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Objective: Interphase gaps (IPGs) are among the most commonly suggested pulse shape variations to try to enhance neural stimulation efficiency by reducing the action potential (AP) suppressing effect of an early anodic hyperpolarization. The majority of published literature on the effect of IPGs is based on investigations of monopolar stimulation configurations. However, many contemporary neuromodulation applications including the emerging field of electroceutical devices operate in a bipolar electrode configuration. Methods: We investigated the effect of IPGs and asymmetric biphasic current controlled pulses with reduced anodic amplitude on neural activation in both principal electrode configurations in a rodent in-vivo nerve muscle preparation. Results: In the monopolar electrode configuration, our findings of 10.9 ± 1.5% decreased stimulation amplitude with 200 μs IPGs in biphasic pulses of 40 μs phase width are in agreement with published literature in this configuration. Surprisingly, using the bipolar configuration, opposite effects of IPGs were observed and neural activation required up to 18.6 ± 3.1% (phase width 100 μs, IPG = 1000 μs) higher amplitudes. Electroneurogram recordings of the stimulated nerve revealed temporal differences in AP generation between the monopolar and bipolar configuration. In the bipolar configuration excitation first occurred in response to the middle field transition of biphasic pulses. Conclusion: This is the first study to report consistently increased amplitude requirements with IPGs in bipolar stimulation configurations. Significance: Our findings must be taken into consideration when designing stimulation waveforms for neuromodulation devices that operate in a bipolar mode to avoid increased amplitude requirements that result in increased energy consumption.

Fundamental studies in neuroimmunophysiology are the keystone for development of new therapeutic approaches to the treatment of infectious, allergic, oncologic and autoimmune diseases. The achievements in this field allowed approving new treatment methods based on irritation of afferent and efferent fibers of autonomic nerves. That became possible due to numerous studies of pathways between the immune and nervous systems performed over last two decades. The milestones in the history of neuroimmune communication research are represented here. The immune system organs – bone marrow, thymus and spleen are coupled to central nervous system (CNS) via sympathetic nerves. Information about LPS and bacteria emergence in peritoneum, intestine and parenchymal organs reaches the brain via parasympathetic pathways. After vagotomy, the brain neurons do not respond to this kind of antigens. The pattern of brain responses to different applied antigens (the EEG changes and the quantity of c-Fos-positive neurons) is specific for definite antigen, like as algorithms of electroneurogram after exposure to different cytokines. Activation of parasympathetic nerves causes the inhibition of inflammation. The entry of any antigens into the body initiates production of cytokines (IL-1, TNFα, IL-6, IFNγ etc.), via specific receptors which are present on peripheral neurons and terminals of vagus nerve, i.e. the vagal afferent terminals and neurons respond to cytokine action, and these signals are transmitted to CNS neurons. The afferent vagal fibers end on the dorsal vagal complex neurons in the caudal part of medulla oblongata. The information about bacterial antigens, LPS and inflammation is transmitted to the brain via afferent autonomic neural pathways. The speed of this process is high and significantly depends on the rates of cytokine production that are transmitters of signals upon the antigen exposure. It is important to emphasize that this events occur within minutes, and the response to the received information proceeds by reflex mechanisms, i.e., within fraction of a second, as exemplified by inflammation (“inflammation reflex”). This is a fundamentally new and revolutionary discovery in the functional studies of immune system regulation. Clinical efficiency of n. vagus stimulation by pulsed ultrasound was shown, being used for the treatment of inflammatory, allergic and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, renal inflammatory diseases. Electrical stimulation of the vagus nerve reduces the death of animals in septic shock by 80%. The mentioned data have made a revolution in understanding the functional arrangement of immune system in the body. A hypothesis is represented, which suggests how the information on the antigen exposure is transmitted to the brain.

This paper presents an ongoing development of an arm neuroprosthesis implantable interface consisting of a quadrupole implantable cuff-electrode, a neural analog front-end, a low power Arduino microcontroller, an off the shelf 433MHz transmitter, and a 3.7V 430mAh Li-Po battery. Implantable cuff electrode made of PDMS and Au has been successfully fabricated and tested for biocompatibility. A low power and low noise analog front-end were designed to filter and amplify the electroneurogram signal sensed by the cuff-electrode. The system was tested in the laboratory with input signals similar to the actual biological signals, verifying the correct operation of the implantable device. Finally, the analog front-end module was encapsulated in PDMS and implanted in the hind limb of a swine giving valuable training and knowledge for further development of the neuroprosthesis implantable interface.

International audience; Effective closed-loop neuromodulation relies on the acquisition of appropriate physiological control variables and the delivery of an appropriate stimulation signal. In particular, electroneurogram (ENG) data acquired from a set of electrodes applied at the surface of the nerve may be used as a potential control variable in this field. Improved electrode technologies and data processing methods are clearly needed in this context. In this work, we evaluated a new electrode technology based on multichannel organic electrodes (OE) and applied a signal processing chain in order to detect respiratory-related bursts from the phrenic nerve. Phrenic ENG (pENG) were acquired from nine Long Evans rats in situ preparations. For each preparation, a 16-channel OE was applied around the phrenic nerve’s surface and a suction electrode was applied to the cut end of the same nerve. The former electrode provided input multivariate pENG signals while the latter electrode provided the gold standard for data analysis. Correlations between OE signals and that from the gold standard were estimated. Signal to noise ratio (SNR) and ROC curves were built to quantify phrenic bursts detection performance. Correlation score showed the ability of the OE to record high-quality pENG. Our methods allowed good phrenic bursts detection. However, we failed to demonstrate a spatial selectivity from the multiple pENG recorded with our OE matrix. Altogether, our results suggest that highly flexible and biocompatible multi-channel electrode may represent an interesting alternative to metallic cuff electrodes to perform nerve bursts detection and/or closed-loop neuromodulation.

On-demand stimulation improves the efficacy of vagus nerve stimulation (VNS) in refractory epilepsy. The vagus nerve is the main peripheral parasympathetic connection and seizures are known to exhibit autonomic symptoms. Therefore, we hypothesized that seizure detection is possible through vagus nerve electroneurogram (VENG) recording. We developed a metric able to measure abrupt changes in amplitude and frequency of spontaneous vagus nerve action potentials. A classifier was trained using a "leave-one-out"method on a set of 6 seizures and 3 control recordings to utilize the VENG spike feature-based metric for seizure detection. We were able to detect pentylenetetrazol (PTZ) induced acute seizures in 6/6 animals during different stages of the seizure with no false detection. The classifier detected the seizure during an early stage in 3/6 animals and at the onset of tonic clonic stage of the seizure in 3/6 animals. EMG and motion artefacts often accompany epileptic activity. We showed the "epileptic"neural signal to be independent from EMG and motion artefacts. We confirmed the existence of seizure related signals in the VENG recording and proved their applicability for seizure detection. This detection might be a promising tool to improve efficacy of VNS treatment by developing new responsive stimulation systems., SCOPUS: ar.j, info:eu-repo/semantics/published

This paper demonstrates an integrated analog front-end (AFE) for measuring cutaneous neural signals, i.e, electroneurogram (ENG). The AFE outputs a latency value that indicates the time which an ENG signal travels from the first to the second electrode. This latency value is used as a parameter by physicians to diagnose disorders affecting the peripheral nervous system such as muscular dystrophy. The AFE is designed and laid out in TSMC 0.18 µm 6M1P 5 V CMOS process. Post-layout simulations show a x40k increase in ENG amplitude from the input with the EMG amplitude showing only a x4 increase, which alters the ENG to EMG ratio from 0.001 V/V to 10 V/V This is achieved with sub-mW low power consumption at a supply voltage of 1.8V.

OBJECTIVE: Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings.MATERIALS AND METHODS: The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms.RESULTS: The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (R(2) values between 0.85 and 0.99).CONCLUSIONS: The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems.

Background: The spinal cord’s central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more recently by connectome circuits. Asymmetrical models, at odds with the half-center paradigm, are composed of extensor and flexor CPG modules. Other models include not only flexor and extensor motoneurons but also motoneuron pools controlling biarticular muscles. It is unknown whether a preferred model can explain some particularities that fictive scratching (FS) in the cat presents. The first aim of this study was to investigate FS patterns considering the aiming and the rhythmic periods, and second, to examine the effects of serotonin (5HT) on and segmental inputs to FS. Methods: The experiments were carried out first in brain cortex-ablated cats (BCAC), then spinalized (SC), and for the midcollicular (MCC) preparation. Subjects were immobilized and the peripheral nerves were used to elicit the Monosynaptic reflex (MR), to modify the scratching patterns and for electroneurogram recordings. Results: In BCAC, FS was produced by pinna stimulation and, in some cases, by serotonin. The scratching aiming phase (AP) initiates with the activation of either flexor or extensor motoneurons. Serotonin application during the AP produced simultaneous extensor and flexor bursts. Furthermore, WAY 100635 (5HT1A antagonist) produced a brief burst in the tibialis anterior (TA) nerve, followed by a reduction in its electroneurogram (ENG), while the soleus ENG remained silent. In SC, rhythmic phase (RP) activity was recorded in the soleus motoneurons. Serotonin or WAY produced FS bouts. The electrical stimulation of Ia afferent fibers produced heteronymous MRes waxing and waning during the scratch cycle. In MCC, FS began with flexor activity. Electrical stimulation of either deep peroneus (DP) or superficial peroneus (SP) nerves increased the duration of the TA electroneurogram. Medial gastrocnemius (MG) stretching or MG nerve electrical stimulation produced a reduction in the TA electroneurogram and an initial MG extensor burst. MRes waxed and waned during the scratch cycle. Conclusion: Descending pathways and segmental afferent fibers, as well as 5-HT and WAY, can change the FS pattern. To our understanding, the half-center hypothesis is the most suitable for explaining the AP in MCC.

Neural interface is man-made information pathway through which biological nerve system could communicate directly with electromechanical devices including computer, robot and even cyborg. This paper introduces a novel neural interfacing electrode array capable of bidirectional information transmission and multi-signals recording. The novel flexible electrode array with 32 channels enables close-looped control and feedback neural interfacing researches with the capability of both electrical stimulation and simultaneous recording of electroencephalogram (EEG), electromyogram (EMG), electroneurogram (ENG) signals. The electrochemical impedance spectroscopy (EIS) measurement of the electrode array was carried out to evaluate the electrode array electrochemical performance in the electrophysiology frequency range. Electrical stimulation to peripheral nerve was performed with various stimulation configuration of ENG electrode site pairs to produce distinct activation patterns. Muscle action potentials of the gastrocnemius of the hind limb indicated different configuration of electrode site pairs could generate distinct stimulating effect. In addition, three groups of in vivo experiments were conducted to demonstrate the recording ability of the electrode array for nerve signals. The data from 32 channels verified the effectiveness of this flexible electrode array in simultaneous recording of EEG/EMG/ENG in vivo.

Background: The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli. This is due to the unique amenability of the unanesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation and in vivo organ imaging. Recently, there has been growing interest in pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity, metabolism, and appetite control. There is no approach to study this in utero and corresponding physiological understanding is scarce. New Method: Based on our previous presentation of a stable chronically instrumented unanesthetized fetal sheep model, here we describe the surgical instrumentation procedure allowing successful implantation of a cervical uni- or bilateral VNS probe with or without vagotomy. Results: In a cohort of 53 animals, we present the changes in blood gas, metabolic, and inflammatory markers during the postoperative period. We detail the design of a VNS probe which also allows recording from the nerve. We also present an example of vagus electroneurogram (VENG) recorded from the VNS probe and an analytical approach to the data. Comparison with Existing Methods: This method represents the first implementation of VENG/VNS in a large pregnant mammalian organism. Conclusions: This study describes a new surgical procedure allowing to record and manipulate chronically the vagus nerve activity in an animal model of human pregnancy., Accompanying data repository: https://doi.org/10.6084/m9.figshare.7228307.v2

The central nervous system regulates recruitment and firing of motor units to modulate muscle tension. Estimation of the firing rate time series is typically performed by decomposing the electromyogram (EMG) into its constituent firing times, then lowpass filtering a constituent train of impulses. Little research has examined the performance of different estimation methods, particularly in the inevitable presence of decomposition errors. The study of electrocardiogram (ECG) and electroneurogram (ENG) firing rate time series presents a similar problem, and has applied novel simulation models and firing rate estimators. Herein, we adapted an ENG/ECG simulation model to generate realistic EMG firing times derived from known rates, and assessed various firing rate time series estimation methods. ENG/ECG-inspired rate estimation worked exceptionally well when EMG decomposition errors were absent, but degraded unacceptably with decomposition error rates of ⩾1%. Typical EMG decomposition error rates-even after expert manual review-are 3-5%. At realistic decomposition error rates, more traditional EMG smoothing approaches performed best, when optimal smoothing window durations were selected. This optimal window was often longer than the 400ms duration that is commonly used in the literature. The optimal duration decreased as the modulation frequency of firing rate increased, average firing rate increased and decomposition errors decreased. Examples of these rate estimation methods on physiologic data are also provided, demonstrating their influence on measures computed from the firing rate estimate.

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 0.5 μV, 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.

The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.

Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

The adoption of chronic implantable peripheral nerve-based prosthetic devices is currently hampered by the lack of a highly integrated neural signal acquisition system-on-chip (SoC). We report a ten-channel peripheral nervous system (PNS) electroneurogram (ENG) signal acquisition SoC within an implantable package. Requiring only four off-chip capacitors, this SoC can be co-encapsulated with flexible nerve electrodes and a resonant coil antenna to form a 3.4 cm3 and 3.9 g implantable device for chronic ENG acquisition. This SoC is inductively powered and controlled through a resonant coil at 22 MHz and transmits the digitized neural signal through a near-infrared LED (NIR-LED). Fabricated in 0.18- $\mu \text{m}$ CMOS, each amplifier channel exhibits an input referred noise of 1.9 $\mu \text{V}_{\mathbf {rms}}$ and a noise efficiency factor (NEF) of 4.0 within the signal bandwidth of 5.5 kHz. Each amplifier channel within the SoC is digitized with 10-bit resolution at 17.5 ksps, and the total power consumption (SoC and NIR-LED) is 4.4 mW when the NIR-LED is driven at 3 Mb/s. An electrode impedance measurement circuit with $\text{M}\Omega $ is also incorporated in this SoC. This wireless, low noise ENG acquisition SoC package has been validated in vivo while implanted on a rodent to acquire ENG from its sciatic nerve.

Biomedical signals are collected from a body that can be at the organ level, cell level, or molecular level. There are different biomedical signals including the electroencephalogram (EEG), which is the electrical activity from the brain; the electrocardiogram (ECG), which is the electrical activity from the heart; the electromyogram (EMG), which is the electrical activity from the muscle sound signals; the electroneurogram; the electroretinogram from the eye; and so on (Muthuswamy, Biomedical signal analysis. In: Myer Kutz (ed) Standard handbook of biomedical engineering and design, vol 14. McGraw-Hill Education, New York, pp 1–18. 2004). Biomedical signals are primarily used to diagnose or detect specific pathological or physiological conditions. Additionally, these signals are employed to analyze biological systems in the healthcare. The aims of signal processing are signal denoising, precise recognition of signal model through analysis, feature extraction and dimension reduction for decisive function or dysfunction, and prediction of future functional or pathological events by employing machine learning techniques. The objective of this chapter is to present how biomedical signals are used in the healthcare and what are the steps of biomedical signal analysis.

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.

Recently, implantable devices have become widely used in neural prostheses because they eliminate endemic drawbacks of conventional percutaneous neural interface systems. However, there are still several issues to be considered: low-efficiency wireless power transmission; wireless data communication over restricted operating distance with high power consumption; and limited functionality, working either as a neural signal recorder or as a stimulator. To overcome these issues, we suggest a novel implantable wireless neural interface system for simultaneous neural signal recording and stimulation using a single cuff electrode. By using widely available commercial off-the-shelf (COTS) components, an easily reconfigurable implantable wireless neural interface system was implemented into one compact module. The implantable device includes a wireless power consortium (WPC)-compliant power transmission circuit, a medical implant communication service (MICS)-band-based radio link and a cuff-electrode path controller for simultaneous neural signal recording and stimulation. During in vivo experiments with rabbit models, the implantable device successfully recorded and stimulated the tibial and peroneal nerves while communicating with the external device. The proposed system can be modified for various implantable medical devices, especially such as closed-loop control based implantable neural prostheses requiring neural signal recording and stimulation at the same time.

The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. We recently demonstrated (Seo et al., arXiV, 2013; Seo et al., Neuron, 2016) "neural dust," a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. There, we showed that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enabled high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. In this talk, I will review recent developments from my group and collaborators in this area.

Background Sonography is a diagnostic tool with great development in diagnosing entrapment neuropathy. It9s an easy, painless, fast, non-invasive technique and can explore how the nerve9s morphology and pathologies are associated. An electroneurogram is used to assess the intensity of nerve involvement. Objectives To determine the relationship between the intensity of nerve involvement by electroneurogram and the measurement of the cross-sectional area (CSA) of the median nerve by sonography in patients with idiopathic carpal tunnel syndrome (CTS) waiting for surgery. Methods 56 wrists of 39 consecutive patients waiting for surgery were tested, however 5 were excluded because were found to have anatomic variants (4 bifid nerves, 2 median arteries) and 1 fybrolipoma. Therefore, the final sample was 51 wrists of 37 consecutive patients (11 male and 26 females), with a mean age of 59.2 years (26–85), all with electrophysiologically confirmed idiopathic CTS. Patients were classified by their electrophysiologic grade. The median nerve cross-sectional area at proximal and distal carpal tunnel was measured using high frequency ultrasound. Relationships between CSA, the severity of the electrophysiologic grade and the duration of symptoms were analysed. Also, a median nerve morphological characteristics examination (hipoecogenicity, loss of fascicular structure, Power Doppler signal and anatomical variants) was undertaken. A comparison between CSA and the severity of the electrophysiologic grade was made using an independent T test and the connection between CSA and the duration of symptoms was calculated using ANOVA test. Results Patients were classified by their electrophysiologic severity grade (8 mild, 13 moderate, 29 severe and 1 very severe). The mean ultrasound area of distal medial nerve was 8.7 mm 2 in mild-moderate and 9.2 mm 2 in severe-very severe cases (p=0.52). The average of proximal CSA was 11.6 mm 2 in mild-moderate and 14.1 mm 2 in severe-very severe cases with statistical signification differences (p=0.026). Relationship between CSA and symptom9s duration wasn9t identified. In 89.2% of the cases, hipoecogenicity and the loss of fascicular structure were observed but no cases were found to show positive Power Doppler signal. Conclusions The most valid and relevant parameter regarding the electroneurogram in the diagnosis of CTS is CSA at proximal carpal tunnel by sonography. A cross-sectional area measuring more than 9–10 mm 2 has been suggested to be pathologic and our study confirms these results. While the electroneurogram is the gold-standard method in the diagnosis of nerve involvement severity, a sonography could improve the diagnostic sensibility and give information about nerve9s morphology and associated pathologies. Disclosure of Interest None declared

ObjectiveWe aimed to refine electroneurogram techniques for monitoring hypogastric nerve activity during bladder filling, and then examined nerve activity in normal intact versus acutely decentralized bladders.MethodsEffects of electrical stimulation of hypogastric nerves or lumbar ventral roots on detrusor pressure were examined, as were effects of isoflurane versus propofol anesthetics on hypogastric nerve stimulation evoked pressure. Hypogastric nerve activity was then recorded using custom-made bipolar cuff electrodes during bladder filling before and after its transection between the spinal cord and electrode to eliminate efferent nerve signals.ResultsElectrical stimulation of hypogastric nerves evoked low amplitude detrusor pressures that did not differ between the two anesthetics. Upper lumbar (L2) ventral root stimulation evoked detrusor pressures were suppressed, yet not eliminated, after transection of hypogastric nerves and all spinal roots below L5. Afferent and efferent hypogastric nerve activity did not change with bladder filling in neuronally intact bladders yet decreased in decentralized bladders. No change in afferent activity was observed during bladder filling in either intact or decentralized bladders.ConclusionsThese findings indicate that a more complete decentralized bladder model should include transection of lumbosacral spinal roots innervating the bladder as well as hypogastric nerves. These refined electroneurogram recording methods may be suitable for evaluating the effectiveness of nerve transfer surgeries for bladder reinnervation by monitoring sensory activity in the transferred nerve.

Although it is known that the generation of movements is performed to a large extent in neuronal circuits located in the spinal cord, the involved mechanisms are still unclear. The turtle as a model system for investigating spinal motor activity has advantages, which far exceeds those of model systems using other animals. The high resistance to anoxia allows for investigation of the fully developed and adult spinal circuitry, as opposed to mammals, which are sensitive to anoxia and where using neonates are often required to remedy the problems. The turtle is mechanically stable and natural sensory inputs can induce multiple complex motor behaviors, without the need for application of neurochemicals. Here, we provide a detailed protocol of how to make the adult turtle preparation, also known as the integrated preparation for electrophysiological investigation. Here, the hind-limb scratch reflex can be induced by mechanical sensory activation, while recording single cells, and the network activity, via intracellular-, extracellular- and electroneurogram recordings. The preparation was developed for the studies by Petersen et al. (2014) and Petersen and Berg (2016), and other ongoing studies.

In the development of neuroprostheses to restore sensory and motor function to disabled patients the choice of the electrodes to be used remains an important consideration. The optimal electrode design should be minimally invasive and be capable of recording or stimulating selectively a large number of nerve fibers. Additionally, the electrodes should be capable of delivering stimulation within electrochemically safe limits. Here we report on the use of a multi-contact cuff electrode for stimulation and recording from peripheral nerves. Nerve cuffs with 16 electrodes, comprising 4 rings of 4 electrodes, were implanted around the sciatic nerve of two rats. The electromyogram signal (EMG) was recorded in response to electrical stimulation delivered by the electrodes, and the electroneurogram signal (ENG) was recorded in response to sensory stimulation applied to the ipsilateral foot. Visually detectable muscle movements were elicited with charge injections ranging from 4.6 to 8.2 nC. ENG recordings in response to sensory stimulus allowed for the onset and culmination of sensory stimulation to be detected using mean absolute value of the signal. Initial results indicate that flexion and extension of the ankle joint can be differentiated by combining information recorded from pairs of electrodes. The results of this study indicate that multi-contact cuffs can be used for decoding neural signals; however, more data needs to be collected for classification of sensory movements to be tested.

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.

A novel dissection and recording technique is described for monitoring afferent firing evoked by mechanical displacement of hairs in the mouse pinna. The technique is very cost-effective and easily undertaken with materials commonly found in most electrophysiology laboratories, or easily purchased. The dissection is simple and fast, with the mechanical displacement provided by a generic electroceramic wafer controlled by proprietary software. The same software also records and analyses the electroneurogram output. The recording of the evoked nerve activity is through a commercial differential amplifier connected to fire-polished standard glass microelectrodes. Helpful tips are given for improving the quality of the preparation, the stimulation and the recording conditions to optimize recording quality. The system is suitable for assaying the electrophysiological and optical properties of lanceolate terminals of palisade endings of hair follicles, as well as the outcomes from their pharmacological and/or genetic manipulation. An example of combining electrical recording with mechanical stimulation and labeling with a styryl pyridinium vital dye is given.

The midline electroneurography (ENoG) method might reflect total facial nerve degeneration.We compared ENoG values in patients with facial palsy using two different methods, the midline method and five electroneurogram recordings, to reveal whether the ENoG value obtained with the midline method reflects total facial nerve degeneration.Forty patients with facial palsy were enrolled. Compound muscle action potentials (CMAPs) were recorded using the midline method, in which the anode was placed on the mental protuberance and the cathode was placed on the philtrum. Additionally, five electroneurogram recordings were obtained by placing the anode on the skin of the parietal region and five cathodes on the skin over five facial muscles (frontalis, orbicularis oculi, nasalis, orbicularis oris, and depressor anguli oris muscles). ENoG values recorded using the two methods were compared.The ENoG values of the five facial muscles did not differ from those obtained using the midline method. The total ENoG value calculated by summing five CMAPs from five facial muscles, which is considered to reflect total facial nerve degeneration, was not significantly different from that using midline methods; moreover, a strong positive correlation coefficient (r = 0.87) was found between them.

Cuff electrodes are effective for chronic electroneurogram (ENG) recording while minimizing nerve damage. However, the ENG signals are usually contaminated by electromyogram (EMG) activity from the surrounding muscles, stimulus artifacts produced by the electrical stimulation and noise generated in the first stage of the neural signal amplifier. This paper proposed a new cuff electrode to reduce the interference from EMG signals and stimulus artifacts. As a result, when an additional middle electrode was placed at the center of the cuff electrode, a significant improvement in the signal-to-interference ratio was achieved at 11% for the EMG signals and 12% for the stimulus artifacts when compared to a conventional tripolar cuff. Furthermore, a new low-noise amplifier was proposed to improve the signal-to-noise ratio. The circuit was designed based on a noise analysis to minimize the noise, and the results show that the total noise of the amplifier was below 1 μV for a cuff impedance of 1 kΩ and a frequency bandwidth of 300 to 5000 Hz.

The vagus nerves convey both afferent and efferent information about autonomic activity related to cardiovascular functions. Those functions have been shown to change due to epileptic seizures, which suggests that ictal events might be detected via the vagus electroneurogram (VENG). In this study, we characterize the association of ictal and peri-ictal VENG with cardiac parameters. The electrocorticogram (ECoG), electrocardiogram, and the VENG were recorded in anesthetized rats, which were intravenously infused with either a pentylenetetrazole (PTZ) solution (PTZ-lot, n = 11) or saline (control-lot, n = 6). Control animals were subsequently vagotomized and also infused with a PTZ solution (n = 5, V-PTZ-lot). Cardiac and VENG parameters were assessed during different ECoG stages of ictal activity. None of the parameters changed in the control-lot. PTZ infusion induced seizures in all rats. Cardiac-related VENG showed distinctive firing patterns for the left and right vagus nerves. Significant ictal and post-ictal changes were seen in both the left and the right VENG in association with cardiac changes and increased parasympathetic influence on the heart. Changes in VENG parameters might provide a new way to assess the ictal state of patients, which could be suitable for triggering on-demand vagus nerve stimulation.

Cuff electrodes have a benefit for chronic electroneurogram(ENG) recording while minimizing nerve damage. However, the ENG signals are usually contaminated by electromyogram(EMG) activity from the surrounding muscle, the thermal noise generated within the source resistance, and the electric noise generated primarily at the first stage of the amplifier. This paper proposes a new cuff electrode to reduce the interference of EMG signals. An additional middle electrode was placed at the center of cuff electrode. As a result, the proposed cuff electrode achieved a higher signal-to-interference ratio compared to the conventional tripolar cuff. The cuff electrode was then assembled together with closure, headstage, and hermetic case including electronic circuits. This paper also presents a lownoise amplifier system to improve signal-to-noise ratio. The circuit was designed based on the noise analysis to minimize the electronic noise. The result shows that the total noise of the amplifier was below for a cuff impedance of and the common-mode rejection ratio was 115 dB at 1 kHz. In the current study, the performance of nerve cuff electrode system was evaluated by monitoring afferent nerve signals under mechanical stimuli in a rat animal model.

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.

Problem statement: The social demands for the Quality Of Life (QOL) are increasing with the exponentially expanding silver generation. To i mprove the QOL of the disabled and elderly people, robotic researchers and biomedical engineers have b een trying to combine their techniques into the rehabilitation systems. Various biomedical signals (biosignals) acquired from a specialized tissue, or gan, or cell system like the nervous system are the driv ing force for the entire system. Examples of biosig nals include Electro-Encephalogram (EEG), Electrooculogram (EOG), Electroneurogram (ENG) and (EMG). Approach: Among the biosignals, the research on EMG signal processing and controlling is currently expanding in various directions. EMG signal based r esearch is ongoing for the development of simple, robust, user friendly, efficient interfacing device s/systems for the disabled. The advancement can be observed in the area of robotic devices, prosthesis limb, exoskeleton, wearable computer, I/O for virt ual reality games and physical exercise equipments. An EMG signal based graphical controller or interfacin g system enables the physically disabled to use word processing programs, other personal computer software and internet. Results: Depending on the application, the acquired and pro cessed signals need to be classified for interpreting into mechanical forc e or machine/computer command. Conclusion: This study focused on the advances and improvements on different methodologies used for EMG signal classification with their efficiency, flexibility a nd applications. This review will be beneficial to the EMG signal researchers as a reference and comparison st udy of EMG classifier. For the development of robust, flexible and efficient applications, this study ope ned a pathway to the researchers in performing futu re comparative studies between different EMG classific ation methods.

This paper describes the design of an implantable system for velocity-selective electroneurogram (ENG) recording. The system, which relies on the availability of multielectrode nerve cuffs (MECs) consists of two CMOS ASICs. One ASIC called the electrode unit (EU) is a mixed analogue/digital signal acquisition system which is mounted directly on an MEC in order to optimize the interface between the two. It is linked to the other ASIC by means of a 5-core cable through which it receives power and commands in addition to transmitting data. The second ASIC, called the monitoring unit (MU) manages the interface between the EUs (each MU can control up to three EUs) and an RF transcutaneous link to the external signal processor. The ASICs are fabricated in 0.8 μm CMOS technology. The EUs measure 3 mm × 4 mm each and consume 105 mW (35 mW each), while the MU measures 1.5 mm × 2 mm and consumes 4 mW. The power consumption on the communication channels (including cable losses) between the MU and EUs is 129 mW. A digital communication strategy between the two parts of the implanted system and the external controller is described.

The noise from Pt electrodes has not been measured before. We measured the impedance and noise between pairs of Pt electrodes in cylindrical cells within frequency bands which contain the electroneurogram band (ENG, 500-10 kHz). The results show that the noise from the Pt-saline interface and also the volume conductor are the same as the thermal noise from the real part of those impedances. This means that Pt electrodes are convenient for neural recording because the total source noise from the electrodes and the volume conductor (tissue) can be estimated from the measured total impedance and calculating the thermal noise associated with the resistive part. This differs from Ag/AgCl electrodes for which the interface noise has been reported to be higher than the thermal noise, and therefore calculation of the total noise will be more difficult.

Individuals with spinal cord injury or neurological disorders have problems in urinary bladder storage and in voiding function. In these people, the detrusor of bladder contracts at low volume and this causes incontinence. The goal of bladder control is to increase the bladder capacity by electrical stimulation of relative nerves such as pelvic nerves, sacral nerve roots or pudendal nerves. For this purpose, the bladder pressure has to be monitored continuously. In this paper, we propose a method for real-time estimating the bladder pressure using artificial neural network. The method is based upon measurements of electroneurogram (ENG) signal of pudendal nerve. This approach yields synthetic bladder pressure estimates during bladder contraction. The experiments were conducted on three rats. The results show that neural predictor can provide accurate estimation and prediction of bladder pressure with good generalization ability. The average error of 1-second and 5-second ahead prediction of bladder pressure are 9.62% and 10.54%, respectively.

Background: The objective of this review was to evaluate the clinical and electrophysiological findings of eight obese patients following a weight loss of more than 25 kg through diet, bariatric surgery or anorexia nervosa, coming out with peripheral nerves compression signs and symptoms. Methods: Eight patients were studied; seven of them had walking difficulty, detecting clinical evidence of common fibular nerve injury, and another one shows unilateral ulnar nerve injury. Neurophysiological study was performed: Electromyogram (EMG). Electroneurogram (ENG): Motor and sensory conduction. Late F responses and H reflex. Results: The common fibular nerve compression (seven patients) and ulnar compression (one patient) was confirmed by appropriate electrophysiological procedures. Widespread pathology is rejected. Conclusion: In the peripheral nerve compression pathology there are multiple factors to consider and many neurophysiological procedures available to diagnose it. Excessive weight loss is an exceptional cause but it is essential to think about it as diagnostic, and the correct treatment will avoid an unnecessary surgical decompression.

This article investigates various neural machine interfaces for voluntary control of externally powered upper-limb prostheses. Epidemiology of upper limb amputation, as well as prescription and follow-up studies of externally powered upper-limb prostheses are discussed. The use of electromyographic interfaces and peripheral nerve interfaces for prosthetic control, as well as brain machine interfaces suitable for prosthetic control, are examined in detail along with available clinical results. In addition, studies on interfaces using muscle acoustic and mechanical properties and the problem of interfacing sensory information to the nervous system are discussed.