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. 2014 Aug;11(4):046008.
doi: 10.1088/1741-2560/11/4/046008. Epub 2014 Jun 12.

A partial hearing animal model for chronic electro-acoustic stimulation

S Irving  1 , A K Wise, R E Millard, R K Shepherd, J B Fallon
Affiliations

A partial hearing animal model for chronic electro-acoustic stimulation

S Irving et al. J Neural Eng. 2014 Aug.

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 paper outlines such a model that has been successfully used in our laboratory.

Approach: This paper 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 results: 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.

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Figures

Figure 1
Figure 1
(A) Typical hearing ranges for hearing aid (HA), electro-acoustic (EAS) and cochlear implant only (CI) candidates. Adapted from Von Ilberg, Baumann et al. (2011). EAS recipients have significant hearing loss in higher frequencies. (B) Ototoxic deafening caused a bilaterally-symmetrical frequency-specific hearing loss (determined by ABR) in both neonatally- (n = 21) and adult-deafened (n = 10) animals. This loss is comparable to that seen in the clinical population seen in (A) for the frequency ranges available for each species. Lower frequencies had significantly greater hearing loss in the neonatal group compared to adults, although hearing remained within the boundaries of clinical normal hearing (horizontal dotted line).
Figure 2
Figure 2
Midmodiolar section of an adult-deafened organ of Corti labelled for Myosin (red) and Neurofilament (green) and DAPI (blue). (A) Apical organ of Corti showing an IHC (in red, grey arrow), three OHCs (white arrowheads) and extensive nerve fibers (star). (B) Organ of Corti from the upper basal turn showing partial degeneration – no hair cells are present, but the nerve fibers remain (green, star). (C) Basilar membrane from the lower basal turn. The organ of Corti has entirely degenerated, as evidenced by a flattened sensory epithelium and lack of innervation. Duration of deafness = 13 months. (D–F). Organ of Corti of a normal-hearing control, taken from similar cochlear positions as A–C (respectively). Inner and outer hair cells are intact and fully innervated. Scale bar = 50 μm.
Figure 3
Figure 3
ABR thresholds plotted against CAP threshold for adult deafened animals (n = 10). Dotted line is the line of equality. Marker shades indicate the stimulus frequency. Error bars indicate standard error of mean (s.e.m.). Inset: representative example of ABR (left) and CAP recorded using the NRT® system (right) in response to a 2 kHz pure tone, note different scales. The acoustic thresholds were the same (65 dB SPL).
Figure 4
Figure 4
Mean EABR thresholds plotted against mean ECAP thresholds in adult-deafened animals. Dotted line indicates the line of equality. Thresholds were not significantly different between the two measures, but varied with stimulating electrode indicating that ECAP and EABR provide comparable results. Inset: representative example of EABR (left) in response to stimulation from electrode 14; and ECAP in response to stimulation from electrode 2, recorded using the NRT® system (right). Note different scales. Error bars indicate standard error of the mean.
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