Cochlear Implant Research and Development in the Twenty-first Century: A Critical Update.

Cochlear implants (CIs) are the world's most successful sensory prosthesis and have been the subject of intense research and development in recent decades. We critically review the progress in CI research, and its success in improving patient outcomes, from the turn of the century to the present day. The review focuses on the processing, stimulation, and audiological methods that have been used to try to improve speech perception by human CI listeners, and on fundamental new insights in the response of the auditory system to electrical stimulation. The introduction of directional microphones and of new noise reduction and pre-processing algorithms has produced robust and sometimes substantial improvements. Novel speech-processing algorithms, the use of current-focusing methods, and individualised (patient-by-patient) deactivation of subsets of electrodes have produced more modest improvements. We argue that incremental advances have and will continue to be made, that collectively these may substantially improve patient outcomes, but that the modest size of each individual advance will require greater attention to experimental design and power. We also briefly discuss the potential and limitations of promising technologies that are currently being developed in animal models, and suggest strategies for researchers to collectively maximise the potential of CIs to improve hearing in a wide range of listening situations.

Bilateral cochlear implantation.

Binaural hearing has certain benefits while listening in noisy environments. It provides the listeners with access to time, level and spectral differences between sound signals, perceived by the two ears. However, single sided deaf (SSD) or unilateral cochlear implant (CI) users cannot experience these binaural benefits due to the acoustic input coming from a single ear. The translational research on bilateral CIs started in the year 1998, initiated by J. Müller and J. Helms from Würzburg, Germany in association with MED-EL. Since then, several clinical studies were conducted by different research groups from across the world either independently or in collaboration with MED-EL. As a result, the bilateral CI has become the standard of care in many countries along with reimbursement by the health care systems. Recent data shows that children particularly, are given high priority for the bilateral CI implantation, most often performed simultaneously in a single surgery, as the binaural hearing has a positive effect on their language development. This article covers the milestones of translational research from the first concept to the widespread clinical use of bilateral CI.

Special electrodes for demanding cochlear conditions.

Optimal matching of an electrode array to the cochlear anatomy plays a key role in bringing the best benefit of CI technology to the users. Even within the category of normal anatomy cochlea, the size variation is huge justifying MED-EL's FLEX electrode array to be available in five different lengths. Within the malformed inner-ear category the anatomical variation is huge, convincing MED-EL to custom-design the electrode array as per the request from the operating surgeons. Thanks to G. Bredberg, M. Beltrame, L. Sennaroglu, J. Gavilan, S. Plontke, T. Lenarz, J. Müller, and few others for their valuable suggestions on unique electrode designs satisfying various needs. Translational research efforts at MED-EL in cooperation with CI surgeons from across the world led to the implantation of a variety of electrode array designs in patients with special cochlear needs.

CI in single-sided deafness.

The cochlear implant (CI) as a treatment option for single-sided deafness (SSD) started with a clinical study looking in to the influence of cochlear implantation with a MED-EL device on incapacitating unilateral tinnitus in SSD. The study began in 2003 and was conducted by P. Van de Heyning and his team in Antwerp, Belgium. The first CI in SSD without tinnitus in Germany was implanted by J. Mueller and R. Jacob in Koblenz in 2005. Translational research activities took place since then to evaluate the CI as a treatment option for SSD not only in adults but also in children. They assessed the hearing performance of SSD patients implanted with CI, importance of long electrode arrays in SSD patients, degree of acceptance of CI by SSD children, importance of early CI implantation in SSD children in developing language skills, music enjoyment by hearing with two ears and evidence on spiral ganglion cell body distribution. In 2013, MED-EL was the first CI manufacturer to receive the CE mark for the indication of SSD and asymmetric hearing loss (AHL) in adults and children. In 2019, MED-EL was the first CI manufacturer to get its CI device approved for patients over the age of five with SSD and AHL, by the FDA in the USA. This article covers the milestones of translational research from the first concept to the widespread clinical use of CI in SSD.

EAS-Combined electric and acoustic stimulation.

Electric-acoustic stimulation (EAS) is a special treatment modality for those patients who are profoundly deaf in the high-frequency (HF) region and retain usable hearing in the low-frequency (LF) region. Combining the electric stimulation with cochlear implant (CI) in the HF and acoustic amplification of residual hearing using a conventional hearing aid (HA) in the LF region defines EAS. The EAS concept was first proposed by C. von Ilberg from Frankfurt, Germany in the year 1997. In association with MED-EL, all the necessary safety studies were performed in non-human subjects before the first patient received it in 1997. In association with MED-EL, all the necessary safety studies were performed in non-human subjects before the first patient received it in 1999. For the patient to successfully use the EAS concept, the residual hearing needs to be preserved to a high extent and for several years. This requires a highly flexible electrode array in safeguarding the intra-cochlear structures during and after the CI electrode array insertion. Combining the HA unit with the audio processor unit of the CI was necessary for the convenient wearing of the unified audio processor. Fitting of the unified audio processor is another important factor that contributes to the overall success of the EAS treatment. The key translational research efforts at MED-EL were on the development of flexible electrodes, a unified audio processor, innovations in the fitting process, intra-operative monitoring of cochlear health during electrode insertion, pre-operative soft-ware tool to evaluate the cochlear size and electrode selection and some new innovations tried within EAS topic. This article covers the milestones of translational research from the first concept to the widespread clinical use of EAS.

Signal processing & audio processors.

Signal processing algorithms are the hidden components in the audio processor that converts the received acoustic signal into electrical impulses while maintaining as much relevant information as possible. Signal processing algorithms should be smart enough to mimic the functionality of external, middle and the inner-ear to provide the cochlear implant (CI) user with a hearing experience as natural as possible. Modern sound processing strategies are based on the continuous interleaved sampling (CIS) strategy proposed by B. Wilson in 1991, which provided envelope information over several intracochlear electrodes. The CIS strategy brought significant gains in speech perception. Translational research activities of MED-EL resulted in further improvements in speech understanding in noisy environments as well as enjoyment of music by not only coding CIS-based envelope information, but by also representing temporal fine structure information in the stimulation patterns of the apical channels. Further developments include "complete cochlear coverage" made possible by deep insertion of the intracochlear electrode, elaborate front end processing, anatomy based fitting (ABF), triphasic pulse stimulation instrumental in the suppression of facial nerve stimulation, and bimodal delay compensation allowing unilateral CI users to experience hearing with hearing aids on the contralateral ear. The large number of hardware developments might be exemplified by the RONDO, the world's first single unit audio processor in 2013. This article covers the milestones of translational research around the signal processing and audio processor topic that took place in association with MED-EL.

Drug delivery in cochlear implantation.

Intra-cochlear fibrous tissue formation around the electrode following cochlear implantation affects the electrode impedance as well as electrode explantation during reimplantation surgeries. Applying corticosteroids in cochlear implantation is one way of minimizing the intra-cochlear fibrous tissue formation around the electrode. It were J. Kiefer, C. von Ilberg, and W. Gstöttner who proposed the first idea on drug delivery application in cochlear implantation to MED-EL in the year 2000. During the twenty years of translational research efforts at MED-EL in collaboration with several clinics and research institutions from across the world, preclinical safety and efficacy of corticosteroids were performed leading to the final formulation of the electrode design. In parallel to the drug eluting CI electrode development, MED-EL also invested research efforts into developing tools enabling delivery of pharmaceutical agents of surgeon's choice inside the cochlea. The inner ear catheter designed to administer drug substances into the cochlea was CE marked in 2020. A feasibility study in human subjects with MED-EL CI featuring dexamethasone-eluting electrode array started in June 2020. This article covers the milestones of translational research towards the drug delivery in CI application that took place in association with MED-EL.

Pediatric cochlear implantation: A quarter century in review.

Objective: To review the growth of a pediatric cochlear implant (CI) program at one large tertiary care medical center over a 25-year period in order to (1) describe the population of pediatric cochlear implant recipients, (2) document word recognition outcomes, and (3) describe changes in candidacy criteria over time. Design: A retrospective review of population demographics and trends included etiology of hearing loss, device use and type, expansion of inclusion criteria, and word recognition outcomes. Results: Ninety-one percent of the children studied were from North Carolina and reflect the ethnic distribution of the state. The population is heterogeneous for etiology and the presence of syndromes and/or co-morbidities. A trend of lower age of implant and greater residual hearing was documented overtime. As a single metric, monosyllable word recognition for the children assessed is good with the mean CNC test word score of 76.13% (range 0-100, S.D = 19.94). Conclusions: Pediatric cochlear implant candidacy criteria have evolved despite no change in FDA-approved regulations since 2000. There is great diversity among recipients but word recognition outcomes are generally good in this population and have improved over time. Professionals who may refer children for cochlear implantation should be aware of current clinical practices and general outcomes.

On the Horizon: Cochlear Implant Technology.

Cochlear implantation and cochlear implants (CIs) have a long history filled with innovations that have resulted in the high-performing device's currently available. Several promising technologies have been reviewed in this article, which hold the promise to drive performance even higher. Remote CI programming, totally implanted devices, improved neural health and survival through targeted drug therapy and delivery, intraneural electrode placement, electroacoustical stimulation and hybrid CIs, and methods to enhance the neural-prosthesis interface are evolving areas of innovation reviewed in this article.

The role of the Utah Artificial Ear project in the development of the modern cochlear implant.

The cochlear implant has provided the first substantial restoration of a human sense by a medical intervention. This accomplishment was brought about by the efforts, over a 50+ year period, of many individuals in laboratories around the world. In this paper, we recount the history of one of the early projects - the Utah Artificial Ear project. In 1970 researchers at the University of Utah began work on an auditory prosthesis. A critical early decision was to create a 'transparent' link between external signal processing and the electrodes implanted in the cochlea, i.e., a percutaneous pedestal. The pedestal allowed D. Eddington, then a graduate student, to conduct, in 1975-1978, the first thorough, parametric, psychophysical studies of electrical stimulation of the cochlea in multiple human volunteers. The early work by Eddington and colleagues evolved in 1983 into the 4-channel, Ineraid cochlear implant. Many years later, highly effective, modern signal processing algorithms, e.g., continuous interleaved sampling (CIS), fine structure processing (FSP), and virtual channel processing, were first tested and developed with the aid of Ineraid patients fit with pedestals of the Utah design. Because for many years the Ineraid provided as high a level of speech understanding as that provided by other devices and because the percutaneous pedestal allowed the first testing of many modern signal processing algorithms, the Utah Artificial Ear project may be viewed as one of the most valuable research projects in the history of cochlear implants.