Comparison of Multi-Compartment Cable Models of Human Auditory Nerve Fibers

Background: Multi-compartment cable models of auditory nerve fibers have been developed to assist in the improvement of cochlear implants. With the advancement of computational technology and the results obtained from in vivo and in vitro experiments, these models have evolved to incorporate a considerable degree of morphological and physiological details. They have also been combined with three-dimensional volume conduction models of the cochlea to simulate neural responses to electrical stimulation. However, no specific rules have been provided on choosing the appropriate cable model, and most models adopted in recent studies were chosen without a specific reason or by inheritance. Methods: Three of the most cited biophysical multi-compartment cable models of the human auditory nerve, i.e., Rattay et al. (2001b), Briaire and Frijns (2005), and Smit et al. (2010), were implemented in this study. Several properties of single fibers were compared among the three models, including threshold, conduction velocity, action potential shape, latency, refractory properties, as well as stochastic and temporal behaviors. Experimental results regarding these properties were also included as a reference for comparison. Results: For monophasic single-pulse stimulation, the ratio of anodic vs. cathodic thresholds in all models was within the experimental range despite a much larger ratio in the model by Briaire and Frijns. For biphasic pulse-train stimulation, thresholds as a function of both pulse rate and pulse duration differed between the models, but none matched the experimental observations even coarsely. Similarly, for all other properties including the conduction velocity, action potential shape, and latency, the models presented different outcomes and not all of them fell within the range observed in experiments. Conclusions: While all three models presented similar values in certain single fiber properties to those obtained in experiments, none matched all experimental observations satisfactorily. In particular, the adaptation and temporal integration behaviors were completely missing in all models. Further extensions and analyses are required to explain and simulate realistic auditory nerve fiber responses to electrical stimulation

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

A phenomenological model of the electrically stimulated auditory nerve fiber: temporal and biphasic response properties

We present a phenomenological model of electrically stimulated auditory nerve fibers (ANFs). The model reproduces the probabilistic and temporal properties of the ANF response to both monophasic and biphasic stimuli, in isolation. The main contribution of the model lies in its ability to reproduce statistics of the ANF response (mean latency, jitter, and firing probability) under both monophasic and cathodic-anodic biphasic stimulation, without changing the model's parameters. The response statistics of the model depend on stimulus level and duration of the stimulating pulse, reproducing trends observed in the ANF. In the case of biphasic stimulation, the model reproduces the effects of pseudomonophasic pulse shapes and also the dependence on the interphase gap (IPG) of the stimulus pulse, an effect that is quantitatively reproduced. The model is fitted to ANF data using a procedure that uniquely determines each model parameter. It is thus possible to rapidly parameterize a large population of neurons to reproduce a given set of response statistic distributions. Our work extends the stochastic leaky integrate and fire (SLIF) neuron, a well-studied phenomenological model of the electrically stimulated neuron. We extend the SLIF neuron so as to produce a realistic latency distribution by delaying the moment of spiking. During this delay, spiking may be abolished by anodic current. By this means, the probability of the model neuron responding to a stimulus is reduced when a trailing phase of opposite polarity is introduced. By introducing a minimum wait period that must elapse before a spike may be emitted, the model is able to reproduce the differences in the threshold level observed in the ANF for monophasic and biphasic stimuli. Thus, the ANF response to a large variety of pulse shapes are reproduced correctly by this model

Computational evaluation of cochlear implant surgery outcomes accounting for uncertainty and parameter variability

Cochlear implantation (CI) is a complex surgical procedure that restores hearing in patients with severe deafness. The successful outcome of the implanted device relies on a group of factors, some of them unpredictable or difficult to control. Uncertainties on the electrode array position and the electrical properties of the bone make it difficult to accurately compute the current propagation delivered by the implant and the resulting neural activation. In this context, we use uncertainty quantification methods to explore how these uncertainties propagate through all the stages of CI computational simulations. To this end, we employ an automatic framework, encompassing from the finite element generation of CI models to the assessment of the neural response induced by the implant stimulation. To estimate the confidence intervals of the simulated neural response, we propose two approaches. First, we encode the variability of the cochlear morphology among the population through a statistical shape model. This allows us to generate a population of virtual patients using Monte Carlo sampling and to assign to each of them a set of parameter values according to a statistical distribution. The framework is implemented and parallelized in a High Throughput Computing environment that enables to maximize the available computing resources. Secondly, we perform a patient-specific study to evaluate the computed neural response to seek the optimal post-implantation stimulus levels. Considering a single cochlear morphology, the uncertainty in tissue electrical resistivity and surgical insertion parameters is propagated using the Probabilistic Collocation method, which reduces the number of samples to evaluate. Results show that bone resistivity has the highest influence on CI outcomes. In conjunction with the variability of the cochlear length, worst outcomes are obtained for small cochleae with high resistivity values. However, the effect of the surgical insertion length on the CI outcomes could not be clearly observed, since its impact may be concealed by the other considered parameters. Whereas the Monte Carlo approach implies a high computational cost, Probabilistic Collocation presents a suitable trade-off between precision and computational time. Results suggest that the proposed framework has a great potential to help in both surgical planning decisions and in the audiological setting process

Maturation of NaV and KV channel topographies in the auditory nerve spike initiator before and after developmental onset of hearing function

Auditory nerve excitation and thus hearing depend on spike-generating ion channels and their placement along the axons of auditory nerve fibers (ANFs). The developmental expression patterns and native axonal locations of voltage-gated ion channels in ANFs are unknown. Therefore, we examined the development of heminodes and nodes of Ranvier in the peripheral axons of type I ANFs in the rat cochlea with immunohistochemistry and confocal microscopy. Nodal structures presumably supporting presensory spiking formed between postnatal days 5 (P5) and P7, including Ankyrin-G, NaV1.6, and Caspr. These immature nodal structures lacked low-voltage-activated KV1.1 which was not enriched at juxtaparanodes until approximately P13, concurrent with the developmental onset of acoustic hearing function. Anatomical alignment of ANF spike-initiating heminodes relative to excitatory input from inner hair cell (IHC) ribbon synapses continued until approximately P30. High-voltage-activated KV3.1b and KV2.2 were expressed in mutually exclusive domains: KV3.1b was strictly localized to nodes and heminodes, whereas KV2.2 expression began at the juxtaparanodes and continued centrally along the first internode. At spike-initiating heminodes in the distal osseous spiral lamina, NaV1.1 partly overlapped NaV1.6 and ankyrin-G. ANFs displayed KV7.2 and KV7.3 at heminodes, nodes, internodes, and the unmyelinated synaptic terminal segments beneath IHCs in the organ of Corti. In response to sound, spikes are initiated at the heminode, which is tightly coupled to the IHC ribbon synapse ∼20–40 μm away. These results show that maturation of nodal alignment and ion channel content may underlie postnatal improvements of ANF excitability and discharge synchrony.SIGNIFICANCE STATEMENTAcoustic and electrical hearing depends on rapid, reliable, and precise spike generation in auditory nerve fibers. A limitation of current models and therapies is a lack of information on the identities and topographies of underlying ion channels. We report the developmental profile of the auditory nerve spike generator with a focus on NaV1.1, NaV1.6, KV1.1, KV2.2, KV3.1b, KV7.2, and KV7.3 in relation to the scaffold ankyrin-G. Molecular anatomy of the spike generator matures in the weeks after developmental onset of hearing function. Subcellular positioning of voltage-gated ion channels will enable multicompartmental modeling of auditory nerve responses elicited by afferent chemical neurotransmission from hair cells and modulated by efferent neurotransmitters or evoked by extracellular field stimulation from a cochlear implant.</jats:p

Inner-Hair Cells Parameterized-Hardware Implementation for Personalized Auditory Nerve Stimulation

In this paper the hardware implementation of an inner hair cell model is presented. Main features of the design are the use of Meddis’ transduction structure and the methodology for Design with Reusability. Which allows future migration to new hardware and design refinements for speech processing and custom-made hearing aid

Temporal integration in cochlear implants and the effect of high pulse rates

Although cochlear implants (CIs) have proven to be an invaluable help for many people afflicted with severe hearing loss, there are still many hurdles left before a full restoration of hearing. A better understanding of how individual stimuli in a pulse train interact temporally to form a conjoined percept, and what effects the stimulation rate has on the percept of loudness will be beneficial for further improvements in the development of new coding strategies and thus in the quality of life of CI-wearers. Two experiments presented here deal on the topic of temporal integration with CIs, and raise the question of the effects of the high stimulation rates made possible by the broad spread of stimulation. To this effect, curves of equal loudness were measured as a function of pulse train length for different stimulation characteristics. In the first exploratory experiment, threshold and maximum acceptable loudness (MAL) were measured, and the existence and behaviour of the critical duration of integration in cochlear implants is discussed. In the second experiment, the effect of level was further investigated by including MAL measurements at shorter durations, as well as a line of equal loudness at a comfortable level. It is found that the amount of temporal integration (the slope of integration as a function of duration) is greatly decreased in electrical hearing compared to acoustic hearing. The higher stimulation rates seem to have a compensating effect on this, increasing the slope with increasing rate. The highest rates investigated here lead to slopes that are even comparable to those found in persons with normal hearing and hearing impaired. The rate also has an increasing effect on the dynamic range, which is otherwise taken to be a correlate of good performance. The values presented here point towards larger effects of rate on dynamic range than what has been found so far in the literature for more moderate ranges. While rate effects on threshold, dynamic range and integration slope seem to act uniformly for the different test subjects, the critical duration of integration varies strongly but in a non-consistent way, possibly reflecting more central, individual-specific effects. Additionally, measurements on the voltage spread of human CI-wearers are presented which are used to validate a 3D computational model of the human cochlea developed in our group. The theoretical model falls squarely inside of the distribution of measurements. A single, implant dependent voltage-offset seems to adequately explain most of the variability

Temporal integration in cochlear implants and the effect of high pulse rates

Although cochlear implants (CIs) have proven to be an invaluable help for many people afflicted with severe hearing loss, there are still many hurdles left before a full restoration of hearing. A better understanding of how individual stimuli in a pulse train interact temporally to form a conjoined percept, and what effects the stimulation rate has on the percept of loudness will be beneficial for further improvements in the development of new coding strategies and thus in the quality of life of CI-wearers. Two experiments presented here deal on the topic of temporal integration with CIs, and raise the question of the effects of the high stimulation rates made possible by the broad spread of stimulation. To this effect, curves of equal loudness were measured as a function of pulse train length for different stimulation characteristics. In the first exploratory experiment, threshold and maximum acceptable loudness (MAL) were measured, and the existence and behaviour of the critical duration of integration in cochlear implants is discussed. In the second experiment, the effect of level was further investigated by including MAL measurements at shorter durations, as well as a line of equal loudness at a comfortable level. It is found that the amount of temporal integration (the slope of integration as a function of duration) is greatly decreased in electrical hearing compared to acoustic hearing. The higher stimulation rates seem to have a compensating effect on this, increasing the slope with increasing rate. The highest rates investigated here lead to slopes that are even comparable to those found in persons with normal hearing and hearing impaired. The rate also has an increasing effect on the dynamic range, which is otherwise taken to be a correlate of good performance. The values presented here point towards larger effects of rate on dynamic range than what has been found so far in the literature for more moderate ranges. While rate effects on threshold, dynamic range and integration slope seem to act uniformly for the different test subjects, the critical duration of integration varies strongly but in a non-consistent way, possibly reflecting more central, individual-specific effects. Additionally, measurements on the voltage spread of human CI-wearers are presented which are used to validate a 3D computational model of the human cochlea developed in our group. The theoretical model falls squarely inside of the distribution of measurements. A single, implant dependent voltage-offset seems to adequately explain most of the variability

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction and reports on seven research projects.National Institutes of Health Grant P01-DC-00119National Institutes of Health Grant R01-DC-00194National Institutes of Health Grant R01 DC00238National Institutes of Health Grant R01-DC02258National Institutes of Health Grant T32-DC00038National Institutes of Health Grant P01-DC00361National Institutes of Health Grant 2RO1 DC00235National Institutes of Health Contract N01-DC2240

Towards a better speech processor for cochlear implants : auditory- nerve responses to high-rate electric pulse trains

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2002.Includes bibliographical references (p. 169-184).This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cochlear implants are prosthetic devices that seek to restore hearing in profoundly deaf patients by electrically stimulating the auditory-nerve (AN). With current implants, the representation of the sound waveform in temporal discharge patterns of the auditory nerve is severely distorted. The distortion is particularly significant at higher (>600 Hz) frequencies, for which the period of the electric stimulus is near the AN refractory period. For example, in response to a 1000-Hz pulse train, most AN fibers may fire on every other stimulus cycle, so that the AN population would represent half of the stimulus frequency rather than the actual frequency. Rubinstein et al. [Hearing. Res. 127, 108] proposed that the coding of electric waveforms in cochlear implants can be improved if a sustained, electric high-rate (5 kpps) desynchronizing pulse train (DPT) is presented in addition to the information-carrying electric stimulus. The DPT may amplify the inherent noise in ANfibers so as to produce ongoing, stochastic discharges similar to the spontaneous activity in a healthy hear. We tested this hypothesis by recording responses of ANfibers of deafened cats to sustained electric pulse trains. For most fibers, responses to the DPT showed adaptation during the first 2 minutes, followed by a sustained response for the remainder of the 10-minute stimulus. These sustained responses partially resembled spontaneous activity in terms of discharge rate and interspike interval distributions. AN fibers were extremely sensitive to modulations of the DPT, responding tomodulations as small as 0.5%.(cont.) Responses to sinusoidal modulations resembled AN responses to pure tones over a 15-25 dB range of modulation depths. Responses to complex modulations simultaneously represented several spectral components of the modulator in their temporal discharge patterns. However, for modulation depths above 10%, the representation of both sinusoidal and complex modulators was more distorted. These results demonstrate that strategies that incorporate a DPT, and that use low modulation depths to encode sounds, may evoke AN responses that more accurately represent the modulator in their temporal discharge patterns. If the central nervous system can utilize this information, then these strategies may substantially improve performance enjoyed by cochlear implant users.by Leonid Litvak.Ph.D