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.

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.

Feasibility of TMS in patients with new generation cochlear implants.

OBJECTIVE: The presence of a cochlear implant is being considered an absolute contraindication for experiments and/or treatments. We aimed to verify TMS (Transcranial Magnetic Stimulation) compatibility of a new generation of cochlear implants. METHODS: In a series of experiments, we test if MED-EL cochlear implants -compatible with stable fields of magnetic resonance imaging scanning- are fully resistant even to rapidly varying magnetic fields as those generated by single pulses and low and high-frequency trains of repetitive TMS (rTMS) applied with a figure of eight coil and different magnetic stimulators. RESULTS: With a TMS intensity equal or below 2.2 Tesla (T) the cochlear implant and all its electronic components remain fully functional, even when the combination of frequency, intensity and number of pulses exceeds the currently available safety guidelines. Induced forces on the implant are negligible. With higher magnetic fields (i.e., 3.2 T), one device was corrupted. CONCLUSIONS: Results exclude the risk of electronic damaging, demagnetizing or displacements of the studied cochlear implants when exposed to magnetic fields of up to 2.2 T delivered through a focal coil. SIGNIFICANCE: They open the way to use focal rTMS protocols with the aim of promoting neural plasticity in auditory networks, possibly helping the post-implant recovery of speech perception performance.

Global Regulatory Review Needed for Cochlear Implants: A Call for FDA Leadership.

INTRODUCTION: Using the United States Food and Drug Administration (FDA) as example, we argue that regulatory agencies worldwide should review their guidance on cochlear implants (CIs). METHODS: This is a position paper, thus the methods are strictly argumentation. Here we give the motivation for our recommendation. The FDA's original approval of implantation in prelingually deaf children was granted without full benefit of information on language acquisition, on childcaregiver communication, and on the lived experience of being deaf. The CI clinical trials, accordingly, did not address risks of linguistic deprivation, especially when the caregiver's communication is not fully accessible to the prelingually deaf child. Wide variability in the effectiveness of CIs since initial and updated approval has been indicated but has not led to new guidance. Children need to be exposed frequently and regularly to accessible natural language while their brains are still plastic enough to become fluent in any language. For the youngest infants, who are not yet producing anything that could be called language although they might be producing salient social signals (Goldstein et al. Child Dev 80:636-644, 2009), good comprehension of communication from caregiver to infant is critical to the development of language. Sign languages are accessible natural languages that, because they are visual, allow full immersion for deaf infants, and they supply the necessary support for this comprehension. The main language contributor to health outcomes is this combination of natural visual language and comprehension in communication. Accordingly, in order to prevent possible language deprivation, all prelingually deaf children should be exposed to both sign and spoken languages when their auditory status is detected, with sign language being critical during infancy and early childhood. Additionally, all caregivers should be given support to learn a sign language if it is new to them so that they can comprehend their deaf children's language expressions fully. However, both languages should be made accessible in their own right, not combined in a simultaneous or total communication approach since speaking one language and signing the other at the same time is problematic. RESULTS: Again, because this is a position paper, our results are our recommendations. We call for the FDA (and similar agencies in other countries) to review its approval of cochlear implantation in prelingually deaf children who are within the sensitive period for language acquisition. In the meantime, the FDA should require manufacturers to add a highlighted warning to the effect that results with CI vary widely and CIs should not be relied upon to provide adequate auditory input for complete language development in all deaf children. Recent best information on users' experience with CIs (including abandonment) should be clearly provided so that informed decisions can be made. The FDA should require manufacturers' guidance and information materials to include encouragement to parents of deaf children to offer auditory input of a spoken language and visual input of a sign language and to have their child followed closely from birth by developmental specialists in language and cognition. In this way parents can align with providers to prioritize cognitive development and language access in both audio-vocal and visuo-gestural modalities. DISCUSSION: The arguments and recommendations in this paper are discussed at length as they come up.

Prevalence of cochlear implants in Europe: trend between 2010 and 2016.

Objective: To collect figures on the numbers of children and adults receiving cochlear implants across Europe, compare the figures for 2016 with those for 2010, and identify any trends. Materials and methods: In 2018 EURO-CIU invited their 23 member countries to conduct a survey collecting data on the number of CI recipients in 2016 and 2017. Data were received from 15 countries, representing more than 100 000 CI recipients in Europe. Results: For paediatric CI, there was an increase in nearly all European countries (except Denmark, the UK and Luxembourg) between 2010 and 2016. We found an annual figure of one CI per 1000 newborns common in most countries where reimbursement of paediatric CI's is available. Conversely the adult data reveals no increase between 2010 and 2016 and the data is less homogeneous than the paediatric data with huge differences across countries. Conclusion: There is little agreement on data on numbers of CI across Europe, which makes it difficult to plan public health policy, funding or services. In all European countries included in this study (except Germany) there needs to be work on raising more awareness of adult hearing loss and adult cochlear implantation to improve access.

Neural Interface: Frontiers and Applications : Cochlear Implants.

The theory and implementation of modern cochlear implant are presented in this chapter. Major signal processing strategies of cochlear implants are discussed in detail. Hardware implementation including wireless signal transmission circuit, integrated circuit design of implant circuit, and neural response measurement circuit are provided in the latter part of the chapter. Finally, new technologies that are likely to improve the performance of current cochlear implants are introduced.

Neural tracking of the speech envelope in cochlear implant users.

OBJECTIVE: When listening to speech, the brain tracks the speech envelope. It is possible to reconstruct this envelope from EEG recordings. However, in people who hear using a cochlear implant (CI), the artifacts caused by electrical stimulation of the auditory nerve contaminate the EEG. The objective of this study is to develop and validate a method for assessing the neural tracking of speech envelope in CI users. APPROACH: To obtain EEG recordings free of stimulus artifacts, the electrical stimulation is periodically interrupted. During these stimulation gaps, artifact-free EEG can be sampled and used to train a linear envelope decoder. EEG recordings obtained during audible and inaudible (i.e. sub-threshold) stimulation were used to characterize the artifacts and their influence on the envelope reconstruction. MAIN RESULTS: The present study demonstrates for the first time that neural tracking of the speech envelope can be measured in response to ongoing electrical stimulation. The responses were validated to be truly neural and not affected by stimulus artifact. SIGNIFICANCE: Besides applications in audiology and neuroscience, the characterization and elimination of stimulus artifacts will enable future EEG studies involving continuous speech in CI users. Measures of neural tracking of the speech envelope reflect interesting properties of the listener's perception of speech, such as speech intelligibility or attentional state. Successful decoding of neural envelope tracking will open new possibilities to investigate the neural mechanisms of speech perception with a CI.

Trends in sociodemographic disparities of pediatric cochlear implantation over a 15-year period.

OBJECTIVE: Sociodemographic disparities of cochlear implantation in children have been reported. This study sought to determine if disparities in children receiving cochlear implants have narrowed, widened or remained constant. METHODS: Children 18 years or younger who underwent cochlear implantation from 1997 to 2012 were selected using the Kids' Inpatient Database. Demographic data included primary insurance payer, income quartile and race. The Cochran-Armitage test was used to determine if trends were significant. Prevalence rates of cochlear implantation by race were generated. A Poisson regression model was used to evaluate the rates of cochlear implantation within each racial group. RESULTS: The proportion of children receiving cochlear implants with private insurance decreased from 79.3% to 42.6% (p < .0001), whereas children with Medicaid increased from 17.4% to 35.2% (p < .0001). Proportion of implanted children from the lowest two income quartiles increased from 15.5% to 24.4% (p < .0001) and 10.3%-21.8% (p < .0035), respectively. Rates of implantation among children from income quartile four decreased from 50.9% to 35.3% (p < .0001). White children were implanted twice as often as Black or Hispanic children (p = .007 and p = .0012 respectively). Asian children were implanted more than twice as often as Black or Hispanic Children (p = .0154 and p = .0098 respectively). CONCLUSIONS: Income and insurance disparities have narrowed within the inpatient pediatric cochlear implantation cohort. Racial disparities still exist. White and Asian children are implanted at higher rates than Black or Hispanic children.

Cochlear Implant Electrode Array From Partial to Full Insertion in Non-Human Primate Model.

OBJECTIVES: To determine the feasibility of progressive insertion (two sequential surgeries: partial to full insertion) of an electrode array and to compare functional outcomes. MATERIAL AND METHODS: 8 normal-hearing animals (Macaca fascicularis (MF)) were included. A 14 contact electrode array, which is suitably sized for the MF cochlea was partially inserted (PI) in 16 ears. After 3 months of follow-up revision surgery the electrode was advanced to a full insertion (FI) in 8 ears. Radiological examination and auditory testing was performed monthly for 6 months. In order to compare the values a two way repeated measures ANOVA was used. A p-value below 0.05 was considered as statistically significant. IBM SPSS Statistics V20 was used. RESULTS: Surgical procedure was completed in all cases with no complications. Mean auditory threshold shift (ABR click tones) after 6 months follow-up is 19 dB and 27 dB for PI and FI group. For frequencies 4, 6, 8, 12, and 16 kHz in the FI group, tone burst auditory thresholds increased after the revision surgery showing no recovery thereafter. Mean threshold shift at 6 months of follow- up is 19.8 dB ranging from 2 to 36dB for PI group and 33.14dB ranging from 8 to 48dB for FI group. Statistical analysis yields no significant differences between groups. CONCLUSION: It is feasible to perform a partial insertion of an electrode array and progress on a second surgical time to a full insertion (up to 270º). Hearing preservation is feasible for both procedures. Note that a minimal threshold deterioration is depicted among full insertion group, especially among high frequencies, with no statistical differences.

Should patients with brain implants undergo MRI?

Patients suffering from neuronal degenerative diseases are increasingly being equipped with neural implants to treat symptoms or restore functions and increase their quality of life. Magnetic resonance imaging (MRI) would be the modality of choice for the diagnosis and compulsory postoperative monitoring of such patients. However, interactions between the magnetic resonance (MR) environment and implants pose severe health risks to the patient. Nevertheless, neural implant recipients regularly undergo MRI examinations, and adverse events are rarely reported. However, this should not imply that the procedures are safe. More than 300 000 cochlear implant recipients are excluded from MRI, unless the indication outweighs the excruciating pain. For 75 000 deep brain stimulation (DBS) recipients quite the opposite holds true: MRI is considered an essential part of the implantation procedure and some medical centres deliberately exceed safety regulations, which they refer to as crucially impractical. Permanent MRI-related neurological dysfunctions in DBS recipients have occurred in the past when manufacturer recommendations were exceeded. Within the last few decades, extensive effort has been invested to identify, characterise and quantify the occurring interactions. Yet today we are still far from a satisfying solution concerning a safe and beneficial MR procedure for all implant recipients. To contribute, we intend to raise awareness of the growing concern, summon the community to stop absurdities and instead improve the situation for the increasing number of patients. Therefore, we review implant safety in the MRI literature from an engineering point of view, with a focus on cochlear and DBS implants as success stories of neural implants in clinical practice. We briefly explain fundamental phenomena which can lead to patient harm, and point out breakthroughs and errors made. Then, we end with conclusions and strategies to avoid future implants from being contraindicated in MR examinations. We believe that implant recipients should enter MRI, but before doing so, it should be made sure that the procedure is reasonable.

Considerations and Rationale for Cochlear Implant Electrode Design - Past, Present and Future.

The electrode array of a cochlear implant forms a permanent, often lifelong interface between the implanted electronics and neural structures of the cochlea. A cochlear implant is primarily prescribed to restore hearing via electrical stimulation of the auditory nerve. As with any neural stimulator intended to either deliver electrical stimulus or record a neural response, the aim is to place the electrodes in close proximity to the target neural structures. The broadening of indications and the concept of preservation of low-frequency residual hearing over the last two decades has resulted in an increased understanding of the mechanisms and implications of intracochlear trauma for both the hearing preservation surgery and electrical stimulation outcomes with cochlear implantation, as well as the influence of many biographic and audiological patient factors correlated with achieving better hearing outcomes. These two goals, the proximity to the cochlear nerve for electrical stimulation and the preservation of cochlear structures, have typically been viewed as mutually exclusive, with perimodiolar electrode arrays being preferred for the former, and lateral wall electrode arrays for the latter. The design evolution of both the lateral wall and perimodiolar electrodes is presented, considering the cochlea anatomy and continued understanding of the mechanics and dynamics of electrode insertion, along with the influence of the ongoing changes to the intracochlear environment to provide a rationale for the electrode design with the intent to provide the greatest patient benefit over their implanted lifetime.

Towards a Complete In Silico Assessment of the Outcome of Cochlear Implantation Surgery.

Cochlear implantation (CI) surgery is a very successful technique, performed on more than 300,000 people worldwide. However, since the challenge resides in obtaining an accurate surgical planning, computational models are considered to provide such accurate tools. They allow us to plan and simulate beforehand surgical procedures in order to maximally optimize surgery outcomes, and consequently provide valuable information to guide pre-operative decisions. The aim of this work is to develop and validate computational tools to completely assess the patient-specific functional outcome of the CI surgery. A complete automatic framework was developed to create and assess computationally CI models, focusing on the neural response of the auditory nerve fibers (ANF) induced by the electrical stimulation of the implant. The framework was applied to evaluate the effects of ANF degeneration and electrode intra-cochlear position on nerve activation. Results indicate that the intra-cochlear positioning of the electrode has a strong effect on the global performance of the CI. Lateral insertion provides better neural responses in case of peripheral process degeneration, and it is recommended, together with optimized intensity levels, in order to preserve the internal structures. Overall, the developed automatic framework provides an insight into the global performance of the implant in a patient-specific way. This enables to further optimize the functional performance and helps to select the best CI configuration and treatment strategy for a given patient.

Cochlear Implants Meet Regenerative Biology: State of the Science and Future Research Directions.

: The cochlear implant, the first device to restore a human sense, is an electronic substitute for lost mechanosensory hair cells. It has been successful at providing hearing to people with severe to profound hearing loss and as of 2012, an estimated 324,000 patients worldwide have received cochlear implants. Users of cochlear implants however, suffer from difficulties in processing complex sounds such as music and in discriminating sounds in noisy environments. Recent advances in regenerative biology and medicine are opening new avenues for enhancing the efficacy of cochlear implants by improving the neural interface in the future and offer the possibility of an entirely biological solution for hearing loss in the long term. This report comprises the latest developments presented in the first Symposium on cochlear implants and regenerative biology, held at the 14th International Conference on Cochlear Implants in 2016 in Toronto, Canada.

NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons.

: Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through 1) low frequency resolution, hence sub-optimal sound quality and 2), large stimulation currents, hence high energy consumption (responsible for significant battery costs and for impeding the development of fully implantable systems). A recently completed, multinational and interdisciplinary project called NANOCI aimed at overcoming current limitations by creating a gapless interface between auditory nerve fibers and the cochlear implant electrode array. This ambitious goal was achieved in vivo by neurotrophin-induced attraction of neurites through an intracochlear gel-nanomatrix onto a modified nanoCI electrode array located in the scala tympani of deafened guinea pigs. Functionally, the gapless interface led to lower stimulation thresholds and a larger dynamic range in vivo, and to reduced stimulation energy requirement (up to fivefold) in an in vitro model using auditory neurons cultured on multi-electrode arrays. In conclusion, the NANOCI project yielded proof of concept that a gapless interface between auditory neurons and cochlear implant electrode arrays is feasible. These findings may be of relevance for the development of future CI systems with better sound quality and performance and lower energy consumption. The present overview/review paper summarizes the NANOCI project history and highlights achievements of the individual work packages.

Challenges in Improving Cochlear Implant Performance and Accessibility.

Here I identify two gaps in cochlear implants that have been limiting their performance and acceptance. First, cochlear implant performance has remained largely unchanged, despite the number of publications tripling per decade in the last 30 years. Little has been done so far to address a fundamental limitation in the electrode-to-neuron interface, with the electrode size being a thousand times larger than the neuron diameter while the number of electrodes being a thousand times less. Both the small number and the large size of electrodes produce broad spatial activation and poor frequency resolution that limit current cochlear implant performance. Second, a similarly rapid growth in cochlear implant volume has not produced an expected decrease in unit price in the same period. The high cost contributes to low market penetration rate, which is about 20% in developed countries and less than 1% in developing countries. I will discuss changes needed in both research strategy and business practice to close the gap between prosthetic and normal hearing as well as that between haves and have-nots.