be an effective velocity sensitive filter, able to discriminate units based on conduction velocity. The matched filter to be an effective means to eliminate artifact and increase signal to noise ratios, however was not found to improve selectivity.

Localization of Active Pathways in Peripheral Nerves: A Simulation Study

A methodology is investigated for determining the location of active pathways in a peripheral nerve using measurements from a multicontact cuff electrode. The problem is treated as an inverse problem of source localization and solved using the sLORETA algorithm, developed for the electroencephalogram/magnetoencephalogram source localization problem. Simulated measurements are generated corresponding to action potentials traveling along either one or three pathways in a rat sciatic nerve. The performance of the proposed methodology using these measurements is evaluated in terms of localization error, missed pathways, and spurious pathways. The source localization performance when assuming an idealized nerve anatomy is compared to that when the correct anatomy is known. The effect of a spatio-temporal constraint based on the nerve anatomy and electrophysiology is also investigated. The approach in its present form was not found to be sufficiently reliable for subfascicular localization in practice, due to mean localization errors in the 140-180 mum range, high numbers of spurious pathways, and low resolution. Nonetheless, the constraints were shown to produce a marked reduction in the number of spurious pathways. Conditions under which the source localization approach may be useful for peripheral nerves are discussed.

Nerve Stimulation With A Multi-Contact Cuff Electrode: Validation Of Model Predictions

The recruitment characteristics of muscle selective nerve stimulation by a multi-contact nerve cuff electrode, as predicted by computer modeling, have been investigated in acute experiments on rabbits. A nerve cuff containing five or six dot electrodes was placed around the sciatic nerve in five rabbits. M-waves were recorded with wire electrodes from the lateral gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. The muscle recruitment performances of three contact configurations (monopole, transverse bipole, transverse tripole) were compared. The selectivity was quantified by the recruitment of two muscles (one extensor and one flexor) in response to a particular stimulus. The results showed that only in a few cases, transverse bi- and tripolar stimulation provided a better selectivity than monopolar stimulation. Neither of the two extensors, nor of the two flexors could be stimulated separately. In accordance with the results of the modeling studies, bi- and tripolar stimulation required higher stimulus currents than monopolar stimulation, whereas maximum recruitment and slopes of recruitment curves were lower. The rabbit sciatic nerve appears to be a less suitable preparation for reproducible selectivity experiments, due to the variability in the number and size of the fascicles and their position in this nerve.