A partial hearing animal model for chronic electro-acoustic stimulation

Abstract

Objective Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This manuscript outlines such a model that has been successfully used in our laboratory. Approach This manuscript outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main Result Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual hearing following cochlear implantation. The ability to record CAPs via the CI has clinical direct relevance for obtaining objective measures of residual hearing.

Cochlear Response Telemetry

“…The different components of the ECochG waveform are generated by different structures within the cochlea. A similar approach has been described in feline experimental cochlear implantation (18), using the standard NRT system, which has a recording window that is limited to 3-ms duration. Hair cell function can be inferred from cochlear microphonics (CM) and the summating potential (SP).…”

Evaluation of focused multipolar stimulation for cochlear implants: a preclinical safety study

“…Recordings were made at 10 CL (21 μA) intensity intervals from below threshold to a maximum of 250 CL (1,600 μA) or the highest level that did not produce an aversive response. ECAP thresholds and growth functions were examined longitudinally for evidence of changes in neural excitability during the course of chronic stimulation and compared statistically with responses recorded from the contralateral implanted/deafened control cochlea (Irving et al, 2014). ECAP threshold was defined as the lowest current amplitude required to elicit a clear ECAP with an amplitude of at least 20 μV.…”

Second spatial derivative analysis of cortical surface potentials recorded in cat primary auditory cortex using thin film surface arrays: Comparisons with multi-unit data

“…Hearing status was determined using auditory brainstem response (ABR) recordings using standard procedures (Irving et al, 2014), with normal hearing defined as a click-ABR threshold < 32 dB peak equivalent sound pressure level (SPL). All procedures were in accordance with Australian Code of Practice for the Care and Use of Animals for Scientific Purposes and with the Guidelines laid down by the National Institutes of Health in the US regarding the care and use of animals for experimental procedures, and were approved by the Royal Victorian Eye and Ear Hospital Animal Research and Ethics Committee.…”

“…Thirteen cats were administered a daily subcutaneous (s.c.) injection of kanamycin sulfate (200 mg/kg) for 17 days (Irving et al, 2014), which preferentially damages the high-frequency basal region of the cochlea. Tone-evoked ABRs were used to determine the degree of hearing loss achieved.…”

“…Briefly, surgery was performed under aseptic conditions, with each animal premedicated using atropine/acepromazine (ANAMAV, 0.05 ml/kg s.c.) and maintained at a surgical level of anesthesia using a closed circuit anesthetic machine delivering a mixture of isoflurane (1-3%) and oxygen. The array was inserted to approximately 50% the length of the cat scala tympani, representing a tip electrode position of around 4 kHz (Irving et al, 2014). …”