Deaf animal models for studies of a multichannel cochlear prosthesis

doi:10.1016/0378-5955(82)90076-4

Hearing Research

Volume 8, Issue 2, October 1982, Pages 225-246

https://doi.org/10.1016/0378-5955(82)90076-4 Get rights and content

Abstract

Pathological alterations of the cochlea were studied in three different deaf animal (cat) populations. The ototoxic drug neomycin sulfate, was administered in one experimental series by direct infusion into the cochlear perilymph; a second group was given a series of intramuscular injections of the drug; and in a third experiment a mechanical lesion was made in the basilar membrane of the basal turn and the animals subsequently deafened by systemic neomycin. Hearing losses were tracked by monitoring thresholds of auditory brainstem responses to click stimulation. These deaf cat preparations fairly efficiently model pathologies recorded in man and are highly predictable over an acceptable time frame. Such preparations are of practical value for experiments involving intracochlear electrical stimulation (e.g., with model cochlear prosthesis electrodes).

References (20)

S.M. Walsh et al.
Chronic electrical stimulation of auditory nerve in cat: Physiological and histological results
Hearing Res.
(1982)
B.A. Bohne
Safe level for noise exposure
Ann. Otol.
(1976)
J.E. Hawkins et al.
The patar monkey as a model for dihydrostreptomycin ototoxicity
Acta Otolaryngol.
(1977)
Y. Kaneko et al.
Single-cell membrane covering the degenerated cochlear duct after perilymphatic perfusion of streptomycin
Acta Otolaryngol.
(1978)
N.Y.-S. Kiang et al.
Physiological considerations in artificial stimulation of the inner ear
Ann. Otol.
(1972)
A. Kohenen
Effect of some ototoxic drugs upon the pattern and innervation of cochlear sensory cells in the guinea pig
Acta Otolaryngol.
(1965)
P.A. Leake-Jones et al.
Cochlear pathology following chronic intracochlear electrical stimulation
Ann. Otol.
(1981)
P.A. Leake-Jones et al.
Cochlear pathology in cats following administration of neomycin sulfate
P.A. Leake-Jones et al.
Neomycin ototoxicity: Ultrastructural surface pathology of the organ of Corti
E.C. Moxon
Neural and mechanical responses to electrical stimulation of the cat's inner ear

There are more references available in the full text version of this article.

Cited by (48)

Intracochlear near infrared stimulation: Feasibility of optoacoustic stimulation in vivo
2019, Hearing Research
Citation Excerpt :
Acute deafening by intra-scalar infusion of neomycin sulfate solution (2.5–5%) abolished all responses to acoustic stimulation, within minutes after infusion (compare Snyder et al., 2004; Middlebrooks and Bierer, 2002; Miller, 2001; Leake-Jones et al., 1982). In the current study, neomycin infusion was performed at the end of the experiments, with approximately 2 h of recordings after deafening, sufficient for data collection but too brief for allowing functional effects of neomycin on SGNs (Leake-Jones et al., 1982). Supporting this, electric stimulation at current levels that were in a typical range for acutely pharmacologically deafened guinea pigs (Sato et al., 2016; Snyder et al., 2004, 2008; Miller et al., 1993, 1998) resulted in the expected responses and confirmed the good function of the auditory nerve.
Intracochlear optical stimulation has been suggested as an alternative approach to hearing prosthetics in recent years. This study investigated the properties of a near infrared laser (NIR) induced optoacoustic effect. Pressure recordings were performed at the external meatus of anaesthetized guinea pigs during intracochlear NIR stimulation. The sound pressure and power spectra were determined. The results were compared to multi unit responses in the inferior colliculus (IC). Additionally, the responses to NIR stimulation were compared to IC responses induced by intracochlear electric stimulation at the same cochlear position to investigate a potentially confounding contribution of direct neural NIR stimulation. The power spectra of the sound recorded at the external meatus (n = 7) had most power at frequencies below 10 kHz and showed little variation for different stimulation sites. The mean spike rates of IC units responding to intracochlear NIR stimulation (n = 222) of 17 animals were significantly correlated with the power of the externally recorded signal at frequencies corresponding to the best frequencies of the IC units. The response strength as well as the sound pressure at the external meatus depended on the pulse peak power of the optical stimulus. The sound pressure recorded at the external meatus reached levels above 70 dB SPL peak equivalent. In hearing animals a cochlear activation apical to the location of the fiber was found. The absence of any NIR responses after pharmacologically deafening and the comparison to electric stimulation at the NIR stimulation site revealed no indication of a confounding direct neural NIR stimulation. Intracochlear optoacoustic stimulation might become useful in combined electro-acoustic stimulation devices in the future.
Cochlear implant electrode configuration effects on activation threshold and tonotopic selectivity
2008, Hearing Research
The multichannel design of contemporary cochlear implants (CIs) is predicated on the assumption that each channel activates a relatively restricted and independent sector of the deaf auditory nerve array, just as a sound within a restricted frequency band activates a restricted region of the normal cochlea The independence of CI channels, however, is limited; and the factors that determine their independence, the relative overlap of the activity patterns that they evoke, are poorly understood. In this study, we evaluate the spread of activity evoked by cochlear implant channels by monitoring activity at 16 sites along the tonotopic axis of the guinea pig inferior colliculus (IC). “Spatial tuning curves” (STCs) measured in this way serve as an estimate of activation spread within the cochlea and the ascending auditory pathways. We contrast natural stimulation using acoustic tones with two kinds of electrical stimulation either (1) a loose fitting banded array consisting of a cylindrical silicone elastomer carrier with a linear series of ring contacts; or (2) a space-filling array consisting of a tapered silicone elastomer carrier that is designed to fit snugly into the guinea pig scala tympani with a linear series of ball contacts positioned along it Spatial tuning curves evoked by individual acoustic tones, and by activation of each contact of each array as a monopole, bipole or tripole were recorded. Several channel configurations and a wide range of electrode separations were tested for each array, and their thresholds and selectivity were estimated.
The results indicate that the tapered space-filling arrays evoked more restricted activity patterns at lower thresholds than did the banded arrays. Monopolar stimulation (one intracochlear contact activated with an extracochlear return) using either array evoked broad activation patterns that involved the entire recording array at current levels <6 dB SL, but at relatively low thresholds. Bi- and tri-polar configurations of both array types evoked more restricted activity patterns, but their thresholds were higher than those of monopolar configurations. Bipolar and tripolar configurations with closely spaced contacts evoked activity patterns that were comparable to those evoked by pure tones. As the spacing of bipolar electrodes was increased (separations >1 mm), the activity patterns became broader and evoked patterns with two distinct threshold minima, one associated with each contact.
Acoustic-electric interactions in the guinea pig auditory nerve: Simultaneous and forward masking of the electrically evoked compound action potential
2007, Hearing Research
The study investigated the time course of the effects of acoustic and electric stimulation on the electrically evoked compound action potential (ECAP). Adult guinea pigs were used in acute experimental sessions. Bursts of acoustic noise and high-rate (5000 pulses/s) electric pulse trains were used as maskers. Biphasic electric pulses were used as probes. ECAPs were recorded from the auditory nerve trunk.
Simultaneous masking of the ECAP with acoustic noise featured an onset effect and a decrease in the amount of masking to a steady state. It was characterized by a two-component exponential function. The amount of masking increased with masker level and decreased with probe level. Post-stimulatory ECAP recovery often featured a non-monotonic time course, described by a three-component exponent. Electric maskers produced similar post-stimulatory effects in hearing and acutely deafened subjects.
Acoustic stimulation affects the ECAP in a level- and time-dependent manner. Simultaneous masking follows a time course comparable to that of adaptation to an acoustic stimulus. Refractoriness, spontaneous activity, and adaptation are suggested to play a role in ECAP recovery. Post-stimulatory changes in synchrony, possibly due to recovery of spontaneous activity and an additional hair-cell independent mechanism, are hypothesized to contribute to the observed non-monotonicity of recovery.
Chapter 18 Cochlear implants: cortical plasticity in congenital deprivation
2006, Progress in Brain Research
Citation Excerpt :
In neonatally deafened animals, the destruction of the inner ear is achieved by systemic application of ototoxic substances during the phase of hearing acquisition. The advantage of neonatally deafened animals is the easy availability, and the disadvantage is the pronounced and rapid degeneration of spiral ganglion cells (cell loss from 50–90% of normal counts after several weeks to months of deafness, see Leake-Jones et al., 1982; Leake et al., 1987, 1999; Leake and Hradek, 1988; Dodson, 1997a, b, 2000). It is an important advantage of congenitally deaf strains that some of them show a slow degeneration of spiral ganglion cells, comparable to human congenital deafness.
Congenital auditory deprivation (deafness) leads to a dysfunctional intrinsic cortical microcircuitry. This chapter reviews these deficits with a particular emphasis on layer-specific activity within the primary auditory cortex. Evidence for a delay in activation of supragranular layers and reduction in activity in infragranular layers is discussed. Such deficits indicate the incompetence of the primary auditory cortex to not only properly process thalamic input and generate output within the infragranular layers, but also incorporate top-down modulations from higher order auditory cortex into the processing within primary auditory cortex. Such deficits are the consequence of a misguided postnatal development. Maturation of primary auditory cortex in deaf animals shows evidence of a developmental delay and further alterations in gross synaptic currents, spread of activation, and morphology of local field potentials recorded at the cortical surface. Additionally, degenerative changes can be observed. When hearing is initiated early in life (e.g., by chronic cochlear-implant stimulation), many of these deficits are counterbalanced. However, plasticity of the auditory cortex decreases with increasing age, so that a sensitive period for plastic adaptation can be demonstrated within the second to sixth months of life in the deaf cat. Potential molecular mechanisms of the existence of sensitive period are discussed. Data from animal research may be compared to electroencephalographic data obtained from cochlear-implanted congenitally deaf children. After cochlear implantation in humans, three phases of plastic adaptation can be observed: a fast one, taking place within the first few weeks after implantation, showing no sensitive period; a slower one, taking place within the first months after implantation (a sensitive period up to 4 years of age); and possibly a third, and the longest one, related to increasing activation of higher order cortical areas.
Co-administration of kanamycin and ethacrynic acid as a deafening method for acute animal experiments
2004, Hearing Research
Auditory response to intracochlear electric stimuli following furosemide treatment
2003, Hearing Research
The influence of functional hair cells on electrical stimulation of the auditory nerve is an important issue as individuals with significant residual hearing are now cochlear implant candidates. Previous work has shown that chemical deafening during the course of acute experiments changes the auditory nerve’s responses to electrical stimulation [Third Quarterly Progress Report, NIH contract N01-DC-9-2106 (2000), Final Report, NIH Contract N01-DC-9-2106 (2002)]. This study extended that work by investigating the changes and subsequent recovery following furosemide injections which reversibly impair hair-cell function [Hear. Res. (1980) 79–89; Hear. Res. 14 (1984) 305–314, J. Physiol. 347 (1984) 685–696; Hear. Res. 71 (1993) 202–207]. Acoustic sensitivity of guinea pig subjects was repeatedly monitored with the click-evoked compound action potential. Responses to single biphasic electric pulses and biphasic electric pulse trains delivered by a monopolar intracochlear electrode were also repeatedly assessed using the electrically evoked compound action potential (ECAP). Our measures demonstrated a clear relationship between the state of hair-cell function and ECAP responses, as changes in the latter coincided with the loss or recovery of acoustic sensitivity. ECAP growth functions demonstrated increased slope and increased maximum (saturation) amplitude. Both trends were reversible and followed approximately the time course of post-furosemide hearing recovery. Additional changes were observed using electric pulse-train stimulation: (1) the magnitude of ECAP amplitude alternation (observed in response to successive stimulus pulses) increased, (2) the degree of ECAP adaptation (measured 80–100 ms after pulse-train onset) increased, and (3) the degree of refractoriness (measured by the ratio of ECAP amplitudes to the second and first pulses) tended to increase. All these trends are consistent with the hypothesis that functional hair cells desynchronize the population of auditory nerve fibers, thereby changing the electrically evoked responses. Viable hair cells may therefore provide positive effects on auditory response to electric stimuli delivered to implant patients with residual hearing, as they may enhance the random activity of the stimulated nerve.

View all citing articles on Scopus

View full text

Deaf animal models for studies of a multichannel cochlear prosthesis

Abstract

Hearing Res.

Safe level for noise exposure

Ann. Otol.

The patar monkey as a model for dihydrostreptomycin ototoxicity

Acta Otolaryngol.

Single-cell membrane covering the degenerated cochlear duct after perilymphatic perfusion of streptomycin

Acta Otolaryngol.

Physiological considerations in artificial stimulation of the inner ear

Ann. Otol.

Effect of some ototoxic drugs upon the pattern and innervation of cochlear sensory cells in the guinea pig

Acta Otolaryngol.

Cochlear pathology following chronic intracochlear electrical stimulation

Ann. Otol.

Cochlear pathology in cats following administration of neomycin sulfate

Neomycin ototoxicity: Ultrastructural surface pathology of the organ of Corti

Neural and mechanical responses to electrical stimulation of the cat's inner ear