Promising application of a new ulnar nerve compound muscle action potential measurement montage in amyotrophic lateral sclerosis:a prospective cross-sectional study

Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles.A new method of ulnar nerve compound muscle action potential measurement was developed in 2020,which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist.This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential.In this prospective cross-sectional study,we included 64 patients with amyotrophic lateral sclerosis and 64 age-and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital.The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage.In the controls,no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings.In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy,the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2(P<0.01).Using the new method,damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method,in particular for patients in early stage amyotrophic lateral sclerosis.In addition,the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position,and that this method is more suitable for monitoring disease progression than the traditional montage.This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.

Proper Understanding of the Nerve Impulses and the Action Potential

Neurologists define the transmission of nerve impulses across the membranes of the neural cells as a result of difference in the concentration of ions while they measured an electric potential, called as an action potential, which allows the propagation of such nerve impulses as electrical signals. Such measurements should guide them to a logical explanation of the nerve impulses as electric charges driven by the measured action potential. However, such logical conclusion, or explanation, is ignored due to a wrong definition of the flow of electric charges as a flow of electrons that cannot pass through neural networks. According to recent studies, electric charges are properly defined as electromagnetic (EM) waves whose energy is expressed as the product of its propagating electric potential times their entropy flow which is adhered to the flow of such energy. Such definition matches the logical conclusion of the nerve impulses as electric charges, as previously explained, and defines the entropy of the neural network, measured by Ammeters, in Watt or Joule/Volt. The measured entropy represents a neurodiagnostic property of the neural networks that measures its capacity to allow the flow of energy per unit action potential. Theoretical verification of the innovative definition of nerve impulses is presented by following an advanced entropy approach. A proper review of the machine records of the stimulating electric charges, used in the diagnosis of the neural networks, and the stimulated nerve impulses or stimulated responses, represents practical verifications of the innovative definitions of the electric charges and the nerve impulses. Comparing the functioning of the thermoelectric generators and the brain neurons, such neurons are defined as thermoelectric generators of the electric nerve impulses and their propagating, or action, potential.

A Study of Compound Action Potentials in Current-Coupled Tracts: the General Case

In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the paper is that, for the case of biophysically inhomogeneous axon tracts, the compound action potential is governed by a Hodgkin-Huxley like equation itself in certain cases. The paper extends an earlier result for the identical axon case.

Clinical application of electrically evoked compound action potentials

ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm.Three kinds of FDA approved cochlear implants support ECAP testing.This article is to summarize the clinical application of ECAP lest.ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery.In recent years.ECAP thresholds are also used to estimate the T levels and C levels helping programming.However,correlation between ECAP thresholds and psychophysical thresholds is affected by many factors.So far,ECAPs cannot yet be a good indicator of post-operative hearing and speech performance.

The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

The distance between the two electrode tips can greatly influence the parameters used for record- ing compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spac- ings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance be- tween two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference （however also required a higher threshold and higher supramaximal stimulus）, was found to be superior to the antidromic compound action potential.

Action potential-simulated weak electric fields can directly initiate myelination

BACKGROUND： Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath. OBJECTIVE： To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system. DESIGN AND SETTING： This single-sample observation study was performed at the 324 Hospital of Chinese PLA. MATERIALS： Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used. METHODS： Cerebral cortex was harvested from the rat to prepare a suspension [（1 2）× 10^5/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10^-2, 1×10^-3, 1×10^-4, and 1×10^-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once a day for 10 consecutive days to simulate weak negative electric fields during action potential conduction. MAIN OUTCOME MEASURES： Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry. RESULTS： On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1 × 10^-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1 × 10^-4 and 1 × 10^-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells. CONCLUSION： The local negative electric field which is generated by action potentials at 1×（10^-4-10^-3） seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.

Differences in action potential propagation speed and axon initial segment plasticity between neurons from Sprague-Dawley rats and C57BL/6 mice

Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kinetics.Most learning and memory studies at the single-neuron level have relied on the use of animal models,most notably rodents.Here,we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley(SD)rats and C57BL/6(C57)mice with genetically encoded voltage indicator(GEVI)-based voltage imaging.Our data showed that APs traveled bidirectionally in neurons from both species;forward-propagating APs(fpAPs)had a different speed than backpropagating APs(bpAPs).Additionally,we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites.Compared with rat neurons,mouse neurons exhibited higher bpAP speed and lower fpAP speed,more distally located ankyrin G(AnkG)in AISs,and longer Nav1.2 lengths in AISs.Moreover,during AIS plasticity,AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons;in mouse neurons,however,they showed a longer AnkG-labeled length and more distal Nav1.2 location.Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds,different AnkG and Nav1.2 patterns in the AIS,and different AIS plasticity properties,indicating that comparisons between these species must be carefully considered.

INTRINSIC FLUORESCENCE CHANGES IN NERVE TERMINALS,EVOKED BY ACTION POTENTIALS,ARE MODULATED BY KREBS CYCLE SUBSTRATES

Electrical stimulation of the mammalian neurohypophysial infundibular stalk evokes the entry of Nat and Ca^(2+) into the neurosecretory terminals during the action potential.These events,in turn,increase intracellular Ca^(2+) and activate NaK-and Ca-ATPases,prompting the mitochondria to increase oxidative phosphorylation which can be monitored by recording the changes in FAD and NADHfluorescence.This paper reflects our efforts to determine whether or not modulating the capacity of mitochondria to produce ATP,by changing the concentrations of two important substrates of the Krebs cycle of the nerve terminal mitochondria,pyruvate and glucose,has an effect on the intrinsicfluorescence changes triggered by action potential stimulation.

Character of diaphragm compound muscle action potential and phrenic nerve conduction time in patients with obstructive sleep apnea-hypopnea syndrome

BACKGROUND： Both hypoxia and.carbon dioxide retention can damage phrenic nerve and muscle conduction, as well as diaphragm function. Diaphragm compound muscle action potential and phrenic nerve conduction time are reliable indicators for measuring phrenic nerve and diaphragm function. OBJECTIVES： To verify the hypothesis that changes of phrenic nerve conduction time （PNCT） and diaphragm compound muscle action potential （CMAP） in obstructive sleep apnea-hypopnea syndrome （OSAHS） patients might contribute to the decline of phrenic nerve and diaphragm function. PNCT and CMAP were measured with multipair esophageal electrodes combined with unilateral magnetic stimulation. DESIGN, TIME AND SETTING： Case controlled study. The experiment was carried out in Guangzhou Institute of Respiratory Disease, Guangzhou MediCal College, from June 2005 to April 2006. PARTICIPANTS： Twenty seven OSAHS patients and eight primary snoring subjects from Guangzhou Institute of Respiratory Disease, Guangzhou Medical College were recruited and all subjects were diagnosed by polysomnography （PSG）. Sixteen healthy, non-snoring subjects in the hospital for medical examination during the same time period were selected as the control group. METHODS： Esophageal electrodes, made by Guangzhou Institute of Respiratory Disease, combined with unilateral magnetic stimulation, were used to measure PNCT and CMAP of all subjects. PNCT was defined as the time from stimulation artifact to the onset of CMAP and diaphragm CMAP amplitude was measured from peak to peak. Oxygen desaturation index and apnea-hypopnea index were measured using PSG, and their relevance to PNCT and CMAP were analyzed. PNCT and CMAP in five OSAHS patients were repeatedly measured after effective nasal continuous positive airway pressure treatment for more than 2 months. MAIN OUTCOME MEASURES： （1） PNCT and diaphragm CMAP of subjects in each group. （2） Relevance of oxygen desaturation index and apnea-hypopnea index to PNCT and CMAP. （3） Changes of PNCT and CMAP of OSAHS patients before and after treatment. RESULTS： All subjects were included in the analyzed results. （1） PNCT of the OSAHS group was significantly longer compared to that of the control and primary snore groups, while CMAP of the OSAHS group was significantly lower （P 〈 0.05）. （2） PNCT and CMAP recorded from both sides correlated significantly with oxygen desaturation index and with apnea-hypopnea index （P 〈 0.01 ）. （3） PNCT shortened significantly after effective nasal continuous positive airway pressure treatment for more than 2 months （ P 〈 0.05）. CONCLUSION： Prolongation of PNCT and decrease of CMAP might contribute to the decline of phrenic nerve and diaphragm function caused by repeated nocturnal hypoxia and carbon dioxide retention. The impairment of the phrenic nerve might also decrease diaphragm function.

Changes of Monophasic Action Potential Duration and Effective Refractory Period of Three Layers Myocardium of Canine during Acute

Summary： The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of canine in vivo was investigated. Twelve canines were divided into two groups randomly： acute ischemia （AI） group and sham operation （SO） group. By using the monophasic action potential （MAP） technique, MAP and effective refractory period （ERP） of the three layers myocardium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization （TDR） and transmural dispersion of ERP （TDE） were analyzed. The results showed that in the AI group, MAP duration （MAPD） was shortened from 201.67±21.42 ms to 169.50±13.81 ms （P〈0.05）, but ERP prolonged to varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis.

Compound muscle action potential(CMAP)scan examination of paretic and contralateral muscles reveals motor unit alterations after stroke

This study presents a novel compound muscle action potential(CMAP)examination of motor unit changes in paretic muscle post stroke.CMAP scan of the first dorsal interosseous(FDI)muscle was performed bilaterally in 16 chronic stroke subjects.Various parameters were derived from the CMAP scan to examine paretic muscle changes,including CMAP amplitude,D50,step index(STEPIX)and amplitude index(AMPIX).A significant decrease in CMAP amplitude and STEPIX was observed in paretic muscles compared with contralateral muscles(CMAP amplitude:paretic(9.0±0.5)mV,contralateral(11.3±0.9)mV,P=0.024;STEPIX:paretic 101.2±7.6,contralateral 121.9±6.5,P=0.020).No significant difference in D50 and AMPIX was observed between the paretic and contralateral sides(P>0.05).The findings revealed complex paretic muscle changes including motor unit degeneration,muscle fiber denervation,reinnervation and atrophy,providing useful insights to help understand neuromuscular mechanisms associated with weakness and other functional deterioration post stroke.The CMAP scan experimental protocols and the applied processing methods are noninvasive,convenient,and automated,offering practical benefits for clinical application.

Dendritic Morphology Affects the Velocity and Amplitude of Back-propagating Action Potentials

The back-propagating action potential(bpAP)is crucial for neuronal signal integration and synaptic plasticity in dendritic trees.Its properties(velocity and amplitude)can be affected by dendritic morphology.Due to limited spatial resolution,it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology,such as the dendrite diameter and branching pattern,using patch-clamp recording.By taking advantage of Optopatch,an all-optical electrophysiological method,we made detailed recordings of the real-time propagation of bpAPs in dendritic trees.We found that the velocity of bpAPs was not uniform in a single dendrite,and the bpAP velocity differed among distinct dendrites of the same neuron.The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated.In addition,when bpAPs passed through a dendritic branch point,their velocity decreased significantly.Similar to velocity,the amplitude of bpAPs was also positively correlated with dendritic diameter,and the attenuation patterns of bpAPs differed among different dendrites.Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results.These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs.The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology.These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology,to further illuminate the role of bpAPs in neuronal communication.

Regulation of Axon Initial Segment Diameter by COUP-TFI Fine-tunes Action Potential Generation

The axon initial segment(AIS)is a specialized structure that controls neuronal excitability via action potential(AP)generation.Currently,AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated,but how AIS diameter is regulated remains elusive.Here we report that COUP-TFI(chicken ovalbumin upstream promotor-transcription factor 1)is an essential regulator of AIS diameter in both developing and adult mouse neocortex.Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation.Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation,they strengthen and weaken,respectively,the receiving spontaneous network in mutant neurons.In contrast,overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation,but decreases the receiving spontaneous network.Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.

CHARACTERISTICS OF ACTIONPOTENTIAL AND THEIR UNDERLYING OUTWARD CURRENTS IN MAMMALIAN TASTE RECEPTOR CELLS

Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two significantly different (P<0.001) groups-fast,with short half-time durations and large outward currents (mean1.3 ms and 2.7nA),and slow,with long duration and small outward currents(mean9.2ms and 0. 29nA).AP upstrokes were conducted by TTX-sensitive sodium currents whereas the downstroke by TEA-blockable outward currents. Voltage dependent analysis of outward current separated transient and sustained components.The transient component was specifically blocked by 4-AP(1mmol/L).A calcium-dependent outward component was also revealed modulating voltage and external calcium concentration.The fast recovery phase of the AP appears related the sustained outward current whereas the after hyperpolarization(AHP) was blocked by 4AP suggesting a significant contribution of the transient component.Forskolin (FSK),which elevates cAMP,reversibly blocked the majority of the sustained current without influencing the transient. FSK greatly exaggerated the AHP without changing the spike height or duration. These data suggest that several components of the outward current contribute specifically to the gustatory AP and that the AP may be modulated by cyclic nucleotides.

THE INFLUENCE OF SAPONINS OF PANAX QUINQUEFOLIUM LEAF AND STEM ON THE SLOW ACTION POTENTIALS IN MYOCARDIUM

The effects of Saponins of Panax Quinquefolium Leaf and Stem(SPQLS)were evaluatedin the rabbit sinus node and in the guinea pig papillary muscles both showing slow responses in high[k+].and being exposed to 0.3 μmol/L verapamil using conventional microelcctrode technique.Inthe sinus node, SPQLS 100 mg/L decreased the APA and Vmax.At the concentration of 200 mg/L,in addition to further depressing the upotroke,SPQIS decreased the SP4,shortened the APD and prolonged the SCL.In the guinea Pig papillary muscle,SPQLS shortened the APD and decreased theAPA as well as Vmax in high[k+3].When verapamil was exposed to the normal Tyrode's solution,SPQLS depressed the upstroke without-affecting the APD in the guinea pig papillary muscle.Thesefindings suggest that SPQLS exerted a blockade effect on the transmembrane Ca2+ influx and Na+ influx in myocardium.

EFFECTS OF DISMERINONE ON HIGH K~＋ DEPOLARIZED SLOW RESPONSE ACTION POTENTIALS IN GUINEA PIG PAPILLARY MUSCLES

The effects of dismerinone (DMR), a derivative of milrinone, on high K+ depolarized slow response action potentials (APs) and intracellular cAMP levels were studied in guinea pig papillary muscles. DMR induced slow APs in high K+ depolorized guinea pig papillary muscles and increased APA, Vmaxand APD50 of the slow APs in dose dependent way ; cAMP levels in same preparations were elevated by DMR. These effects of DMR are similar to isoprenaline (ISO). Bead adrenocepter blocker propranolol had no influence on DMR effect. Overall, the results from this study suggested that effects of DMR were not related to Beta adrenocepter, and might be related to its inhibiting phosphodiesterase Ⅲ(PDE Ⅲ) action.

Action potential code modulates dopamine release in mouse striatum in vivo

Dopamine is a neurotransmitter crucial for movement, mood, drug addiction and many neural degeneration diseases including Parkinson’s disease. Micro electrochemical carbon

Effect of applied electric fields on supralinear dendritic integration of interneuron

Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.

Cooperative activation of sodium channels for downgrading the energy efficiency in neuronal information processing

The Hodgkin–Huxley model assumes independent ion channel activation,although mutual interactions are common in biological systems.This raises the problem why neurons would favor independent over cooperative channel activation.In this study,we evaluate how cooperative activation of sodium channels affects the neuron’s information processing and energy consumption.Simulations of the stochastic Hodgkin–Huxley model with cooperative activation of sodium channels show that,while cooperative activation enhances neuronal information processing capacity,it greatly increases the neuron’s energy consumption.As a result,cooperative activation of sodium channel degrades the energy efficiency for neuronal information processing.This discovery improves our understanding of the design principles for neural systems,and may provide insights into future designs of the neuromorphic computing devices as well as systematic understanding of pathological mechanisms for neural diseases.