Multi-electrode Cuff Research Articles

Stimulation parameters for directional vagus nerve stimulation

BackgroundAutonomic nerve stimulation is used as a treatment for a growing number of diseases. We have previously demonstrated that application of efferent vagus nerve stimulation (eVNS) has promising glucose lowering effects in a rat model of type 2 diabetes. This paradigm combines high frequency pulsatile stimulation to block nerve activation in the afferent direction with low frequency stimulation to activate the efferent nerve section. In this study we explored the effects of the parameters for nerve blocking on the ability to inhibit nerve activation in the afferent direction. The overarching aim is to establish a blocking stimulation strategy that could be applied using commercially available implantable pulse generators used in the clinic.MethodsMale rats (n = 20) had the anterior abdominal vagus nerve implanted with a multi-electrode cuff. Evoked compound action potentials (ECAP) were recorded at the proximal end of the electrode cuff. The efficacy of high frequency stimulation to block the afferent ECAP was assessed by changes in the threshold and saturation level of the response. Blocking frequency and duty cycle of the blocking pulses were varied while maintaining a constant 4 mA current amplitude.ResultsDuring application of blocking at lower frequencies (≤ 4 kHz), the ECAP threshold increased (ANOVA, p < 0.001) and saturation level decreased (p < 0.001). Application of higher duty cycles (> 70%) led to an increase in evoked neural response threshold (p < 0.001) and a decrease in saturation level (p < 0.001). During the application of a constant pulse width and frequency (1 or 1.6 kHz, > 70% duty cycle), the charge delivered per pulse had a significant influence on the magnitude of the block (ANOVA, p = 0.003), and was focal (< 2 mm range).ConclusionsThis study has determined the range of frequencies, duty cycles and currents of high frequency stimulation that generate an efficacious, focal axonal block of a predominantly C-fiber tract. These findings could have potential application for the treatment of type 2 diabetes.

Artificial TMAP Signal Generator Based on One-Bit Sigma Delta Modulator for MEC Test

The current study proposes three electrode-channels with time delay of artificial nerve signals generator utilized with only a active low pass filter and a Field Programmable Gate Array (FPGA). The XC3S100E FPGA board adopted to design a novel and real-time artificial transmembrane action potential (TMAP). The implementation of one bit Sigma Delta Modulation (SDM) method with linearized technique could be very expensive and complicated products with other technologies option currently available such as a microcontroller due to the fabrication requirements. This technique could employ in many biomedical applications and testing efficiently, especially, in evaluating the multi-electrode cuff system without requiring use of real nerves spike from animal models and saving time and effort, and cost. Moreover, this approach is adopted for further improvement to the signal performances such as resolution, accuracy, differential linearity monotonic DAC, and settling time of the signal waveform without extra hardware or cost required. In addition, the design included three channels of white Gaussian noise uncorrelated for each TMAP signal to simulate the real nerve noise environment, which surrounds the electrode cuff in experimental cases. A noise channels with adjustment level is added to the nerve spike using three sets of taps are employed to provide three channels of noise sources. The Xilinx ISE platform and Mentor Graphics ModelSim tool are used to simulate and implement this, and the results produced are compared. The power consumption of conventional technology is 31 mW, which is significantly higher than the power consumed (21mW) in modern technology. Furthermore, as compared to the usual way, the proposed solution conserved around 10% of the FPGA resources. This technique offers reuse in other applications where delay time, low amplitude voltage signals, and multichannel generator is needed. Moreover, this system offers adjustable waveform signal, noise level, conduction velocity and time delay easily to adequate different applications and tests.

A Soft and Stretchable Multielectrode Cuff for Selective Peripheral Nerve Stimulation

AbstractBioelectronic medicine can treat diseases and disorders in humans by electrically interfacing with peripheral nerves. Multielectrode cuffs can be used for selective stimulation of portions of the nerve, which is advantageous for treatment specificity. The biocompatibility and conformability of cuffs can be improved by reducing the mechanical mismatch between nerve tissue and cuffs, but selective stimulation of nerves has yet to be achieved with soft and stretchable cuff electrodes. Here, this paper reports the development of a soft and stretchable multielectrode cuff (sMEC) for selective nerve stimulation. The device is made of 50 µm thick silicone with embedded gold nanowire conductors, which renders it functional at 50% strain, and provides superior conformability for wrapping nerves. By using different stimulation protocols, high functional selectivity is achieved with the sMEC's eight stimulation electrodes in a porcine sciatic nerve model. Finite element modeling is used to predict the potential distribution within the nerve, which correlate well with the achieved stimulation results. Recent studies are showing that mechanical softness is of outermost importance for reducing foreign body response. It is therefore believed that the soft high‐performance sMEC technology is ideal for future selective peripheral nerve interfaces for bioelectronic medicine.

The Use of the Velocity Selective Recording Technique to Reveal the Excitation Properties of the Ulnar Nerve in Pigs.

Decoding information from the peripheral nervous system via implantable neural interfaces remains a significant challenge, considerably limiting the advancement of neuromodulation and neuroprosthetic devices. The velocity selective recording (VSR) technique has been proposed to improve the classification of neural traffic by combining temporal and spatial information through a multi-electrode cuff (MEC). Therefore, this study investigates the feasibility of using the VSR technique to characterise fibre type based on the electrically evoked compound action potentials (eCAP) propagating along the ulnar nerve of pigs in vivo. A range of electrical stimulation parameters (amplitudes of 50 μA–10 mA and pulse durations of 100 μs, 500 μs, 1000 μs, and 5000 μs) was applied on a cutaneous and a motor branch of the ulnar nerve in nine Danish landrace pigs. Recordings were made with a 14 ring MEC and a delay-and-add algorithm was used to convert the eCAPs into the velocity domain. The results revealed two fibre populations propagating along the cutaneous branch of the ulnar nerve, with mean velocities of 55 m/s and 21 m/s, while only one dominant fibre population was found for the motor branch, with a mean velocity of 63 m/s. Because of its simplicity to provide information on the fibre selectivity and direction of propagation of nerve fibres, VSR can be implemented to advance the performance of the bidirectional control of neural prostheses and bioelectronic medicine applications.

Epidural and transcutaneous spinal cord stimulation facilitates descending inputs to upper-limb motoneurons in monkeys

Objective. There is renewed interest in epidural and transcutaneous spinal cord stimulation (SCS) as a therapy following spinal cord injury, both to reanimate paralyzed muscles as well as to potentiate weakened volitional control of movements. However, most work to date has focussed on lumbar SCS for restoration of locomotor function. Therefore, we examined upper-limb muscle responses and modulation of supraspinal-evoked movements by different frequencies of cervical SCS delivered to various epidural and transcutaneous sites in anaesthetized, neurologically intact monkeys. Approach. Epidural SCS was delivered via a novel multielectrode cuff placed around both dorsal and ventral surfaces of the cervical spinal cord, while transcutaneous SCS was delivered using a high carrier frequency through surface electrodes. Main results. Ventral epidural SCS elicited robust movements at lower current intensities than dorsal sites, with evoked motor unit potentials that reliably followed even high-frequency trains. By contrast, the muscle responses to dorsal SCS required higher current intensities and were attenuated throughout the train. However, dorsal epidural SCS and, to a lesser extent, transcutaneous SCS were effective at facilitating supraspinal-evoked responses, especially at intermediate stimulation frequencies. The time- and frequency-dependence of dorsal SCS effects could be explained by a simple model in which transynaptic excitation of motoneurons was gated by prior stimuli through presynaptic mechanisms. Significance. Our results suggest that multicontact electrodes allowing access to both dorsal and ventral epidural sites may be beneficial for combined therapeutic purposes, and that the interaction of direct, synaptic and presynaptic effects should be considered when optimising SCS-assisted rehabilitation.

WITHDRAWN: Neural action potential detection based on an adaptive filter for neural recordings

Abstract Neural action potential recordings are applied widely in medical applications and research. The action potential detection approach is essential to evaluation the times at which spike activated. Recordings from the multi-electrode cuff typically have a minimum signal to noise ratio less than 10. In this paper, an LSM adaptive filter is designed and implemented employing Matlab and Xilinx Spartan 3E-100 (xc3s100e) software and hardware tool. The proposal filter shows a significant enhancement in the noise rejection and power-consuming and hardware size reduction. Furthermore, the outcomes illustrate that the LSM adaptive filter efficiently works in online neural recording with essential upgrading in the signal to noise ratio (SNR). Consequently, this improvement could lead to more spike detection accuracy. It can make the sensitivity of > 80% with a false positive rate of less than 6 Hz in recordings with SNR = 5, and it performs better than an optimal threshold detector using bandpass filter in recordings with SNR > 3. The present filter configuration offers a notable reduction of 10% in power consumption and 25% of the hardware required contrasting with the conventional approach of digital filter algorithm. Therefore, this study could suggest a crucial improvement to boost the neural recording to be applied as a control signal for the prosthetics devices.

Model-based geometrical optimisation and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation

BackgroundNeuromodulation by electrical stimulation of the human cervical vagus nerve may be limited by adverse side effects due to stimulation of off-target organs. It may be possible to overcome this by spatially selective stimulation of peripheral nerves. Preliminary studies have shown this is possible using a cylindrical multielectrode human-sized nerve cuff in vagus nerve selective neuromodulation. New methodThe model-based optimisation method for multi-electrode geometric design is presented. The method was applied for vagus nerve cuff array and suggested two rings of 14 electrodes, 3 mm apart, with 0.4 mm electrode width and separation and length 0.5−3 mm, with stimulation through a pair in the same radial position on the two rings. The electrodes were fabricated using PDMS-embedded stainless steel foil and PEDOT: pTS coating. ResultsIn the cervical vagus nerve in anaesthetised sheep, it was possible to selectively reduce the respiratory breath rate (RBR) by 85 ± 5% without affecting heart rate, or selectively reduce heart rate (HR) by 20 ± 7% without affecting respiratory rate. The cardiac- and pulmonary-specific sites on the nerve cross-sectional perimeter were localised with a radial separation of 105 ± 5 degrees (P < 0.01, N = 24 in 12 sheep). ConclusionsResults suggest organotopic or function-specific organisation of neural fibres in the cervical vagus nerve. The optimised electrode array demonstrated selective electrical neuromodulation without adverse side effects. It may be possible to translate this to improved treatment by electrical autonomic neuromodulation for currently intractable conditions.

Imaging fast neural traffic at fascicular level with electrical impedance tomography: proof of principle in rat sciatic nerve

Objective. Understanding the coding of neural activity in nerve fascicles is a high priority in computational neuroscience, electroceutical autonomic nerve stimulation and functional electrical stimulation for treatment of paraplegia. Unfortunately, it has been little studied as no technique has yet been available to permit imaging of neuronal depolarization within fascicles in peripheral nerve. Approach. We report a novel method for achieving this, using a flexible cylindrical multi-electrode cuff placed around nerve and the new medical imaging technique of fast neural electrical impedance tomography (EIT). In the rat sciatic nerve, it was possible to distinguish separate fascicles activated in response to direct electrical stimulation of the posterior tibial and common peroneal nerves. Main results. Reconstructed EIT images of fascicular activation corresponded with high spatial accuracy to the appropriate fascicles apparent in histology, as well as the inverse source analysis (ISA) of compound action potentials (CAP). With this method, a temporal resolution of 0.3 ms and spatial resolution of less than 100 µm was achieved. Significance. The method presented here is a potential solution for imaging activity within peripheral nerves with high spatial accuracy. It also provides a basis for imaging and selective neuromodulation to be incorporated in a single implantable non-penetrating peri-neural device.

An implantable ENG detector with in-system velocity selective recording (VSR) capability.

Detection and classification of electroneurogram (ENG) signals in the peripheral nervous system can be achieved by velocity selective recording (VSR) using multi-electrode arrays. This paper describes an implantable VSR-based ENG recording system representing a significant development in the field since it is the first system of its type that can record naturally evoked ENG and be interfaced wirelessly using a low data rate transcutaneous link. The system consists of two CMOS ASICs one of which is placed close to the multi-electrode cuff array (MEC), whilst the other is mounted close to the wireless link. The digital ASIC provides the signal processing required to detect selectively ENG signals based on velocity. The design makes use of an original architecture that is suitable for implantation and reduces the required data rate for transmission to units placed outside the body. Complete measured electrical data from samples of the ASICs are presented that show that the system has the capability to record signals of amplitude as low as 0.5μV, which is adequate for the recording of naturally evoked ENG. In addition, measurements of electrically evoked ENG from the explanted sciatic nerves of Xenopus Laevis frogs are presented.

Velocity Selective Neural Signal Recording Using a Space-Time Electrode Array.

Extracting the activity of a particular neural fiber from the extracellular recording of a peripheral nerve is quite important from different clinical perspectives. While traditional neural recording methods are unable to provide such granularity, new signal recording and processing techniques have offered promising solutions recently. A multi-electrode cuff in conjunction with a delay and sum beamforming structure has been used to detect the activity of different fibers in a nerve based on the propagation velocity of action potentials. However, as it is shown in this paper, simple delay and sum beamforming method encounters severe selectivity problem and signal distortion especially at higher velocities. In addition to scrutinizing the performance of the delay and sum beamformer and its inherent problems, here we propose a new beamforming method, based on broadband sensor array signal processing techniques, which exhibits much better selectivity with uniform frequency-velocity response. Our simulation results show how the new method can faithfully extract individual neural fiber activities and explore potential applications which could emerge from using such technique.

Fibre-selective recording from the peripheral nerves of frogs using a multi-electrode cuff**The work presented here was carried out at the laboratories of the Implanted Devices Group, Department of Medical Physics and Bioengineering, University College London, UK.

Objective. We investigate the ability of the method of velocity selective recording (VSR) to determine the fibre types that contribute to a compound action potential (CAP) propagating along a peripheral nerve. Real-time identification of the active fibre types by determining the direction of action potential propagation (afferent or efferent) and velocity might allow future neural prostheses to make better use of biological sensor signals and provide a new and simple tool for use in fundamental neuroscience. Approach. Fibre activity was recorded from explanted Xenopus Laevis frog sciatic nerve using a single multi-electrode cuff that records whole nerve activity with 11 equidistant ring-shaped electrodes. The recorded signals were amplified, delayed against each other with variable delay times, added and band-pass filtered. Finally, the resulting amplitudes were measured. Main Result. Our experiments showed that electrically evoked frog CAP was dominated by two fibre populations, propagating at around 20 and 40 m/s, respectively. The velocity selectivity, i.e. the ability of the system to discriminate between individual populations was increased by applying band-pass filtering. The method extracted an entire velocity spectrum from a 10 ms CAP recording sample in real time. Significance. Unlike the techniques introduced in the 1970s and subsequently, VSR requires only a single nerve cuff and does not require averaging to provide velocity spectral information. This makes it potentially suitable for the generation of highly-selective real-time control-signals for future neural prostheses. In our study, electrically evoked CAPs were analysed and it remains to be proven whether the method can reliably classify physiological nerve traffic.

The theory of velocity selective neural recording: a study based on simulation

This paper describes the improvements to the theory of velocity selective recording and some simulation results. In this method, activity in different groups of axons is discriminated by their propagation velocity. A multi-electrode cuff and an array of amplifiers produce multiple neural signals; if artificial delays are inserted and the signals are added, the activity in axons of the matched velocity are emphasized. We call this intrinsic velocity selective recording. However, simulation shows that interpreting the time signals is then not straight-forward and the selectivity Q(v) is low. New theory shows that bandpass filters improve the selectivity and explains why this is true in the time domain. A simulation study investigates the limits on the available velocity selectivity both with and without additive noise and with reasonable sampling rates and analogue-to-digital conversion parameters. Bandpass filters can improve the selectivity by factors up to 7 but this depends on the speed of the action potential and the signal-to-noise ratio.

Noise and selectivity of velocity-selective multi-electrode nerve cuffs

Using a multi-electrode nerve-signal recording cuff and a method of signal processing described previously, activity in axons with different propagation velocities can be distinguished, and the relative amplitude of the small-fibre signals increased. This paper is, largely, an analysis of the selectivity and noise of this system though impedance measurements from an actual cuff are included. The signal processor includes narrow band-pass filters. It is shown that the selectivity and noise both increase with the centre frequencies of these filters. A convenient approach is to make the filter frequencies inversely related to the artificial time delays so that the filter 'Q's are approximately constant and the noise densities are equal for all velocity filters. Numerical calculations, using formulae for this system and for the conventional tripole, based on a fixed cuff size and tissue resistivity, find the number of action potentials per second that must pass through the cuff so that the signal power equals the noise power. For slow fibres (20 m/s), the rate is 14 times lower for the multi-electrode cuff than the tripole, a significant advantage for recording from these fibres.

Estimation of peroneal and tibial afferent activity from a multichannel cuff placed on the sciatic nerve

The afferent signals recorded with a multi-electrode cuff on the sciatic nerve were employed to investigate the possibility of extracting components ascending from the peroneal and tibial nerves. Two methods, an inverse regression model and principal component method, were studied. The parameters of inverse regression model, determined by data collected in semistatic conditions, were validated by data collected in dynamic conditions. The results showed that the regression model, which used only two channels of the sciatic recordings, was sufficient to separate the distal afferent components. The model, at the expense of requiring distal branch recordings for estimating model parameters, yielded better separation than the principal component method. In conclusion, peroneal and tibial afferent activity can be estimated from the sciatic nerve: the principal component method is suitable for applications focused on acquiring afferent information, whereas the inverse regression model is better for applications in which stimulations will be applied to the branches. The estimation technique provides a powerful tool for in vivo investigation of sensory information transmitted in a peripheral nerve and facilitates implementation of advanced functional neuromuscular stimulation systems.

Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs

Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented.