Transverse Intrafascicular Multichannel Electrode Research Articles

Restoration of coherent reach-grasp-pull movement via sequential intraneural peripheral nerve stimulation in rats

Objective. Peripheral nerve stimulation (PNS) has been demonstrated as an effective way to selectively activate muscles and to produce fine hand movements. However, sequential multi-joint upper limb movements, which are critical for paralysis rehabilitation, has not been tested with PNS. Here, we aimed to restore multiple upper limb joint movements through an intraneural interface with a single electrode, achieving coherent reach-grasp-pull movement tasks through sequential stimulation. Approach. A transverse intrafascicular multichannel electrode was implanted under the axilla of the rat’s upper limb, traversing the musculocutaneous, radial, median, and ulnar nerves. Intramuscular electrodes were implanted into the biceps brachii (BB), triceps brachii (TB), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles to record electromyographic (EMG) activity and video recordings were used to capture the kinematics of elbow, wrist, and digit joints. Charge-balanced biphasic pulses were applied to different channels to recruit distinct upper limb muscles, with concurrent recording of EMG signals and joint kinematics to assess the efficacy of the stimulation. Finally, a sequential stimulation protocol was employed by generating coordinated pulses in different channels. Main results. BB, TB, FCR and ECR muscles were selectively activated and various upper limb movements, including elbow flexion, elbow extension, wrist flexion, wrist extension, digit flexion, and digit extension, were reliably generated. The modulation effects of stimulation parameters, including pulse width, amplitude, and frequency, on induced joint movements were investigated and reach-grasp-pull movement was elicited by sequential stimulation. Significance. Our results demonstrated the feasibility of sequential intraneural stimulation for functional multi-joint movement restoration, providing a new approach for clinical rehabilitation in paralyzed patients.

Bringing sensation to prosthetic hands—chronic assessment of implanted thin-film electrodes in humans

Direct stimulation of peripheral nerves with implantable electrodes successfully provided sensory feedback to amputees while using hand prostheses. Longevity of the electrodes is key to success, which we have improved for the polyimide-based transverse intrafascicular multichannel electrode (TIME). The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months. We present a comprehensive assessment of the electrical properties of the thin-film metallization as well as material status post explantationem. The TIMEs stayed within the electrochemical safe limits while enabling consistent and precise amplitude modulation. This lead to a reliable performance in terms of eliciting sensation. No signs of corrosion or morphological change to the thin-film metallization of the probes was observed by means of electrochemical and optical analysis. The presented longevity demonstrates that thin-film electrodes are applicable in permanent implant systems.

Modulating individual axons and axonal populations in the peripheral nerve using transverse intrafascicular multichannel electrodes.

Objective.A transverse intrafascicular multichannel electrode (TIME) may offer advantages over more conventional cuff electrodes including higher spatial selectivity and reduced stimulation charge requirements. However, the performance of TIME, especially in the context of non-conventional stimulation waveforms, remains relatively unexplored. As part of our overarching goal of investigating stimulation efficacy of TIME, we developed a computational toolkit that automates the creation and usage ofin siliconerve models with TIME setup, which solves nerve responses using cable equations and computes extracellular potentials using finite element method.Approach.We began by implementing a flexible and scalable Python/MATLAB-based toolkit for automatically creating models of nerve stimulation in the hybrid NEURON/COMSOL ecosystems. We then developed a sciatic nerve model containing 14 fascicles with 1,170 myelinated (A-type, 30%) and unmyelinated (C-type, 70%) fibers to study fiber responses over a variety of TIME arrangements (monopolar and hexapolar) and stimulation waveforms (kilohertz stimulation and cathodic ramp modulation).Main results.Our toolkit obviates the conventional need to re-create the same nerve in two disparate modeling environments and automates bi-directional transfer of results. Our population-based simulations suggested that kilohertz stimuli provide selective activation of targeted C fibers near the stimulating electrodes but also tended to activate non-targeted A fibers further away. However, C fiber selectivity can be enhanced by hexapolar TIME arrangements that confined the spatial extent of electrical stimuli. Improved upon prior findings, we devised a high-frequency waveform that incorporates cathodic DC ramp to completely remove undesirable onset responses.Conclusion.Our toolkit allows agile, iterative design cycles involving the nerve and TIME, while minimizing the potential operator errors during complex simulation. The nerve model created by our toolkit allowed us to study and optimize the design of next-generation intrafascicular implants for improved spatial and fiber-type selectivity.

Combining biophysical models and machine learning to optimize implant geometry and stimulation protocol for intraneural electrodes

Objective. Peripheral nerve interfaces have the potential to restore sensory, motor, and visceral functions. In particular, intraneural interfaces allow targeting deep neural structures with high selectivity, even if their performance strongly depends upon the implantation procedure and the subject’s anatomy. Currently, few alternatives exist for the determination of the target subject structural and functional anatomy, and statistical characterizations from cadaveric samples are limited because of their high cost. We propose an optimization workflow that can guide both the pre-surgical planning and the determination of maximally selective multisite stimulation protocols for implants consisting of several intraneural electrodes, and we characterize its performance in silico. We show that the availability of structural and functional information leads to very high performances and allows taking informed decisions on neuroprosthetic design. Approach. We employ hybrid models (HMs) of neuromodulation in conjunction with a machine learning-based surrogate model to determine fiber activation under electrical stimulation, and two steps of optimization through particle swarm optimization to optimize in silico implant geometry, implantation and stimulation protocols using morphological data from the human median nerve at a reduced computational cost. Main results. Our method allows establishing the optimal geometry of multi-electrode transverse intra-fascicular multichannel electrode implants, the optimal number of electrodes to implant, their optimal insertion, and a set of multipolar stimulation protocols that lead in silico to selective activation of all the muscles innervated by the human median nerve. Significance. We show how to use effectively HMs for optimizing personalized neuroprostheses for motor function restoration. We provide in-silico evidences about the potential of multipolar stimulation to increase greatly selectivity. We also show that the knowledge of structural and functional anatomies of the target subject leads to very high selectivity and motivate the development of methods for their in vivo characterization.

New Stimulation Device to Drive Multiple Transverse Intrafascicular Electrodes and Achieve Highly Selective and Rich Neural Responses.

Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator—called STIMEP—and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes.

Computational approaches to decode grasping force and velocity level in upper-limb amputee from intraneural peripheral signals

Objective. Recent results have shown the potentials of neural interfaces to provide sensory feedback to subjects with limb amputation increasing prosthesis usability. However, their advantages for decoding motor control signals over current methods based on electromyography (EMG) are still debated. In this study we compared a standard EMG-based method with approaches that use peripheral intraneural data to infer distinct levels of grasping force and velocity in a trans-radial amputee. Approach. Surface EMG (three channels) and intraneural signals (collected with transverse intrafascicular multichannel electrodes, TIMEs, 56 channels) were simultaneously recorded during the amputee’s intended grasping movements. We sorted single unit activity (SUA) from each neural signal and then we identified the most informative units. EMG envelopes were extracted from the recorded EMG signals. A reference support vector machine (SVM) classifier was used to map EMG envelopes into desired force and velocity levels. Two decoding approaches using SUA were then tested and compared to the EMG-based reference classifier: (a) SVM classification of firing rates into desired force and velocity levels; (b) reconstruction of covariates (the grasp cue level or EMG envelopes) from neural data and use of covariates for classification into desired force and velocity levels. Main results. Using EMG envelopes as reconstructed covariates from SUA yielded significantly better results than the other approaches tested, with performance similar to that of the EMG-based reference classifier, and stable over three different recording days. Of the two reconstruction algorithms used in this approach, a linear Kalman filter and a nonlinear point process adaptive filter, the nonlinear filter gave better results. Significance. This study presented a new effective approach for decoding grasping force and velocity from peripheral intraneural signals in a trans-radial amputee, which relies on using SUA to reconstruct EMG envelopes. Being dependent on EMG recordings only for the training phase, this approach can fully exploit the advantages of implanted neural interfaces and potentially overcome, in the medium to long term, current state-of-the-art methods. (Clinical trial’s registration number: NCT02848846).

Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance

Objective. Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. Approach. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d. Main results. About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Significance. Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications. (Document number of Ethical Committee: P/905/CE/2012; Date of approval: 2012–10-04)

Decoding of grasping tasks from intraneural recordings in trans-radial amputee

Objective. A major challenge in neuroprosthetics is the restoration of sensory-motor hand functions in upper-limb amputees. Neuroprostheses based on the direct re-connection of the peripheral nerves may be an interesting approach for re-establishing the natural and effective bidirectional control of hand prostheses. Recent results have shown that transverse intrafascicular multi-channel electrodes (TIMEs) can restore natural and sophisticated sensory feedback. However, the potential of using TIME-recorded motor intraneural signals to decode grasping tasks has not as yet been explored. Approach. In this study, we show that several hand-movement intentions can be decoded from intraneural signals recorded using four TIMEs implanted in the median and ulnar nerves of an upper limb amputee. Experimental sessions were performed over a week, from day 16 to day 23 after the surgical operation. Intraneural activity was recorded during several hand motor tasks imagined by the subject and processed offline. Main results. We obtained a very high decoding accuracy considering 11 class states (up to 83%). These results confirm that neural signals recorded by multi-channel intraneural electrodes can be used to decode several movement intentions with high accuracy. Moreover, we were able to use same TIME channels for decoding over one week within the first month, even if the stability has to be confirmed during long-term experiments. Significance. Therefore, TIMEs could be used in the future to achieve a complete bidirectional approach exploiting neural pathways, to make a more natural and intuitive new generation of hand prostheses that have a closer resemblance to a healthy hand.

Characterization of multi-channel intraneural stimulation in transradial amputees

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.

Micro-channel sieve electrode for concurrent bidirectional peripheral nerve interface. Part A: recording

Objective. Advancement in prosthetic limb technology requires corresponding improvements in the capability of the amputee to naturally control the device via original motor pathways while simultaneously receiving haptic feedback via sensory pathways. Recording efferent axonal activity using a peripheral neural interface (PNI) allows a good tradeoff between invasiveness and selectivity while possibly preserving the phenomenology of controlling the original limb. One such PNI, the thin-film transverse intrafascicular multichannel electrode (tfTIME), has been shown to be successful in controlling powered prosthetics. However, the tfTIME is highly susceptible to stimulation artifact; thus, using such a PNI to both record efferent motor signals while concurrently stimulating afferent sensory axons in the same nerve is problematic. The micro-channel sieve electrode could also provide a stable, selective, neural interface with larger signal-to-noise levels that are less susceptible to concurrent stimulation artifact or other external noise effects. Approach. This study uses a computational model to compare recording levels of simulated ENGs across neural drive levels as well as basic control signals derived from the ENGs in both tfTIME and micro-channel sieve PNIs. A motor neuron pool model generated axon firing rates at a given neural drive. The time course of the corresponding extracellular currents of the myelinated motor axons were determined using core conductor axon models. Finite element models determined the contribution of the extracellular current from nodes of Ranvier on potentials recorded using each interface. Contributions from each node were combined to create the final ENG. Main results. ENGs recorded using the micro-channel sieves were shown to have much higher amplitudes compared to ENGs recorded using the tfTIMEs. Signal amplitudes also varied less as a function of axonal placement and spike timing, resulting in more consistent signals with amplitudes determined predominantly by neural drive. Significance. Simulation results suggest that the micro-channel sieve provides higher quality control signals over tfTIME PNIs in decoding ENGs. Coupling these results with concurrent stimulation results of the companion paper (Part B: stimulation) suggests that the micro-channel sieve is an optimal bidirectional PNI.

Micro-channel sieve electrode for concurrent bidirectional peripheral nerve interface. Part B: stimulation

Objective. Successful use of a prosthetic limb by an amputee is facilitated by haptic feedback—both a sense of touch and proprioception. Stimulating afferent fibers within peripheral nerves has been shown to provide somatosensation enabling amputees to modulate the control of prosthetic limbs. Peripheral nerve interfaces (PNIs) have also been used to decode patients’ motor intentions. It seems ideal to use PNIs to record efferent fibers for motor control while stimulating afferent fibers to create concurrent sensory feedback. However, while many PNIs claim to be bi-directional, few can both stimulate and record at the same time due to stimulation artifacts which are orders of magnitude larger than the recorded motor signals. This study uses computational modelling to compare the stimulation artifact at threshold levels of stimulation for thin-film transverse intrafascicular multichannel electrodes (tfTIMEs) with micro-channel sieve electrodes. Approach. Finite element models of micro-channel sieves and tfTIMESs were used to solve for electric fields generated during peripheral nerve stimulation. Electrophysiological responses were simulated using axon models. Stimulation artifacts were calculated for stimuli eliciting axonal action potentials. Simulations were carried out for multiple micro-channel geometries and electrode configurations. Main results. Stimulation artifacts generated for threshold stimulation currents are lower for micro-channel devices compared to tfTIMEs. Consequently, stimulus artifacts at threshold currents were substantially higher for the tfTIME. Micro-channel width has a moderate impact on recruitment thresholds and stimulus artifacts. Using the micro-channel sieve in bipolar and tripolar stimulation configurations greatly decreases stimulation artifacts particularly for optimized contact placements (CPs). Electroneurogram (ENG) signals from the companion paper were incorporated showing a great improvement in signal-to-artifact ratio for the micro-channel electrode compared to tfTIMEs. Significance. Stimulating regenerated nerve tissue using micro-channel sieve electrodes can decrease stimulation artifacts and elicit neuronal responses at low stimulation amplitudes. Further analysis provides clues to optimal implementations of micro-channel devices. Finally, stimulation artifacts for simulated tfTIME devices were 2–3 orders of magnitude larger than ENG levels. In contrast, for some micro-channel configurations stimulation artifacts were 3–4 orders of magnitude smaller than ENG levels.

Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback.

Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated. To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks. All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state. The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154.

Design and assessment of stimulation parameters for a novel peripheral nerve interface.

Bi-directional interfaces for peripheral nerve stimulation and recording aim to improve control and acceptance of sensorized prosthetic limbs. The implantable multimodal peripheral recording and stimulation system (IMPRESS) is an intraneural interface technology supporting a high-density transverse intrafascicular multichannel electrode (hd-TIME). Herein we report on in vivo selectivity studies using a passive hd-TIME, and computational modeling towards optimal stimulation parameters for fiber recruitment.

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.

T156. Restoration of somatosensory feedback and bidirectional real-time control of a prosthetic hand using peripheral nervous system signals

Hand amputation is a highly disabling event, which significantly affects quality of life. Effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the rich sensations that are naturally perceived while grasping and moving. We already demonstrated with promising results the possibility to restore, for a short period of 30 days, the somatosensory feedback from the lost hand in an amputee by implanting four transverse intrafascicular multichannel electrodes (TIMEs) into the residual nerves of the stump. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated. To this aim, we performed a six-month clinical study with two trans-radial amputees who received implants of four TIMEs in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks. The subjects reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests resembling realistic tasks (with and without the support of vision).The results also demonstrate that a high complexity of perception can be obtained, allowing the subjects to identify the stiffness and shape of different objects. The results achieved with the two subjects show the feasibility of longterm use of intraneural stimulation and improve the knowledge about the new type of bidirectional hand prostheses, for a more near-natural replacement as possible of missing hands.

Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees

ObjectiveThe aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording “phantom” somatosensory evoked potentials from the corresponding brain areas. MethodsWe implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials. ResultsWe recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex. ConclusionOur results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses. SignificanceSomatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses.

Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves.

Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME.

The number of devices for electrical stimulation of nerve fibres implanted worldwide for medical applications is constantly increasing. Stimulation charge is one of the most important parameters of stimulation. High stimulation charge may cause tissue and electrode damage and also compromise the battery life of the electrical stimulators. Therefore, the objective of minimizing stimulation charge is an important issue. Delaying the second phase of biphasic stimulation waveform may decrease the charge required for fibre activation, but its impact on stimulation selectivity is not known. This information is particularly relevant when transverse intrafascicular multichannel electrode (TIME) is used, since it has been designed to provide for high selectivity. In this in vivo study, the rat sciatic nerve was electrically stimulated using monopolar and bipolar configurations with TIME. The results demonstrated that the inclusion of a 100-μs delay between the cathodic and the anodic phase of the stimulus allows to reduce charge requirements by around 30%, while only slightly affecting stimulation selectivity. This study shows that adding a delay to the typical stimulation waveform significantly ([Formula: see text]) reduces the charge required for nerve fibres activation. Therefore, waveforms with the delayed discharge phase are more suitable for electrical stimulation of nerve fibres.

Subchronic stimulation performance of transverse intrafascicular multichannel electrodes in the median nerve of the Göttingen minipig.

This work evaluated the subchronic stimulation performance of an intraneural multichannel electrode (transverse intrafascicular multichannel electrode, TIME) in a large human-sized nerve. One or two TIMEs were implanted in the right median nerve above the elbow joint in four pigs for a period of 32 to 37 days (six TIMEs in total). The ability of the contact sites to recruit five muscles in the forelimb was assessed via their evoked electromyographic responses. Based on these responses, a selectivity index was defined. Four TIMEs were able to selectively recruit a subset of muscles throughout the implantation period. The required recruitment current significantly increased, while there was a tendency for the recruitment selectivity to decrease over time. Histological assessment showed that all TIMEs remained inside the nerve and that they were located between fascicles. The average thickness of the encapsulation of the electrode was estimated to be 115.4 ± 51.5 μm (mean ± SD). This study demonstrates the feasibility of keeping the TIME electrodes fixed and functional inside a large polyfascicular human-sized nerve in a subchronic setting.

Biosafety assessment of an intra-neural electrode (TIME) following sub-chronic implantation in the median nerve of Göttingen minipigs.

Before a novel peripheral nerve interface can be applied in a neural prosthesis for human use, it is important to determine the biocompatibility of the device. The aim of the present study was to assess the biosafety of the recently developed transverse intrafascicular multi-channel electrode (TIME) in a large nerve animal model. Six TIMEs were implanted (33-38 days) into the median nerves of Göttingen minipigs, and nerve specimens were harvested for histological analysis. We analyzed samples from the area of the implant and from control regions. We found an expected layer of fibrosis around the implant and fibroblasts in both the implant and control region, however, we found no significant presence of inflammatory cells or necrosis. Our results indicated that the TIME may be an attractive, biocompatible neural interface for future neuroprosthesis applications in the clinic setting.