Abstract
Fibrous tissue and/or new bone are often found surrounding a cochlear implant in the cochlear scalae. This new intrascalar tissue could potentially limit cochlear implant function by increasing impedance and altering signaling pathways between the implant and the auditory nerve. In this study, we investigated the relationship between intrascalar tissue and 5 measures of implant function in guinea pigs. Variation in both spiral ganglion neuron (SGN) survival and intrascalar tissue was produced by implanting hearing ears, ears deafened with neomycin, and neomycin-deafened ears treated with a neurotrophin. We found significant effects of SGN density on 4 functional measures but adding intrascalar tissue level to the analysis did not explain more variation in any measure than was explained by SGN density alone. These results suggest that effects of intrascalar tissue on electrical hearing are relatively unimportant in comparison to degeneration of the auditory nerve, although additional studies in human implant recipients are still needed to assess the effects of this tissue on complex hearing tasks like speech perception. The results also suggest that efforts to minimize the trauma that aggravates both tissue development and SGN loss could be beneficial.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bas E, Dinh CT, Garnham C, Polak M, Van de Water TR (2012a) Conservation of hearing and protection of hair cells in cochlear implant patients' with residual hearing. Anat Rec 295:1909–1927. https://doi.org/10.1002/ar.22574
Bas E, Gupta C, Van De Water TR (2012b) A novel organ of Corti explant model for the study of cochlear implantation trauma. Anat Rec 295:1944–1956. https://doi.org/10.1002/ar.22585
Bas E, Goncalves S, Adams M, Dinh CT, Bas JM, Van De Water TR, Eshraghi AA (2015) Spiral ganglion cells and macrophages initiate neuro-inflammation and scarring following cochlear implantation. Front Cell Neurosci 9:16. https://doi.org/10.3389/fncel.2015.00303
Blamey PJ, Pyman BC, Clark GM, Dowell RC, Gordon M, Brown AM, Hollow RD (1992) Factors predicting postoperative sentence scores in postlinguistically deaf adult cochlear implant patients. Ann Otol Rhinol Laryngol 101:342–348. https://doi.org/10.1177/000348949210100410
Borg E, Engstrom B, Linde G, Marklund K (1988) 8th nerve-fiber firing features in normal-hearing rabbits. Hear Res 36:191–201. https://doi.org/10.1016/0378-5955(88)90061-5
Budenz CL, Cosetti MK, Coelho DH, Birenbaum B, Babb J, Waltzman SB, Roehm PC (2011) The effects of cochlear implantation on speech perception in older adults. J Am Geriatr Soc 59:446–453. https://doi.org/10.1111/j.1532-5415.2010.03310.x
Burghard A, Lenarz T, Kral A, Paasche G (2014) Insertion site and sealing technique affect residual hearing and tissue formation after cochlear implantation. Hear Res 312:21–27. https://doi.org/10.1016/j.heares.2014.02.002
Chen HC, Xing YZ, Xia L, Chen ZN, Yin SK, Wang J (2018) AAV-mediated NT-3 overexpression protects cochleae against noise-induced synaptopathy. Gene Ther 25:251–259. https://doi.org/10.1038/s41434-018-0012-0
Choi CH, Oghalai JS (2005) Predicting the effect of post-implant cochlear fibrosis on residual hearing. Hear Res 205:193–200. https://doi.org/10.1016/j.heares.2005.03.018
Clark GM, Tong YC, Patrick JF, Seligman PM, Crosby PA, Kuzma JA, Money DK (1984) A multi-channel hearing prosthesis for profound-to-total hearing-loss. J Med Eng Technol 8:3–8. https://doi.org/10.3109/03091908409032065
Côté M, Ferron P, Bergeron F, Bussières R (2007) Cochlear reimplantation: causes of failure, outcomes, and audiologic performance. Laryngoscope 117:1225–1235. https://doi.org/10.1097/MLG.0b013e31805c9a06
Crozier RA, Davis RL (2014) Unmasking of spiral ganglion neuron firing dynamics by membrane potential and neurotrophin-3. J Neurosci 34:9688–9702. https://doi.org/10.1523/jneurosci.4552-13.2014
Eshraghi AA, Yang NW, Balkany TJ (2003) Comparative study of cochlear damage with three perimodiolar electrode designs. Laryngoscope 113:415–419. https://doi.org/10.1097/00005537-200303000-00005
Eshraghi AA, Gupta C, Van de Water TR, Bohorquez JE, Garnham C, Bas E, Talamo VM (2013) Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-n-terminal kinase signaling. Laryngoscope 123:S1–S14. https://doi.org/10.1002/lary.23902
Fayad JN, Linthicum FH (2006) Multichannel cochlear implants: relation of histopathology to performance. Laryngoscope 116:1310–1320. https://doi.org/10.1097/01.mlg.0000227176.09500.28
Fayad JN, Makarem AO, Linthicum FH (2009) Histopathologic assessment of fibrosis and new bone formation in implanted human temporal bones using 3d reconstruction. Otolaryngol Head Neck Surg 141:247–252. https://doi.org/10.1016/j.otohns.2009.03.031
Fransson A, de Medina P, Paillasse MR, Silvente-Poirot S, Poirot M, Ulfendahl M (2015) Dendrogenin a and b two new steroidal alkaloids increasing neural responsiveness in the deafened Guinea pig. Front Aging Neurosci 7:7. https://doi.org/10.3389/fnagi.2015.00145
Gabriel S, Lau RW, Gabriel C (1996) The dielectric properties of biological tissues .2. Measurements in the frequency range 10 Hz to 20 GHz. Phys Med Biol 41:2251–2269. https://doi.org/10.1088/0031-9155/41/11/002
Garadat SN, Zwolan TA, Pfingst BE (2012) Across-site patterns of modulation detection: relation to speech recognition. J Acoust Soc Am 131:4030–4041. https://doi.org/10.1121/1.3701879
Geddes LA, Baker LE (1967) Specific resistance of biological material-a compendum of data for biomedical engineer and physiologist. Med Biol Eng 5:271–293. https://doi.org/10.1007/bf02474537
Green KMJ, Bhatt YM, Mawman DJ, O'Driscoll MP, Saeed SR, Ramsden RT, Green MW (2007) Predictors of audiological outcome following cochlear implantation in adults. Cochlear Implants International 8:1–11. https://doi.org/10.1179/cim.2007.8.1.1
Hashimoto K, Hickman TT, Suzuki J, Ji LC, Kohrman DC, Corfas G, Liberman MC (2019) Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3. Sci Rep 9:12. https://doi.org/10.1038/s41598-019-51724-6
Heydebrand G, Hale S, Potts L, Gotter B, Skinner M (2007) Cognitive predictors of improvements in adults' spoken word recognition six months after cochlear implant activation. Audiol Neuro-Otol 12:254–264. https://doi.org/10.1159/000101473
Hochmair ES, Hochmair-Desoyer IJ (1981) An implanted auditory 8-channel stimulator for the deaf. Med Biol Eng Comput 19:141–148. https://doi.org/10.1007/BF02442707
Holden LK, Finley CC, Firszt JB, Holden TA, Brenner C, Potts LG, Gotter BD, Vanderhoof SS, Mispagel K, Heydebrand G, Skinner MW (2013) Factors affecting open-set word recognition in adults with cochlear implants. Ear Hear 34:342–360. https://doi.org/10.1097/AUD.0b013e3182741aa7
Honeder C, Landegger LD, Engleder E, Gabor F, Plasenzotti R, Plenk H, Kaider A, Hirtler L, Gstoettner W, Arnoldner C (2015) Effects of intraoperatively applied glucocorticoid hydrogels on residual hearing and foreign body reaction in a guinea pig model of cochlear implantation. Acta Otolaryngol 135:313–319. https://doi.org/10.3109/00016489.2014.986758
Inaoka T, Shintaku H, Nakagawa T, Kawano S, Ogita H, Sakamoto T, Hamanishi S, Wada H, Ito J (2011) Piezoelectric materials mimic the function of the cochlear sensory epithelium. Proc Natl Acad Sci 108:18390–18395. https://doi.org/10.1073/pnas.1110036108
Ishai R, Herrmann BS, Nadol JB, Quesnel AM (2017) The pattern and degree of capsular fibrous sheaths surrounding cochlear electrode arrays. Hear Res 348:44–53. https://doi.org/10.1016/j.heares.2017.02.012
Izumikawa M, Minoda R, Kawamoto K, Abrashkin KA, Swiderski DL, Dolan DF, Brough DE, Raphael Y (2005) Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat Med 11:271–276. https://doi.org/10.1038/nm1193
Jahn KN, Arenberg JG (2019) Evaluating psychophysical polarity sensitivity as an indirect estimate of neural status in cochlear implant listeners. J Assoc Res Otolaryngol 20:415–430. https://doi.org/10.1007/s10162-019-00718-2
Kamakura T, Nadol JB (2016) Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human. Hear Res 339:132–141. https://doi.org/10.1016/j.heares.2016.06.015
Kang SY, Colesa DJ, Swiderski DL, Su GL, Raphael Y, Pfingst BE (2010) Effects of hearing preservation on psychophysical responses to cochlear implant stimulation. J Assoc Res Otolaryngol 11:245–265. https://doi.org/10.1007/s10162-009-0194-7
Kanzaki S, Kawamoto K, Oh SH, Stover T, Suzuki M, Ishimoto S, Yagi M, Miller JM, Lomax MI, Raphael Y (2002) From gene identification to gene therapy. Audiol Neuro-Otol 7:161–164. https://doi.org/10.1159/000058303
Kaur T, Hirose K, Rubel EW, Warchol ME (2015a) Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle. Front Cell Neurosci 9:9. https://doi.org/10.3389/fncel.2015.00150
Kaur T, Zamani D, Tong L, Rubel EW, Ohlemiller KK, Hirose K, Warchol ME (2015b) Fractalkine signaling regulates macrophage recruitment into the cochlea and promotes the survival of spiral ganglion neurons after selective hair cell lesion. J Neurosci 35:15050–15061. https://doi.org/10.1523/jneurosci.2325-15.2015
Kawamoto K, Yagi M, Stover T, Kanzaki S, Raphael Y (2003) Hearing and hair cells are protected by adenoviral gene therapy with TGF-beta1 and GDNF. Mol Ther 7:484–492. https://doi.org/10.1016/S1525-0016(03)00058-3
Kel GE, Tan J, Eastwood HT, Wongprasartsuk S, O'Leary SJ (2013) Early cochlear response and ICAM-1 expression to cochlear implantation. Otol Neurotol 34:1595–1602. https://doi.org/10.1097/MAO.0b013e31828f4929
Khan AM, Handzel O, Burgess BJ, Damian D, Eddington DK, Nadol JB (2005) Is word recognition correlated with the number of surviving spiral ganglion cells and electrode insertion depth in human subjects with cochlear implants? Laryngoscope 115:672–677. https://doi.org/10.1097/01.mlg.0000161335.62139.80
Kiefer J, Bohnke F, Adunka O, Arnold W (2006) Representation of acoustic signals in the human cochlea in presence of a cochlear implant electrode. Hear Res 221:36–43. https://doi.org/10.1016/j.heares.2006.07.013
Knisely K, Zhao CM, Grosh K (2015) A MEMS AlN transducer array with flexible interconnections for use as a cochlear implant. In: Karavitaki KD and Corey DP.(eds.) mechanics of hearing: protein to perception. Amer Inst Physics, Melville. https://doi.org/10.1063/1.4939432
Li PMMC, Somdas MA, Eddington DK, Nadol JB (2007) Analysis of intracochlear new bone and fibrous tissue formation in human subjects with cochlear implants. Ann Otol Rhinol Laryngol 116:731–738. https://doi.org/10.1177/000348940711601004
Liu Y, Okada T, Shimazaki K, Sheykholeslami K, Nomoto T, Muramatsu S, Mizukami H, Kume A, Xiao S, Ichimura K, Ozawa K (2008) Protection against aminoglycoside-induced ototoxicity by regulated AAV vector-mediated GDNF gene transfer into the cochlea. Mol Ther 16:474–480. https://doi.org/10.1038/sj.mt.6300379
Moberly AC, Bates C, Harris MS, Pisoni DB (2016) The enigma of poor performance by adults with cochlear implants. Otol Neurotol 37:1522–1528. https://doi.org/10.1097/MAO.0000000000001211
O'Leary SJ, Monksfield P, Kel G, Connolly T, Souter MA, Chang A, Marovic P, O'Leary JS, Richardson R, Eastwood H (2013) Relations between cochlear histopathology and hearing loss in experimental cochlear implantation. Hear Res 298:27–35. https://doi.org/10.1016/j.heares.2013.01.012
Parkins CW (1985) The bionic ear - principles and current status of cochlear prostheses. Neurosurgery 16:853–865. https://doi.org/10.1227/00006123-198506000-00025
Pfingst BE, Colesa DJ, Hembrador S, Kang SY, Middlebrooks JC, Raphael Y, Su GL (2011) Detection of pulse trains in the electrically stimulated cochlea: effects of cochlear health. J Acoust Soc Am 130:3954–3968. https://doi.org/10.1121/1.3651820
Pfingst BE, Hughes AP, Colesa DJ, Watts MM, Strahl SB, Raphael Y (2015) Insertion trauma and recovery of function after cochlear implantation: evidence from objective functional measures. Hear Res 330:98–105. https://doi.org/10.1016/j.heares.2015.07/010
Pfingst BE, Colesa DJ, Swiderski DL, Hughes AP, Strahl SB, Sinan M, Raphael Y (2017) Neurotrophin gene therapy in deafened ears with cochlear implants: long-term effects on nerve survival and functional measures. J Assoc Res Otolaryngol 18:731–750. https://doi.org/10.1007/s10162-017-0633-9
Prado-Guitierrez P, Fewster LM, Heasman JM, Mckay CM, Shepherd RK (2006) Effect of interphase gap and pulse duration on electrically evoked potentials is correlated with auditory nerve survival. Hear Res 215:47–55. https://doi.org/10.1016/j.heares.2006.03.006
Quesnel AM, Nakajima HH, Rosowski JJ, Hansen MR, Gantz BJ, Nadol JB (2016) Delayed loss of hearing after hearing preservation cochlear implantation: human temporal bone pathology and implications for etiology. Hear Res 333:225–234. https://doi.org/10.1016/j.heares.2015.08.018
R Core Team (2018) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
Ramekers D, Versnel H, Strahl SB, Smeets EM, Klis SF, Grolman W (2014) Auditory-nerve responses to varied inter-phase gap and phase duration of the electric pulse stimulus as predictors for neuronal degeneration. J Assoc Res Otolaryngol 15:187–202. https://doi.org/10.1007/s10162-013-0440-x
Reis M, Boisvert I, Looi V, da Cruz M (2017) Speech recognition outcomes after cochlear reimplantation surgery. Trends Hear 21:9. https://doi.org/10.1177/2331216517706398
Richardson RT, Wise AK, Thompson BC, Flynn BO, Atkinson PJ, Fretwell NJ, Fallon JB, Wallace GG, Shepherd RK, Clark GM, O'Leary SJ (2009) Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons. Biomaterials 30:2614–2624. https://doi.org/10.1016/j.biomaterials.2009.01.015
Ryan AF, Harris JP, Keithley EM (2002) Immune-mediated hearing loss: basic mechanisms and options for therapy. Acta Oto-Laryngol 122 supplement 548:38–43. https://doi.org/10.1080/00016480260094965
Ryu KA, Lyu AR, Park H, Choi JW, Hur GM, Park YH (2015) Intracochlear bleeding enhances cochlear fibrosis and ossification: an animal study. PLoS One 10:13. https://doi.org/10.1371/journal.pone.0136617
Schvartz-Leyzac KC, Pfingst BE (2016) Across-site patterns of electrically evoked compound action potential amplitude-growth functions in multichannel cochlear implant recipients and the effects of the interphase gap. Hear Res 341:50–65. https://doi.org/10.1016/j.heares.2016.08.002
Schvartz-Leyzac KC, Pfingst BE (2018) Assessing the relationship between the electrically evoked compound action potential and speech recognition abilities in bilateral cochlear implant recipients. Ear Hear 39:344–358. https://doi.org/10.1097/AUD.0000000000000490
Schvartz-Leyzac KC, Holden TA, Zwolan TA, Arts HA, Firszt JB, Buswinka CJ, Pfingst BE (2020) Effects of electrode location on estimates of neural health in humans with cochlear implants. J Assoc Res Otolaryngol (early view). https://doi.org/10.1007/s10162-020-00749-0
Seyyedi M, Nadol JB Jr (2014) Intracochlear inflammatory response to cochlear implant electrodes in humans. Otol Neurotol 35:1545–1551. https://doi.org/10.1097/MAO.0000000000000540
Seyyedi M, Viana LM, Nadol JB (2014) Within-subject comparison of word recognition and spiral ganglion cell count in bilateral cochlear implant recipients. Otol Neurotol 35:1446–1450
Shepherd RK, Clark GM, Black RC, Patrick JF (1983) The histopathological effects of chronic electrical-stimulation of the cat cochlea. J Laryngol Otol 97:333–341. https://doi.org/10.1017/s0022215100094202
Shepherd RK, Hatsushika S, Clark GM (1993) Electrical-stimulation of the auditory-nerve - the effect of electrode position on neural excitation. Hear Res 66:108–120. https://doi.org/10.1016/0378-5955(93)90265-3
Shrestha BR, Chia C, Wu L, Kujawa SG, Liberman MC, Goodrich LV (2018) Sensory neuron diversity in the inner ear is shaped by activity. Cell 174:1229–1246. https://doi.org/10.1016/j.cell.2018.07.007
Sly DJ, Campbell L, Uschakov A, Saief ST, Lam M, O'Leary SJ (2016) Applying neurotrophins to the round window rescues auditory function and reduces inner hair cell synaptopathy after noise-induced hearing loss. Otol Neurotol 37:1223–1230. https://doi.org/10.1097/mao.0000000000001191
Souter M, Eastwood H, Marovic P, Kel G, Wongprasartsuk S, Ryan AF, O'Leary SJ (2012) Systemic immunity influences hearing preservation in cochlear implantation. Otol Neurotol 33:532–538. https://doi.org/10.1097/MAO.0b013e31824bac44
Spoendlin H (1984) Factors inducing retrograde degeneration of the cochlear nerve. Ann Otol Rhinol Laryngol 93:76–82
Suzuki M, Yagi M, Brown JN, Miller AL, Miller JM, Raphael Y (2000) Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity. Gene Ther 7:1046–1054. https://doi.org/10.1038/sj.gt.3301180
Suzuki J, Corfas G, Liberman MC (2016) Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure. Sci Rep 6:11. https://doi.org/10.1038/srep24907
Wang Q, Green SH (2011) Functional role of Neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro. J Neurosci 31:7938–7949. https://doi.org/10.1523/jneurosci.1434-10.2011
Wilk M, Hessler R, Mugridge K, Jolly C, Fehr M, Lenarz T, Scheper V (2016) Impedance changes and fibrous tissue growth after cochlear implantation are correlated and can be reduced using a dexamethasone eluting electrode. PLoS One 11:19. https://doi.org/10.1371/journal.pone.0147552
Yamahara K, Nishimura K, Ogita H, Ito J, Nakagawa T, Furuta I, Kita T, Omori K, Yamamoto N (2018) Hearing preservation at low frequencies by insulin-like growth factor 1 in a Guinea pig model of cochlear implantation. Hear Res 368:92–108. https://doi.org/10.1016/j.heares.2018.07.004
Ylikoski J, Wersäll J, Björkroth B (1974) Degeneration of neural elements in the cochlea of the guinea-pig after damage to the organ of Corti by ototoxic antibiotics. Acta Otolaryngol 78(suppl 326):23–41. https://doi.org/10.3109/00016487409129730
Zhang HZ, Stark G, Reiss L (2015) Changes in gene expression and hearing thresholds after cochlear implantation. Otol Neurotol 36:1157–1165. https://doi.org/10.1097/mao.0000000000000787
Zhao C, Knisely KE, Colesa DJ, Pfingst BE, Raphael Y, Grosh K (2019) Voltage readout from a piezoelectric intracochlear acoustic transducer implanted in a living guinea pig. Sci Rep 9:3711. https://doi.org/10.1038/s41598-019-39303-1
Zhou N, Pfingst BE (2014) Relationship between multipulse integration and speech recognition with cochlear implants. J Acoust Soc Am 136:1257–1268. https://doi.org/10.1121/1.4890640
Zwolan TA, Collins LM, Wakefield GH (1997) Electrode discrimination and speech recognition in postlingually deafened adult cochlear implant subjects. J Acoust Soc Am 102:3673–3685. https://doi.org/10.1121/1.420401
Acknowledgements
The authors thank Lisa Beyer and Laila Al-Jerdi for technical assistance. This work was supported by NIH NIDCD grants R01 DC010786 and R01 DC015809, and contracts from MED-EL.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Swiderski, D.L., Colesa, D.J., Hughes, A.P. et al. Relationships between Intrascalar Tissue, Neuron Survival, and Cochlear Implant Function. JARO 21, 337–352 (2020). https://doi.org/10.1007/s10162-020-00761-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10162-020-00761-4