Responses Of Nerve Fibers Research Articles

Influence of cellular structures of skin on fiber activation thresholds and computation cost

Electrical neuromodulation is widely used to treat and manage neurological disorders. Migraine, a socioeconomic burden, may be treated using this technique. Transcutaneous stimulation of frontal nerves by electrodes placed on the forehead is of interest as it exposes patients to lower levels of risk and side-effects compared with surgical and pharmaceutical solutions and may be readily delivered. The size, shape and placement of the electrodes can be optimised using computational models involving a volume conductor model of anatomical structures and electrodes as well as nerve fibre models. A detailed volume conductor incorporating cell level structures of skin can yield an accurate map of electrical potential distribution due to an electrode setting. However, such a model imposes a very substantial computational cost which may impede the design process. Computation cost can be significantly reduced if the skin microscopic structures are ignored. In this study, we compare the accuracy and computation cost with and without skin microscopic structures on the outcome of a device for transcutaneous frontal nerve stimulation. The performance is presented as the percentage activation of target nerve fibres in response to the level of stimulus current delivered via surface electrodes placed on the forehead. When cell level structures of skin are not incorporated, discretisation time is reduced from 21 h to 0.4 h and the number of finite elements used from 18 M to 1.4 M. Only 1% difference in stimulus current thresholds is observed.

Measuring speech perception with recovered envelope cues using the peripheral auditory model

Speech perception refers to how understandable speech produced by a speaker would be by a listener. The human auditory system usually interprets this information using both envelope (ENV) and temporal fine structure (TFS) cues. While ENV is sufficient for understanding speech in quiet, TFS cues are necessary for speech segregation in noisy conditions. In general, ENV can be recovered from the TFS (known as recovered ENV); however, the degree of ENV recovery and its significance on speech perception are not clearly known/understood. In order to systematically assess the relative contribution of the recovered ENV for speech perception, this study proposes a new speech perception metric. The proposed metric employs a phenomenological model of the auditory periphery developed by Zilany and colleagues (J. Acoust. Soc. Am. 126, 283–286, 2014) to simulate the responses of the auditory nerve fibers to both original and recovered ENV cues. The performance of the proposed metric was evaluated under different types of noise (both steady-state and fluctuating noise), as well as several classes of distortion (e.g., peak-clipping, center-clipping, and phase jitter). Finally, to validate the proposed metric, the predicted scores were compared with subjective evaluation scores from behavioral studies. The proposed metric indicates a statistically significant correlation for all cases and accounts for a wider dynamic range compared to the existing metrics.

Measurements and models of auditory nerve spike rate and timing to electrical stimulation

Physiological measurements of the response of auditory nerve (AN) fibers to electrical stimulation from a cochlear implant (CI) have in general exhibited much higher maximal entrainment rates and higher temporal precision than is observed for acoustical stimulation. However, it appears that this superior rate coding in the AN for electrical stimulation does not translate to better coding of rate in the midbrain or for the percept of temporal pitch. Similarly, the enhanced temporal precision for electrical stimulation does not lead to improved coding of interaural timing differences. In this talk, I will review physiological data and computational model simulations that indicate that the superior spike rate and timing representation for CI stimulation may only hold when considering the response of some single AN fibers to repeated identical stimuli. In fact, there is a large heterogeneity in spiking responses that can change dramatically as a function of stimulus current level. A multi-compartmental computational model will be used to demonstrate how the electrode- fiber geometry and the membrane biophysics could be contributing to these phenomena. I will also discuss the implications of the likely population response of the AN to CI stimulation for brainstem processing. [Work supported by NSERC Discovery Grant 261736.]

Towards a Complete In Silico Assessment of the Outcome of Cochlear Implantation Surgery.

Cochlear implantation (CI) surgery is a very successful technique, performed on more than 300,000 people worldwide. However, since the challenge resides in obtaining an accurate surgical planning, computational models are considered to provide such accurate tools. They allow us to plan and simulate beforehand surgical procedures in order to maximally optimize surgery outcomes, and consequently provide valuable information to guide pre-operative decisions. The aim of this work is to develop and validate computational tools to completely assess the patient-specific functional outcome of the CI surgery. A complete automatic framework was developed to create and assess computationally CI models, focusing on the neural response of the auditory nerve fibers (ANF) induced by the electrical stimulation of the implant. The framework was applied to evaluate the effects of ANF degeneration and electrode intra-cochlear position on nerve activation. Results indicate that the intra-cochlear positioning of the electrode has a strong effect on the global performance of the CI. Lateral insertion provides better neural responses in case of peripheral process degeneration, and it is recommended, together with optimized intensity levels, in order to preserve the internal structures. Overall, the developed automatic framework provides an insight into the global performance of the implant in a patient-specific way. This enables to further optimize the functional performance and helps to select the best CI configuration and treatment strategy for a given patient.

The Effect of Contact Force on the Responses of Tactile Nerve Fibers to Scanned Textures

The perception of fine textures relies on highly precise and repeatable spiking patterns evoked in tactile afferents. These patterns have been shown to depend not only on the surface microstructure and material but also on the speed at which it moves across the skin. Interestingly, the perception of texture is independent of scanning speed, implying the existence of downstream neural mechanisms that correct for scanning speed in interpreting texture signals from the periphery. What force is applied during texture exploration also has negligible effects on how the surface is perceived, but the consequences of changes in contact force on the neural responses to texture have not been described. In the present study, we measure the signals evoked in tactile afferents of macaques to a diverse set of textures scanned across the skin at two different contact forces and find that responses are largely independent of contact force over the range tested. We conclude that the force invariance of texture perception reflects the force independence of texture representations in the nerve.

Speed invariance of tactile texture perception.

The nervous system achieves stable perceptual representations of objects despite large variations in the activity patterns of sensory receptors. Here, we explore perceptual constancy in the sense of touch. Specifically, we investigate the invariance of tactile texture perception across changes in scanning speed. Texture signals in the nerve have been shown to be highly dependent on speed: temporal spiking patterns in nerve fibers that encode fine textural features contract or dilate systematically with increases or decreases in scanning speed, respectively, resulting in concomitant changes in response rate. Nevertheless, texture perception has been shown, albeit with restricted stimulus sets and limited perceptual assays, to be independent of scanning speed. Indeed, previous studies investigated the effect of scanning speed on perceived roughness, only one aspect of texture, often with impoverished stimuli, namely gratings and embossed dot patterns. To fill this gap, we probe the perceptual constancy of a wide range of textures using two different paradigms: one that probes texture perception along well-established sensory dimensions independently and one that probes texture perception as a whole. We find that texture perception is highly stable across scanning speeds, irrespective of the texture or the perceptual assay. Any speed-related effects are dwarfed by differences in percepts evoked by different textures. This remarkable speed invariance of texture perception stands in stark contrast to the strong dependence of the texture responses of nerve fibers on scanning speed. Our results imply neural mechanisms that compensate for scanning speed to achieve stable representations of surface texture.NEW & NOTEWORTHY Our brain forms stable representations of objects regardless of viewpoint, a phenomenon known as invariance that has been described in several sensory modalities. Here, we explore invariance in the sense of touch and show that the tactile perception of texture does not depend on scanning speed. This perceptual constancy implies neural mechanisms that extract information about texture from the response of nerve fibers such that the resulting neural representation is stable across speeds.

Adaptive responses of peripheral lateral line nerve fibres to sinusoidal wave stimuli.

Sensory adaptation is characterized by a reduction in the firing frequency of neurons to prolonged stimulation, also called spike frequency adaptation. This has been documented for sensory neurons of the visual, olfactory, electrosensory, and auditory system both in response to constant-amplitude and to sinusoidal stimuli, but has thus far not been described systematically for the lateral line system. We recorded neuronal activity from primary afferent nerve fibres in the lateral line in goldfish in response to sinusoidal wave stimuli. Depending on stimulus characteristics, afferent fibre responses exhibited a distinct onset followed by a decline in firing rate to an apparent steady-state level, i.e., they exhibited adaptation. The degree of adaptation, measured as the percent decrease in firing rate between onset and steady-state, increased with stimulus amplitude and frequency and with increasing steepness of the rising flank of the stimulus. This may in part be due to the velocity and/or acceleration sensitivity of the lateral line receptors. The time course of the response decline, i.e., the time course of adaptation was best-fit by a power function. This is consistent with the previous studies on spike frequency adaptation in sensory afferents of weakly electric fish.

A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. A single ANF is modeled as a network of two exponential integrate-and-fire point-neuron models, referred to as peripheral and central axons of the ANF. The peripheral axon is excited by the cathodic charge, inhibited by the anodic charge, and exhibits longer spike latencies than the central axon; the central axon is excited by the anodic charge, inhibited by the cathodic charge, and exhibits shorter spike latencies than the peripheral axon. The model also includes subthreshold and suprathreshold adaptive feedback loops which continuously modify the membrane potential and can account for effects of facilitation, accommodation, refractoriness, and spike-rate adaptation in ANF. Although the model is parameterized using data for either single or paired pulse stimulation with monophasic rectangular pulses, it correctly predicts effects of various stimulus pulse shapes, stimulation pulse rates, and level on the neural response statistics. The model may serve as a framework to explore the effects of different stimulus parameters on psychophysical performance measured in cochlear implant listeners.

Spike-timing and mean-rate coding of the temporal fine structure and envelope cues in real words

A number of studies over the past decade have argued for the importance of temporal fine structure (TFS) cues for the perception of consonants. However, recent investigations indicate that TFS cues from consonants may largely be converted into envelope (ENV) cues by narrowband cochlear filtering, such that these cues are conveyed by the mean-rate response of auditory nerve fibers rather than spike-timing cues. However, these studies used nonsense VCV syllables, and this result may not generalize to real words in which the patterns of ENV and TFS cues may be substantially different, and in which lexical context may play a role. In this study, we used a computational model of the auditory periphery and neural-based speech intelligibility predictors to investigate the TFS and ENV representation of real words from the NU-6 database. Spike-timing and mean-rate cues were evaluated for “auditory chimaeras” created from this database, in which the TFS of one signal is mixed with the ENV of another. The results indicate that the chimaera processing has a bigger impact in general on the mean-rate representation of phonemes than on the spike-timing representation, and inclusion of the spike-timing cues gives better predictions of phoneme perception. [Funded by NSERC of Canada.]

Distorted Tonotopic Coding of Temporal Envelope and Fine Structure with Noise-Induced Hearing Loss

People with cochlear hearing loss have substantial difficulty understanding speech in real-world listening environments (e.g., restaurants), even with amplification from a modern digital hearing aid. Unfortunately, a disconnect remains between human perceptual studies implicating diminished sensitivity to fast acoustic temporal fine structure (TFS) and animal studies showing minimal changes in neural coding of TFS or slower envelope (ENV) structure. Here, we used general system-identification (Wiener kernel) analyses of chinchilla auditory nerve fiber responses to Gaussian noise to reveal pronounced distortions in tonotopic coding of TFS and ENV following permanent, noise-induced hearing loss. In basal fibers with characteristic frequencies (CFs) >1.5 kHz, hearing loss introduced robust nontonotopic coding (i.e., at the wrong cochlear place) of low-frequency TFS, while ENV responses typically remained at CF. As a consequence, the highest dominant frequency of TFS coding in response to Gaussian noise was 2.4 kHz in noise-overexposed fibers compared with 4.5 kHz in control fibers. Coding of ENV also became nontonotopic in more pronounced cases of cochlear damage. In apical fibers, more classical hearing-loss effects were observed, i.e., broadened tuning without a significant shift in best frequency. Because these distortions and dissociations of TFS/ENV disrupt tonotopicity, a fundamental principle of auditory processing necessary for robust signal coding in background noise, these results have important implications for understanding communication difficulties faced by people with hearing loss. Further, hearing aids may benefit from distinct amplification strategies for apical and basal cochlear regions to address fundamentally different coding deficits. Speech-perception problems associated with noise overexposure are pervasive in today's society, even with modern digital hearing aids. Unfortunately, the underlying physiological deficits in neural coding remain unclear. Here, we used innovative system-identification analyses of auditory nerve fiber responses to Gaussian noise to uncover pronounced distortions in coding of rapidly varying acoustic temporal fine structure and slower envelope cues following noise trauma. Because these distortions degrade and diminish the tonotopic representation of temporal acoustic features, a fundamental principle of auditory processing, the results represent a critical advancement in our understanding of the physiological bases of communication disorders. The detailed knowledge provided by this work will help guide the design of signal-processing strategies aimed at alleviating everyday communication problems for people with hearing loss.

Cochlear Implant Stimulation of a Hearing Ear Generates Separate Electrophonic and Electroneural Responses.

Stimulation with cochlear implants and hearing aids is becoming more widely clinically used in subjects with residual hearing. The neurophysiological characteristics underlying electroacoustic stimulation and the mechanism of its benefit remain unclear. The present study directly demonstrates that cochlear implantation does not interfere with the normal mechanical and physiological function of the cochlea. For the first time, it double-dissociates the electrical responses of hair cells (electrophonic responses) from responses of the auditory nerve fibers (electroneural responses), with separate excited cochlear locations in the same animals. We describe the condition in which these two responses spatially overlap. Finally, the study implicates that using the clinical characteristics of stimulation makes electrophonic responses unlikely in implanted subjects.

A histamine-independent itch pathway is required for allergic ocular itch

Non-histaminergic TRPA1 neural pathway is required for the development of allergic ocular itch. Pharmacological inhibition of TRPA1 channel can lead to novel therapeutic strategies to treat ocular itch in severe allergic conjunctivitis.

Local cutaneous nerve terminal and mast cell responses to manual acupuncture in acupoint LI4 area of the rats

Previous studies have shown that the effects of manual acupuncture (MA) are contributed by collagen fibers and mast cells in local acupoints, at which acupuncture stimulation causes various afferent fiber groups to be excited. However what happens in local nerve fibers and mast cells after MA remains unclear. The aim of this study was to examine the response of cutaneous nerve fibers and mast cells to MA stimulation in acupoint Hegu (LI4). The contralateral LI4 of the same rat was used as a non-stimulated control. Immnohistochemistry analysis were carried out to observe the expression of histamine (HA), serotonin (5-HT) and nociceptive neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), in the LI4 area. Mast cells were labeled with anti-mast cell tryptase antibody and simultaneously with HA or 5-HT primary antibodies to observe their co-expression. Our results showed that SP and CGRP were expressed more highly on the cutaneous nerve fibers of LI4 after MA stimulation than that of the control. Mast cells aggregated in close proximity to the blood vessels in intra-epidermis and dermis and some of them with degranulation in the lower dermis and subcutaneous tissue of LI4. Both mast cells and their granules appeared with HA (+) and 5-HT (+) expression at stimulated L14 sites, while a few intact mast cells with a little expression of 5-HT and HA were distributed in areas of non-stimulated L14. The results indicated that local cutaneous nerve terminals and mast cells responded to MA with higher expression of SP and CGRP in nerve fibers, as well as with aggregation and degranulation of mast cells with HA and 5-HT granules at acupoint LI4. These neuroactive substances may convey signals to certain pathways that contribute to the effects of acupuncture.

A computational study to evaluate the activation pattern of nerve fibers in response to interferential currents stimulation.

Interferential current (IFC) is one of the most popular electrical currents used in electrotherapy. However, there have been limited studies investigating how this stimulation affects the nerve fibers. The aim of this computational study was to evaluate the temporal and spatial patterns of fiber activation in IFC therapy for different modulation and carrier frequencies. The interferential currents were applied by two pairs of point electrodes perpendicular to each other in an infinite homogeneous medium, and a model of myelinated nerve fibers was implemented in NEURON to study the neural response. The activation thresholds for different positions of the fiber and the resultant firing patterns were evaluated. The results suggest that the fibers may fire continuously or in bursts, with frequencies equal or higher than the modulation frequency, or may be blocked, based on their position relative to the electrodes, the modulation frequency and the stimulus strength. The results confirm traditional belief about the role of the modulation frequency in firing frequency of nerve fibers and describe a possible mechanism for less sensation of pain, due to blockage of the fibers by the high-frequency nature of the interferential currents.

Salient features of otoacoustic emissions are common across tetrapod groups and suggest shared properties of generation mechanisms

Otoacoustic emissions (OAEs) are faint sounds generated by healthy inner ears that provide a window into the study of auditory mechanics. All vertebrate classes exhibit OAEs to varying degrees, yet the biophysical origins are still not well understood. Here, we analyzed both spontaneous (SOAE) and stimulus-frequency (SFOAE) otoacoustic emissions from a bird (barn owl, Tyto alba) and a lizard (green anole, Anolis carolinensis). These species possess highly disparate macromorphologies of the inner ear relative to each other and to mammals, thereby allowing for novel insights into the biomechanical mechanisms underlying OAE generation. All ears exhibited robust OAE activity, and our chief observation was that SFOAE phase accumulation between adjacent SOAE peak frequencies clustered about an integral number of cycles. Being highly similar to published results from human ears, we argue that these data indicate a common underlying generator mechanism of OAEs across all vertebrates, despite the absence of morphological features thought essential to mammalian cochlear mechanics. We suggest that otoacoustic emissions originate from phase coherence in a system of coupled oscillators, which is consistent with the notion of "coherent reflection" but does not explicitly require a mammalian-type traveling wave. Furthermore, comparison between SFOAE delays and auditory nerve fiber responses for the barn owl strengthens the notion that most OAE delay can be attributed to tuning.

Chapter 1 - Auditory pathways: anatomy and physiology

This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described.

Effects of electrode position on spatiotemporal auditory nerve fiber responses: a 3D computational model study.

A cochlear implant (CI) is an auditory prosthesis that enables hearing by providing electrical stimuli through an electrode array. It has been previously established that the electrode position can influence CI performance. Thus, electrode position should be considered in order to achieve better CI results. This paper describes how the electrode position influences the auditory nerve fiber (ANF) response to either a single pulse or low- (250 pulses/s) and high-rate (5,000 pulses/s) pulse-trains using a computational model. The field potential in the cochlea was calculated using a three-dimensional finite-element model, and the ANF response was simulated using a biophysical ANF model. The effects were evaluated in terms of the dynamic range, stochasticity, and spike excitation pattern. The relative spread, threshold, jitter, and initiated node were analyzed for single-pulse response; and the dynamic range, threshold, initiated node, and interspike interval were analyzed for pulse-train stimuli responses. Electrode position was found to significantly affect the spatiotemporal pattern of the ANF response, and this effect was significantly dependent on the stimulus rate. We believe that these modeling results can provide guidance regarding perimodiolar and lateral insertion of CIs in clinical settings and help understand CI performance.

Reverse correlation analysis of auditory-nerve fiber responses to broadband noise in a bird, the barn owl.

While the barn owl has been extensively used as a model for sound localization and temporal coding, less is known about the mechanisms at its sensory organ, the basilar papilla (homologous to the mammalian cochlea). In this paper, we characterize, for the first time in the avian system, the auditory nerve fiber responses to broadband noise using reverse correlation. We use the derived impulse responses to study the processing of sounds in the cochlea of the barn owl. We characterize the frequency tuning, phase, instantaneous frequency, and relationship to input level of impulse responses. We show that, even features as complex as the phase dependence on input level, can still be consistent with simple linear filtering. Where possible, we compare our results with mammalian data. We identify salient differences between the barn owl and mammals, e.g., a much smaller frequency glide slope and a bimodal impulse response for the barn owl, and discuss what they might indicate about cochlear mechanics. While important for research on the avian auditory system, the results from this paper also allow us to examine hypotheses put forward for the mammalian cochlea.

Simulation of the response of nerve fibers to the applied interferential currents

Abstract Introduction: Interferential current is one of the most popular kinds of electrical stimulation that are used in electrotherapy. Despite its clinical popularity, there have been limited studies to investigate how this stimulation protocol affects the nerve fibers. This study was aimed to develop a realistic model for the stimulation of nerve fibers by interferential currents and using that to assess the spatial and temporal activation patterns of fibers in response. The effect of the modulation frequency on the resultant neural activity was also evaluated. Materials and Methods: A model of the target tissue, including the skin, fat and muscle layers was implemented in COMSOL software to obtain the potential distribution induced by the current inside the tissue. Then the MRG model of the myelinated nerve fibers in NEURON environment was used to simulate the response of fibers at different positions in the tissue. A 4 KHz carrier frequency with the modulation of 1 to 250 Hz and stimulus strength of 1 to 99 mA was used in this study. Results: The sensory fibers that are passing right beneath the electrodes are blocked in response to the applied high frequency currents and cannot conduct the action potentials. The sensory and motor fibers in other positions of the tissue can be activated based on the stimulus amplitude and the modulation frequency. The temporal activation pattern is at frequencies equal or twice of the modulation frequency. The excitation thresholds for fibers in a specific depth of the tissue are different based on their position relative to the electrodes, and even fibers that are outside the borders of the four electrodes can be activated. Conclusion: The results demonstrate how the block of sensory fibers may decrease the patient discomfort, and suggests that non-target fibers outside the region of electrode placement may also affected by the stimulation. Moreover, the results confirm the traditional claims about role of the modulation frequency in the firing frequency of nerve fibers. Keywords: Electrotherapy, Transcutaneous Electrical stimulation, Nerve fiber, Interferential Current, Simulation.

Analysis of Spatiotemporal Pattern Correction Using a Computational Model of the Auditory Periphery

The purpose of this study was to determine the cause of poor experimental performance of a spatiotemporal pattern correction (SPC) scheme that has been proposed as a hearing aid algorithm and to determine contexts in which it may provide benefit. The SPC scheme is intended to compensate for altered phase response and group delay differences in the auditory nerve spiking patterns in impaired ears. Based on theoretical models of loudness and the hypothesized importance of temporal fine structure for intelligibility, the compensations of the SPC scheme are expected to provide benefit; however, preliminary experiments revealed that listeners preferred unprocessed or minimally processed speech as opposed to complete SPC processed speech. An improved version of the SPC scheme was evaluated with a computational auditory model in response to a synthesized vowel at multiple SPLs. The impaired model auditory nerve response to SPC-aided stimuli was compared to the unaided stimuli for spectrotemporal response similarity to the healthy auditory model. This comparison included analysis of synchronized rate across auditory nerve characteristic frequencies and a measure of relative phase response of auditory nerve fibers to complex stimuli derived from cross-correlations. Analysis indicates that SPC can improve a metric of relative phase response at low SPLs, but may do so at the cost of decreased spectrotemporal response similarity to the healthy auditory model and degraded synchrony to vowel formants. In-depth analysis identifies several technical and conceptual problems associated with SPC that need to be addressed. These include the following: (1) a nonflat frequency response through the analysis-synthesis filterbank that results from time-varying changes in the relative temporal alignment of filterbank channels, (2) group delay corrections that are based on incorrect frequencies because of spread of synchrony in auditory nerve responses, and (3) frequency modulations in the processed signal created by the insertion of delays. Despite these issues, SPC provided benefit to an error metric derived from auditory nerve response cross-correlations at low SPLs, which may mean phase adjustment is achieved at the expense of other metrics, but could be beneficial for low-level speech.