Simulation of the Electrically Stimulated Cochlear Neuron: Modeling Adaptation to Trains of Electric Pulses

The Hodgkin-Huxley (HH) model does not simulate the significant changes in auditory nerve fiber (ANF) responses to sustained stimulation that are associated with neural adaptation. Given that the electric stimuli used by cochlear prostheses can result in adapted responses, a computational model incorporating an adaptation process is warranted if such models are to remain relevant and contribute to related research efforts. In this paper, we describe the development of a modified HH single-node model that includes potassium ion (K+) concentration changes in response to each action potential. This activity-related change results in an altered resting potential, and hence, excitability. Our implementation of K+-related changes uses a phenomenological approach based upon K+ accumulation and dissipation time constants. Modeled spike times were computed using repeated presentations of modeled pulse-train stimuli. Spike-rate adaptation was characterized by rate decrements and time constants and compared against ANF data from animal experiments. Responses to relatively low (250 pulse/s) and high rate (5000 pulse/s) trains were evaluated and the novel adaptation model results were compared against model results obtained without the adaptation mechanism. In addition to spike-rate changes, jitter and spike intervals were evaluated and found to change with the addition of modeled adaptation. These results provide one means of incorporating a heretofore neglected (although important) aspect of ANF responses to electric stimuli. Future studies could include evaluation of alternative versions of the adaptation model elements and broadening the model to simulate a complete axon, and eventually, a spatially realistic model of the electrically stimulated nerve within extracochlear tissues.

[1]  G. Smoorenburg,et al.  Adaptation in the compound action potential response of the guinea pig VIIIth nerve to electric stimulation , 1994, Hearing Research.

[2]  K. Osen,et al.  The cochlear nerve in the cat: Topography, cochleotopy, and fiber spectrum , 1978, The Journal of comparative neurology.

[3]  R. Smith Short-term adaptation in single auditory nerve fibers: some poststimulatory effects. , 1977 .

[5]  Jay T. Rubinstein,et al.  Comparison of Algorithms for the Simulation of Action Potentials with Stochastic Sodium Channels , 2002, Annals of Biomedical Engineering.

[6]  B. Delgutte,et al.  Auditory nerve fiber responses to electric stimulation: modulated and unmodulated pulse trains. , 2001, The Journal of the Acoustical Society of America.

[7]  Robert S Hong,et al.  Dynamic Range Enhancement for Cochlear Implants , 2003, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[8]  H. Spoendlin,et al.  Analysis of the human auditory nerve , 1989, Hearing Research.

[9]  R. Kimura,et al.  Ultrastructural study of the human spiral ganglion. , 1980, Acta oto-laryngologica.

[10]  E. Javel,et al.  Long-term adaptation in cat auditory-nerve fiber responses. , 1996, The Journal of the Acoustical Society of America.

[11]  E Wanke,et al.  A HERG‐like K+ channel in rat F‐11 DRG cell line: pharmacological identification and biophysical characterization. , 1996, The Journal of physiology.

[12]  F. Rattay,et al.  Modeling axon membranes for functional electrical stimulation , 1993, IEEE Transactions on Biomedical Engineering.

[13]  M. Liberman,et al.  Morphometry of intracellularly labeled neurons of the auditory nerve: Correlations with functional properties , 1984, The Journal of comparative neurology.

[14]  C. Stevens,et al.  Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma , 1971, The Journal of physiology.

[15]  J. Nadol,et al.  Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse , 2000, Hearing Research.

[16]  D. E. Goldman POTENTIAL, IMPEDANCE, AND RECTIFICATION IN MEMBRANES , 1943, The Journal of general physiology.

[17]  Patricia A. Leake,et al.  Cochlear pathology of long term neomycin induced deafness in cats , 1988, Hearing Research.

[18]  Vivien A. Casagrande,et al.  Biophysics of Computation: Information Processing in Single Neurons , 1999 .

[19]  J. Schwarz,et al.  Na currents and action potentials in rat myelinated nerve fibres at 20 and 37° C , 1987, Pflügers Archiv.

[20]  Paul J. Abbas,et al.  Changes Across Time in the Temporal Responses of Auditory Nerve Fibers Stimulated by Electric Pulse Trains , 2008, Journal of the Association for Research in Otolaryngology.

[21]  F. Rattay,et al.  A study of the application of the Hodgkin-Huxley and the Frankenhaeuser-Huxley model for electrostimulation of the acoustic nerve , 1986, Neuroscience.

[22]  R. Schoonhoven,et al.  Potential distributions and neural excitation patterns in a rotationally symmetric model of the electrically stimulated cochlea , 1995, Hearing Research.

[23]  Qian-Jie Fu,et al.  Effects of Stimulation Rate, Mode and Level on Modulation Detection by Cochlear Implant Users , 2005, Journal of the Association for Research in Otolaryngology.

[24]  Johan H. M. Frijns,et al.  The consequences of neural degeneration regarding optimal cochlear implant position in scala tympani: A model approach , 2006, Hearing Research.

[25]  Carolyn J. Brown,et al.  Adaptation of the Electrically Evoked Compound Action Potential (ECAP) Recorded from Nucleus CI24 Cochlear Implant Users , 2007, Ear and hearing.

[26]  Charles W. Parkins,et al.  A model of electrical excitation of the mammalian auditory-nerve neuron , 1987, Hearing Research.

[27]  John R Clay,et al.  Axonal excitability revisited. , 2005, Progress in biophysics and molecular biology.

[28]  Robert S Hong,et al.  High-rate conditioning pulse trains in cochlear implants: dynamic range measures with sinusoidal stimuli. , 2003, The Journal of the Acoustical Society of America.

[29]  Paul J. Abbas,et al.  Changes Across Time in Spike Rate and Spike Amplitude of Auditory Nerve Fibers Stimulated by Electric Pulse Trains , 2007, Journal of the Association for Research in Otolaryngology.

[30]  Stephen H Wright,et al.  Generation of resting membrane potential. , 2004, Advances in physiology education.

[31]  E Wanke,et al.  A Novel Role for HERG K+ Channels: Spike‐Frequency Adaptation , 1997, The Journal of physiology.

[32]  P J Abbas Recovering from long-term and short-term adaptation of the whole nerve action potential. , 1984, The Journal of the Acoustical Society of America.

[33]  Frank Rattay,et al.  A model of the electrically excited human cochlear neuron I. Contribution of neural substructures to the generation and propagation of spikes , 2001, Hearing Research.

[34]  Xiao-Jing Wang,et al.  Spike-Frequency Adaptation of a Generalized Leaky Integrate-and-Fire Model Neuron , 2004, Journal of Computational Neuroscience.

[35]  D T Lawson,et al.  Temporal representations with cochlear implants. , 1997, The American journal of otology.

[36]  L. Cartee,et al.  Spiral ganglion cell site of excitation II: Numerical model analysis , 2006, Hearing Research.

[37]  Carolyn J Brown,et al.  An analysis of the impact of auditory-nerve adaptation on behavioral measures of temporal integration in cochlear implant recipients. , 2005, The Journal of the Acoustical Society of America.

[38]  J T Rubinstein,et al.  Threshold fluctuations in an N sodium channel model of the node of Ranvier. , 1995, Biophysical journal.

[39]  W. Grill,et al.  Inversion of the current-distance relationship by transient depolarization , 1997, IEEE Transactions on Biomedical Engineering.

[40]  C. Koch,et al.  Multiple channels and calcium dynamics , 1989 .

[41]  E. Barrett,et al.  Separation of two voltage‐sensitive potassium currents, and demonstration of a tetrodotoxin‐resistant calcium current in frog motoneurones. , 1976, The Journal of physiology.

[42]  Robert Plonsey,et al.  Bioelectricity: A Quantitative Approach Duke University’s First MOOC , 2013 .

[43]  MO ZUN-LI,et al.  Endogenous Firing Patterns of Murine Spiral Ganglion Neurons , 1997 .

[44]  John G. Nicholls,et al.  Long-Lasting Hyperpolarization after Activity of Neurons in Leech Central Nervous System , 1968, Science.

[45]  Martin J. Pinter,et al.  Resting Potential–dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo , 2005, The Journal of general physiology.

[46]  F. Zeng Trends in Cochlear Implants , 2004, Trends in amplification.

[47]  A. Hodgkin,et al.  The effect of temperature on the electrical activity of the giant axon of the squid , 1949, The Journal of physiology.

[48]  Carson C. Chow,et al.  Spontaneous action potentials due to channel fluctuations. , 1996, Biophysical journal.

[49]  Jeroen J Briaire,et al.  Optimizing the Number of Electrodes with High-rate Stimulation of the Clarion CII Cochlear Implant , 2003, Acta oto-laryngologica.

[50]  A. Hodgkin,et al.  The after‐effects of impulses in the giant nerve fibres of Loligo , 1956, The Journal of physiology.

[51]  J. Frijns,et al.  Spatial selectivity in a rotationally symmetric model of the electrically stimulated cochlea , 1996, Hearing Research.

[52]  Frank Rattay,et al.  A model of the electrically excited human cochlear neuron. II. Influence of the three-dimensional cochlear structure on neural excitability , 2001, Hearing Research.

[53]  Paul J. Abbas,et al.  The effects of interpulse interval on stochastic properties of electrical stimulation: models and measurements , 2001, IEEE Transactions on Biomedical Engineering.

[54]  Warren M. Grill,et al.  Stimulus waveforms for selective neural stimulation , 1995 .

[55]  J. R. Clay,et al.  Relationship between membrane excitability and single channel open-close kinetics. , 1983, Biophysical journal.

[56]  J. J. Grote,et al.  The Importance of Human Cochlear Anatomy for the Results of Modiolus-Hugging Multichannel Cochlear Implants , 2001, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[57]  R. Fox Stochastic versions of the Hodgkin-Huxley equations. , 1997, Biophysical journal.

[58]  P. Stypulkowski,et al.  Physiological properties of the electrically stimulated auditory nerve. II. Single fiber recordings , 1984, Hearing Research.

[59]  William H. Press,et al.  Numerical Recipes in C, 2nd Edition , 1992 .

[60]  Yoram Palti,et al.  Potassium ion accumulation in a periaxonal space and its effect on the measurement of membrane potassium ion conductance , 1973, The Journal of Membrane Biology.

[61]  Z. Mo,et al.  Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location , 2002, The Journal of comparative neurology.

[62]  J. T Rubinstein,et al.  Pseudospontaneous activity: stochastic independence of auditory nerve fibers with electrical stimulation , 1999, Hearing Research.

[63]  Charles A. Miller,et al.  Auditory nerve responses to monophasic and biphasic electric stimuli , 2001, Hearing Research.

[64]  Paul J. Abbas,et al.  Effects of electrode-to-fiber distance on temporal neural response with electrical stimulation , 2004, IEEE Transactions on Biomedical Engineering.

[65]  Robert K. Shepherd,et al.  Electrical stimulation of the auditory nerve III. Response initiation sites and temporal fine structure , 2000, Hearing Research.

[66]  K. Plant,et al.  Speech Perception as a Function of Electrical Stimulation Rate: Using the Nucleus 24 Cochlear Implant System , 2000, Ear and hearing.

[67]  D. Baylor,et al.  Changes in extracellular potassium concentration produced by neuronal activity in the central nervous system of the leech , 1969, The Journal of physiology.

[68]  H. Mino,et al.  Effects of Neural Refractoriness on Spatio–Temporal Variability in Spike Initiations With Electrical Stimulation , 2006, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[69]  J. Nadol,et al.  Patterns of neural degeneration in the human cochlea and auditory nerve: implications for cochlear implantation. , 1997, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[70]  Jeroen J Briaire,et al.  Field patterns in a 3D tapered spiral model of the electrically stimulated cochlea , 2000, Hearing Research.

[71]  J. Nadol,et al.  Comparative anatomy of the cochlea and auditory nerve in mammals , 1988, Hearing Research.

[72]  Charles C. Finley,et al.  Models of Neural Responsiveness to Electrical Stimulation , 1990 .