title: Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs: relation to neuronal status.
abstract: Successful cochlear implant performance requires adequate responsiveness of the auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the auditory nerve as a result of severe hair cell loss could considerably compromise this ability. The main objective of this study was to characterize the recovery of the electrically stimulated auditory nerve, as well as to evaluate possible changes caused by deafness-induced degeneration. To this end we studied temporal responsiveness of the auditory nerve in a guinea pig model of sensorineural hearing loss. Using masker-probe and pulse train paradigms we compared electrically evoked compound action potentials (eCAPs) in normal-hearing animals with those in animals with moderate (two weeks after ototoxic treatment) and severe (six weeks after ototoxic treatment) loss of spiral ganglion cells (SGCs). Masker-probe interval and pulse train inter-pulse interval was varied from 0.3 to 16 ms. Whereas recovery assessed with masker-probe was roughly similar for normal-hearing and both groups of deafened animals, it was considerably faster for six weeks deaf animals (τ ≈ 1.2 ms) than for two weeks deaf or normal-hearing animals (τ ≈ 3-4 ms) when 100-ms pulse trains were applied. Latency increased with decreasing inter-pulse intervals, and this was more pronounced with pulse trains than with masker-probe stimulation. With high frequency pulse train stimulation eCAP amplitudes were modulated for deafened animals, meaning that amplitudes for odd pulse numbers were larger than for even pulses. The relative refractory period (τ) and the modulation depth of the eCAP amplitude for pulse trains, as well as the latency increase for both paradigms significantly correlated with quantified measures of auditory nerve degeneration (size and packing density of SGCs). In addition to these findings, separate masker-probe recovery functions for the eCAP N1 and N2 peaks displayed a robust non-monotonic or shoulder-shaped course in all animals. The time interval between the N1 and N2 correlated with neuronal refractoriness, suggesting that the N2 peak reflects a second firing of part of the SGC population. We conclude that - compared to the commonly used masker-probe recovery functions - recovery functions obtained with pulse train stimulation may provide a means to augment differences and, by doing so, to more potently discriminate between auditory nerve conditions.
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: d.ramekers@umcutrecht.nl.
authors.forename: Dyan
authors.initials: D
authors.lastname: Ramekers
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: h.versnel@umcutrecht.nl.
authors.forename: Huib
authors.initials: H
authors.lastname: Versnel
authors.affiliation: Research and Development, MED-EL Medical Electronics, Fürstenweg 77a, 6020 Innsbruck, Austria. Electronic address: stefan.strahl@medel.com.
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Strahl
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: s.klis@umcutrecht.nl.
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: w.grolman@umcutrecht.nl.
authors.forename: Wilko
authors.initials: W
authors.lastname: Grolman
mesh_terms: D000818:Animals; D001307:Auditory Perception; D019929:Cochlear Implantation; D003056:Cochlear Nerve / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005072:Evoked Potentials, Auditory; D005260:Female; D005665:Furosemide; D006168:Guinea Pigs; D006309:Hearing; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007612:Kanamycin; D009410:Nerve Degeneration; D010470:Perceptual Masking; D011930:Reaction Time; D020127:Recovery of Function; D012032:Refractory Period, Electrophysiological; D013136:Spiral Ganglion / Q000503:physiopathology; D013997:Time Factors
chemical_list: D007612:Kanamycin; D005665:Furosemide