Nerve Compound Action Potential Research Articles

SARM1 Inhibition Maintains Axonal Integrity After Rat Sciatic Nerve Transection and Repair.

Sterile alpha and TlR motif containing-1 (SARM1) protein has been demonstrated to play a critical role in the initiation of Wallerian degeneration after nerve injury. The goal of this study was to assess whether blockade of SARM1 activity inhibits Wallerian degeneration following nerve transection, potentially promoting more rapid recovery of axonal function. An adeno-associated virus plasmid encoded with a dominant-negative SARM1 protein fused with green fluorescent protein to impair SARM1 function, was injected into 24 juvenile rats to create a SARM1 dominant-negative (SARM1-DN) phenotype. Twenty-four control rats were injected with a control plasmid expressing only green fluorescent protein. Three weeks after transfection, the rats underwent unilateral sciatic nerve transection and repair. Walking track analysis and nonsurvival surgeries were performed at 2 days, 2 weeks, or 6 weeks to assess muscle strength and compound nerve action potential. Histomorphologic and electrodiagnostic studies were evaluated with mixed-effect analysis. Histomorphologic analysis showed maintenance of axons in the SARM1-DN animals at 2 weeks, with significantly improved compound nerve action potential amplitude. Muscle testing demonstrated greater gastrocnemius strength in SARM1 DN muscles at 2 days and 2weeks compared to controls, although this was not maintained at 6 weeks. Inhibition of SARM1 resulted in early increases in number and myelination of axons and action potential after sciatic nerve transection and repair in SARM1-DN rats. SARM1 inhibition may offer the potential to delay Wallerian degeneration following nerve transection and enable earlier functional recovery of motor strength. .

Ex vivo electrophysiological evaluation of peripheral nerve functioning following exposition of adult mice to the organophosphorus pesticide chlormephos.

The organophosphorus pesticide chlormephos was tested for its potential peripheral neurotoxicity by analyzing the diphasic compound action potential (CAP) of sciatic nerves isolated from adult mice chronically exposed to a sub-lethal dose of this pesticide, compared with control age-matched animals being only exposed to the vehicle. No significant modification was detected between chlormephos-exposed and control groups in their nerve responsiveness to stimulus. Furthermore, similar values of CAP kinetic variables were obtained from the two mouse groups. Finally, no abnormality concerning CAP refractory periods and responsiveness to high frequency stimulation (nerve fatigue) was exhibited by chlormephos-treated mice, when compared with control animals. These results complicate the screening for the potential neurotoxicity of organophosphates since they support the contention that the peripheral neuropathy induced by chronical exposition to sub-lethal doses of chlormephos is species dependents does not necessary correlate well with the clinical signs observed at the central nervous system level.

Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation

Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.

The therapeutic potential of 1, 25-dihydroxy vitamin D3 on cisplatin-affected neurological functions is associated with the regulation of oxidative stress and inflammatory markers as well as levels of MMP2/9.

Calcitriol as a biologically active form of vitamin D3 has beneficial effects on all body systems. This vitamin has a potent neuroprotective effect via several independent mechanisms against brain insults induced by anticancer drugs. The present study was designed to examine the neuroprotective effects of calcitriol against neurotoxicity induced by cisplatin.Induction of neurotoxicity was done with cisplatin administration (5mg/kg/week) for 5 successive weeks in male Wistar rats. The neuroprotective influence of calcitriol supplementation (100ng/kg/day for 5 weeks) was assessed through behavioral, electrophysiological, and molecular experiments.Cisplatin administration impaired spatial learning and memory and decreased prefrontal brain-derived neurotrophic factor (BDNF). Peripheral sensory neuropathy was induced through cisplatin administration. Cisplatin also reduced the amplitudes of the compound action potential of sensory nerves in electrophysiological studies. Cisplatin treatment elevated MDA levels and reduced anti-oxidant (SOD and GPx) enzymes. Pro-inflammatory cytokines (IL-1β and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were augmented through treatment with cisplatin. Learning and memory impairments along with BDNF changes caused by cisplatin were amended with calcitriol supplementation. Reduced sensory nerve conduction velocity in the cisplatin-treated group was improved by calcitriol. Calcitriol partially improved redox imbalance and diminished the pro-inflammatory cytokines and MMP-2/9 levels.Our findings showed that calcitriol supplementation can relieve cisplatin-induced peripheral neurotoxicity. Calcitriol can be regarded as a promising new neuroprotective agent.

Sonographic evaluation of peripheral nerve involvement in leprosy with electrophysiologic correlation: a cross-sectional study in sub-Himalayan region

BackgroundLeprosy is an age-old chronic infectious disease with the majority of annual new case detections from South-East Asia. The disease manifestations coupled with the stigma attached to it often creates grave socioeconomic problems. Leprosy is curable and if detected and treated in the early stages can prevent disability. Ultrasonography provides information regarding location and degree of the nerve damage, nerve morphologic alterations, echo texture, fascicular pattern and vascularity. The aim of this study was to study the ultrasonographic features of neuropathy in leprosy with electrophysiologic correlation.ResultsA total of 34 histopathological proven cases of leprosy were included in this study, which was conducted for 1 year. High-resolution ultrasound (HRUS) of a total of 204 peripheral nerves in these 34 patients, including bilateral ulnar, median and common peroneal nerves, was performed. Cross-sectional areas, nerve diameters, nerve morphology and vascularity were noted and correlated with electrophysiologic study of these nerves. The results showed that all the patients having reduced motor or sensory function [decreased compound muscle action potential (CMAP), decreased compound nerve action potential (SNAP) and increased latency] in ulnar and common peroneal nerves were thickened on HRUS (100% in ulnar and common peroneal nerves) while 92% right median and 89% left median nerves with reduced motor or sensory function showed thickening on HRUS. Also, 5.8% ulnar nerves and 11.7% common peroneal nerves showed thickening on HRUS; however, sensory or motor conduction of these nerves was unaffected on nerve conduction study (NCS). So, a positive correlation was observed for nerve involvement as detected by ultrasonographic findings of nerve hypertrophy and the electrophysiologic study. The most common finding was focal or diffuse nerve thickening. Ulnar nerve was the most commonly thickened nerve in leprosy patients with the most common location of nerve thickening at medial epicondyle.ConclusionsUltrasound and electrophysiologic study of peripheral nerves in leprosy are complimentary to each other in diagnosing leprotic neuropathy.

Astragaloside depresses compound action potential in sciatic nerve of frogs involved in L-type Ca2+-channel dependent mechanism

The sciatic nerve is the largest sensorimotor nerve within the peripheral nervous system (PNS), possessing the ability to produce endogenous neurotrophins. Compound nerve action potentials (CNAPs) are regarded as a physiological/pathological indicator to identify nerve activity in signal transduction of the PNS. Astragaloside (AST), a small-molecule saponin purified from Astragalus membranaceus, is widely used to treat chronic disease. Nonetheless, the regulatory effects of AST on the sciatic nerve remain unknown. Therefore, the present investigation was undertaken to study the effect of AST on CNAPs of frog sciatic nerves. Here, AST depressed the conduction velocity and amplitude of CNAPs. Importantly, the AST-induced responses could be blocked by a Ca2+-free medium, or by applying all Ca2+ channel antagonists (CdCl2/LaCl3) or L-type Ca2+ channel blockers (nifedipine/diltiazem), but not the T-type and P-type Ca2+ channel antagonist (NiCl2). Altogether, these findings suggested that AST may attenuate the CNAPs of frog sciatic nerves in vitro via the L-type Ca2+-channel dependent mechanisms.

Computational models of compound nerve action potentials: Efficient filter-based methods to quantify effects of tissue conductivities, conduction distance, and nerve fiber parameters.

Peripheral nerve recordings can enhance the efficacy of neurostimulation therapies by providing a feedback signal to adjust stimulation settings for greater efficacy or reduced side effects. Computational models can accelerate the development of interfaces with high signal-to-noise ratio and selective recording. However, validation and tuning of model outputs against in vivo recordings remains computationally prohibitive due to the large number of fibers in a nerve. We designed and implemented highly efficient modeling methods for simulating electrically evoked compound nerve action potential (CNAP) signals. The method simulated a subset of fiber diameters present in the nerve using NEURON, interpolated action potential templates across fiber diameters, and filtered the templates with a weighting function derived from fiber-specific conduction velocity and electromagnetic reciprocity outputs of a volume conductor model. We applied the methods to simulate CNAPs from rat cervical vagus nerve. Brute force simulation of a rat vagal CNAP with all 1,759 myelinated and 13,283 unmyelinated fibers in NEURON required 286 and 15,860 CPU hours, respectively, while filtering interpolated templates required 30 and 38 seconds on a desktop computer while maintaining accuracy. Modeled CNAP amplitude could vary by over two orders of magnitude depending on tissue conductivities and cuff opening within experimentally relevant ranges. Conduction distance and fiber diameter distribution also strongly influenced the modeled CNAP amplitude, shape, and latency. Modeled and in vivo signals had comparable shape, amplitude, and latency for myelinated fibers but not for unmyelinated fibers. Highly efficient methods of modeling neural recordings quantified the large impact that tissue properties, conduction distance, and nerve fiber parameters have on CNAPs. These methods expand the computational accessibility of neural recording models, enable efficient model tuning for validation, and facilitate the design of novel recording interfaces for neurostimulation feedback and understanding physiological systems.

Relationship between Gravidity, Parity, and Neurophysiological Features in Carpal Tunnel Syndrome (CTS) Patients with a History of Pregnancy.

It is not yet clear if gravidity and parity have any relationships with the electrodiagnostic parameters of carpal tunnel syndrome (CTS). To determine whether there is a relationship between electrodiagnostic findings, gravidity, and parity number in CTS. Female patients over 18 years of age with CTS were included in this retrospective cohort study. The gravidity/parity number, median nerve compound muscle action potential (CMAP), and compound nerve action potential (CNAP) of the patients were analyzed. The two subgroups of the Boston carpal tunnel syndrome questionnaire (BCTSQ): The Symptom Severity Scale (SSS) and Functional Severity Scale (FSS) were applied to the patients. CTS patients were divided into two groups aged at first pregnancy ≤20 years and >20 years. One hundred and eight CTS extremities (seven right-sided CTS, three left-sided CTS, 49 bilateral CTS) of 59 patients were included. The median (interquartile range: 25%-75%) number of gravidity, parity, and abortion were 3 (2-5), 3 (2-4), and 0 (0-0), respectively. Right-sided CTS patients at the age of first pregnancy ≤20 years had higher BCTSQ-SSS/FSS scores and median nerve CMAP latency compared to patients at the age of first pregnancy >20 years (P = 0.029 for SSS; P = 0.042 for FSS; and P = 0.041 for CMAP latency). A negative correlation was found between the gravidity/parity numbers and median nerve CNAP/CMAP amplitudes (P = 0.028/0.031, r = -0.293/-0.289 for CNAP amplitude; and P = 0.006/0.035, r = -0.363/-0.283 for CMAP amplitude). Neurophysiological findings worsen as the number of gravidity and parity increase. Electrodiagnostic and clinical features of CTS may be worsening in females below 20 years at first pregnancy.

Using Compound Neural Action Potentials for Functional Validation of a High-Density Intraneural Interface: A Preliminary Study.

Compound nerve action potentials (CNAPs) were used as a metric to assess the stimulation performance of a novel high-density, transverse, intrafascicular electrode in rat models. We show characteristic CNAPs recorded from distally implanted cuff electrodes. Evaluation of the CNAPs as a function of stimulus current and calculation of recruitment plots were used to obtain a qualitative approximation of the neural interface's placement and orientation inside the nerve. This method avoids elaborate surgeries required for the implantation of EMG electrodes and thus minimizes surgical complications and may accelerate the healing process of the implanted subject.

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length.

Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant. We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing. Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of "conductive hearing loss" induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear. Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant.

Visualization of axonal and volume currents in median nerve compound action potential using magnetoneurography

Visualization of axonal and volume currents in median nerve compound action potential using magnetoneurography

Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur years earlier in those that develop AD; however, it is unknown what causes these peripheral phenotypes in a disease of the brain. Exercise promotes muscle, mitochondria, and cognitive health and is proposed to be a potential therapeutic for AD, but no study has investigated how skeletal muscle adapts to exercise training in an AD-like context. Utilizing 5xFAD mice, an AD model that develops ad-like pathology and cognitive impairments around 6 mo of age, we examined in vivo neuromuscular function and exercise adapations (mitochondrial respiration and RNA sequencing) before the manifestation of overt cognitive impairment. We found 5xFAD mice develop neuromuscular dysfunction beginning as early as 4 mo of age, characterized by impaired nerve-stimulated muscle torque production and compound nerve action potential of the sciatic nerve. Furthermore, skeletal muscle in 5xFAD mice had altered, sex-dependent, adaptive responses (mitochondrial respiration and gene expression) to exercise training in the absence of overt cognitive impairment. Changes in peripheral systems, specifically neural communication to skeletal muscle, may be harbingers for AD and have implications for lifestyle interventions, like exercise, in AD.

Evidence That Ultrafast Nonquantal Transmission Underlies Synchronized Vestibular Action Potential Generation.

Amniotes evolved a unique postsynaptic terminal in the inner ear vestibular organs called the calyx that receives both quantal and nonquantal (NQ) synaptic inputs from Type I sensory hair cells. The nonquantal synaptic current includes an ultrafast component that has been hypothesized to underlie the exceptionally high synchronization index (vector strength) of vestibular afferent neurons in response to sound and vibration. Here, we present three lines of evidence supporting the hypothesis that nonquantal transmission is responsible for synchronized vestibular action potentials of short latency in the guinea pig utricle of either sex. First, synchronized vestibular nerve responses are unchanged after administration of the AMPA receptor antagonist CNQX, while auditory nerve responses are completely abolished. Second, stimulus evoked vestibular nerve compound action potentials (vCAP) are shown to occur without measurable synaptic delay and three times shorter than the latency of auditory nerve compound action potentials (cCAP), relative to the generation of extracellular receptor potentials. Third, paired-pulse stimuli designed to deplete the readily releasable pool (RRP) of synaptic vesicles in hair cells reveal forward masking in guinea pig auditory cCAPs, but a complete lack of forward masking in vestibular vCAPs. Results support the conclusion that the fast component of nonquantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimuli.SIGNIFICANCE STATEMENT The mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more presynaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of evidence in the guinea pig which reveals the most sensitive vestibular afferents are remarkably fast, much faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that demonstrates this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.

Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model.

Polyethylene glycol (PEG) can fuse severed closely apposed axolemmas and restore axonal continuity. The authors evaluated the effects of PEG fusion on functional recovery in a rodent forelimb model of peripheral nerve injury. The median nerves of male Lewis rats ( n = 5 per group) were transected and repaired with standard suture repair (SR), SR with PEG (PEG), or SR with PEG and 1% methylene blue (PEG+MB); a sham surgery group was also included. Proximal stimulation produced compound nerve and muscle action potentials recorded distally. The contralateral limb of each animal acted as an internal control for grip strength measurements. Compound nerve and muscle action potentials immediately returned in all PEG and PEG+MB animals, but not in SR animals. The PEG and PEG+MB groups demonstrated earlier return of function by postoperative day (POD) 7 (62.6 ± 7.3% and 50.9 ± 6.7% of contralateral limb grip strength, respectively) compared with the SR group, in which minimal return of function was not measurable until POD 21. At POD 98, the PEG group grip strength recovered to 77.2 ± 2.8% and the PEG+MB grip strength recovered to 79.9 ± 4.4%, compared with 34.9 ± 1.8% recovery in the SR group ( P < 0.05). The PEG and PEG+MB groups reached 50% of the sham group grip strength on POD 3.8 and POD 6.3, respectively, whereas the SR group did not reach 50% grip strength recovery of the sham group throughout the study period. PEG fusion plus neurorrhaphy with or without MB reestablished axonal continuity, shortened recovery time, and augmented functional recovery compared with suture neurorrhaphy alone. PEG fusion with neurorrhaphy may bypass Wallerian degeneration, leading to augmented and shortened functional recovery.

On the Stimulation Artifact Reduction during Electrophysiological Recording of Compound Nerve Action Potentials.

Recording neuronal activity triggered by electrical impulses is a powerful tool in neuroscience research and neural engineering. It is often applied in acute electrophysiological experimental settings to record compound nerve action potentials. However, the elicited neural response is often distorted by electrical stimulus artifacts, complicating subsequent analysis. In this work, we present a model to better understand the effect of the selected amplifier configuration and the location of the ground electrode in a practical electrophysiological nerve setup. Simulation results show that the stimulus artifact can be reduced by more than an order of magnitude if the placement of the ground electrode, its impedance, and the amplifier configuration are optimized. We experimentally demonstrate the effects in three different settings, in-vivo and in-vitro.

High frequency alternating current neurostimulation decreases nocifensive behavior in a disc herniation model of lumbar radiculopathy

BackgroundThe purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG).MethodsTo mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo., n = 18) were separated into 3 groups: NP injury + KHFAC stimulation (n = 7), NP injury + sham cuff (n = 6), and sham injury + sham cuff (n = 5). Prior to surgery and for 2 weeks following surgery, animal tactile sensitivity, gait, and static weight bearing were evaluated.ResultsKHFAC stimulation of the sciatic nerve decreased behavioral evidence of pain and disability. Without KHFAC stimulation, injured animals had heightened tactile sensitivity compared to baseline (p < 0.05), with tactile allodynia reversed during KHFAC stimulation (p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation (p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied (p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation (p < 0.05).ConclusionsKHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation.

Comparison of ulnar, median, and sural sensory nerve conduction studies between demyelinating and axonal forms of Guillain-Barré Syndrome

Background: Guillain-Barré syndrome (GBS) is an important neurological disease that can cause disability. Axonal GBS and acute inflammatory demyelinating polyradiculoneuropathy (AIDP) are two important subgroups.&#x0D; Methods: Patients with clinical and electrodiagnostic features compatible with GBS were included in this retrospective study. The patients were divided into two groups neurophysiologically as Axonal GBS and AIDP. Medical research council (MRC) scores of the patients' muscles, median / ulnar / posterior tibial / peroneal / sural nerve conduction study findings were included in the analyses. Sural sparing pattern was considered as the absence of median/ulnar compound nerve action potential (CNAP) and present sural nerve CNAP (SS-M/SS-U).&#x0D; Results: Twelve AIDP and 10 Axonal GBS patients were included in the study. MRC scores were not different between the two groups (p=0.895). CNAPs of the right median and ulnar nerves were smaller in AIDP patients than in Axonal GBS patients (p

Visualization of axonal and volume currents in median nerve compound action potential using magnetoneurography

ObjectiveReconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their relationship to potentials. MethodsThe median nerves of both upper arms of five healthy individuals were investigated. The propagating magnetic field of the action potential was recorded using magnetoneurography, reconstructed into a current, and analyzed. The currents were compared with the potentials recorded from multipolar surface electrodes. ResultsReconstructed currents could be clearly visualized. Axonal currents flowed forward or backward in the axon, arcing away from the depolarization zone, turning about the subcutaneous volume conductor, and returning to the depolarization zone. The zero-crossing latency of the axonal current was approximately the same as the peak of its volume current and the negative peak of the surface electrode potential. Volume current waveforms were proportional to the derivative of axonal ones. ConclusionsMagnetoneurography allows the visualization and quantitative evaluation of action currents. The currents in axons and in volume conductors could be clearly discriminated with good quality. Their properties were consistent with previous neurophysiological findings. SignificanceMagnetoneurography could be a novel tool for elucidating nerve physiology and pathophysiology.

Using a Facial Nerve Stimulator to Record the Auditory Nerve Compound Action Potential to Locate the Auditory Nerve During Vestibular Schwannoma Resection

Improved technology in vestibular neuroma resection and facial nerve protection has become more sophisticated, and the protection of hearing during vestibular schwannoma resection is crucial. Currently, brainstem auditory evoked potential (BAEP), cochlear electrography, and cochlear nerve compound action potential (CNAP) are frequently used. The CNAP waveform is stable; however, the recording electrode can easily affect the procedure and cannot map the auditory nerve. The purpose of the study was to explore a simple method to record the CNAP and map the auditory nerve. In this study, CNAP was recorded using a facial nerve bipolar stimulator to localize and protect the auditory nerve. The BAEP click stimulation mode was used. A bipolar stimulator was used as the recording electrode to record CNAP and locate anatomical displacement of the auditory nerve. The CNAP of 40 patients was monitored. Pure tone audiometry, speech discrimination score, and auditory evoked potential (BAEP) evaluations were performed on all patients before and after surgery. Of the 40 patients, 30 patients obtained CNAP during surgery, and the rate of CNAP obtained was significantly higher than that of BAEP. The sensitivity and specificity of decrease in CNAP in predicting significant hearing loss were 88.9% and 66.7%, respectively. The sensitivity and specificity of the disappearance of CNAP in predicting significant hearing loss were 52.9% and 92.3%, respectively. The bipolar facial nerve stimulator can locate and protect the auditory nerve by recording a stable potential. The CNAP obtained rate was significantly higher than that of BAEP. The disappearance of BAEP during acoustic neuroma monitoring can be used as a standard alert for the surgeon, and decrease in CNAP is an alert for the operator.

Auditory nerve responses to combined optogenetic and electrical stimulation in chronically deaf mice

Objective. Optogenetic stimulation of the auditory nerve offers the ability to overcome the limitations of cochlear implants through spatially precise stimulation, but cannot achieve the temporal precision nor temporal fidelity required for good hearing outcomes. Auditory midbrain recordings have indicated a combined (hybrid) stimulation approach may permit improvements in the temporal precision without sacrificing spatial precision by facilitating electrical activation thresholds. However, previous research has been conducted in undeafened or acutely deafened animal models, and the impact of chronic deafness remains unclear. Our study aims to compare the temporal precision of auditory nerve responses to optogenetic, electrical, and combined stimulation in acutely and chronically deafened animals. Methods. We directly compare the temporal fidelity (measured as percentage of elicited responses) and precision (i.e. stability of response size and timing) of electrical, optogenetic, and hybrid stimulation (varying sub-threshold or supra-threshold optogenetic power levels combined with electrical stimuli) through compound action potential and single-unit recordings of the auditory nerve in transgenic mice expressing the opsin ChR2-H134R in auditory neurons. Recordings were conducted immediately or 2–3 weeks following aminoglycoside deafening when there was evidence of auditory nerve degeneration. Main results. Results showed that responses to electrical stimulation had significantly greater temporal precision than optogenetic stimulation (p < 0.001 for measures of response size and timing). This temporal precision could be maintained with hybrid stimulation, but only when the optogenetic stimulation power used was below or near activation threshold and worsened with increasing optical power. Chronically deafened mice showed poorer facilitation of electrical activation thresholds with concurrent optogenetic stimulation than acutely deafened mice. Additionally, responses in chronically deafened mice showed poorer temporal fidelity, but improved temporal precision to optogenetic and hybrid stimulation compared to acutely deafened mice. Significance. These findings show that the improvement to temporal fidelity and temporal precision provided by a hybrid stimulation paradigm can also be achieved in chronically deafened animals, albeit at higher levels of concurrent optogenetic stimulation levels.