Cochlear Implant Research

The Effects of Intracochlear Electrical Stimulation on Neural Survival and Function

It is not an exaggeration to say that the cochlear implant (CI) has revolutionized the rehabilitation of individuals with severe to profound sensorineural hearing loss. Almost all adult CI recipients enjoy significantly enhanced lip-reading capabilities, and a majority of those using the latest technology score above 80-percent correct on high-context sentences without visual cues. Further, CI electrodes are now being implanted and used in combination with hearing aids in individuals with significant residual hearing. The success of this electrical-acoustical (EAS) hearing has re-focused attention on reducing trauma during CI implantation, maintaining residual hearing, and on the importance of the condition of the cochlea and auditory nerve in CI function. In fact, exogenous delivery of the neurotrophin BDNF has been proposed for human CI subjects to promote improved auditory nerve survival, and CI electrodes modified for drug delivery have already been developed. However, animal studies examining the effects of intracochlear delivery of BDNF in promoting auditory nerve survival are extremely limited to date, and we believe several critical issues must be addressed prior to considering human application.

Further, thousands of very young deaf children, including congenitally deaf infants, now are receiving CIs. It is encouraging that many of these children eventually are mainstreamed into public education settings. However, other pediatric CI recipients lag far behind in language development and some children cannot even discriminate between the most basal and most apical electrodes of their implants. Thus, beyond the bioengineering challenges in maintaining a CI over the lifetime of an implanted child, there are important developmental and neurobiological issues concerning the effects of ICES on the immature auditory system. The rationale for implanting at very young ages is based on the belief that there is a critical period for language acquisition as suggested by the profound effects of auditory deprivation in congenitally deaf children and adults and by research demonstrating that implantation before the age of 2 results in significant advantages in speech perception.

Many animal studies have suggested that auditory deprivation during maturation is especially harmful in causing degeneration/reorganization in the central auditory system. With pediatric CIs, it is generally assumed that restoring input during this critical period will be more effective in preventing the degenerative consequences of deafness and that the immature auditory system will be more plastic, better able to adapt to ICES. But it is important to recognize that the increased plasticity that characterizes critical periods of nervous system development might also have negative consequences. ICES delivered in a particular format might entrain the immature auditory system into an idiosyncratic organization that could be suboptimal for effective processing of other patterns or formats of ICES introduced later in life. Studies in the visual system show that early restricted or aberrant inputs can have profound effects on central nervous system development that are irreversible due to developmental critical periods. Broadly distributed, synchronous input to the retina (e.g., electrical stimulation of the optic nerve or stroboscopic illumination) in the immature visual system causes profound changes in central processing that are not reversible if normal visual input is later restored.

The overall premise in our ICES research is that with so many very young (<12 months) congenitally deaf children now receiving CIs, it is critical to better understand the effects of ICES on the developing auditory system. Our previous work focused on defining the effects of total auditory deprivation and highly controlled, unilateral ICES in neonatally deafened animals. Significant progress has been made, but many important questions remain.

Previous studies conducted by our research group at UCSF have shown that chronic intracochlear electrical stimulation (ICES) delivered by a cochlear implant (CI) can promote significantly improved survival of auditory nerve neurons. However, ICES can also induce potentially negative functional changes in the central auditory system in an model of pediatric deafness. The overall objective of this proposed research is to explore the mechanisms by which ICES and/or neurotrophic agents can optimize anatomical and functional integrity of the deafened auditory system. Our long-term goal is to develop methods and protocols that can be applied in human CI recipients to help optimize the function of a multichannel auditory prosthesis.

The specific aims of this research are:

• To explore the mechanisms by which chronic ICES promotes the survival of auditory nerve neurons in profound hearing loss that has occurred early in life. In particular, to examine possible interactive effects of co-administration of ICES and neurotrophic or anti-inflammatory agents. We would also like to determine whether there is a developmental critical period for the survival-promoting effects of these neurotrophic agents.

• To study the influence of early deafness with ICES on degradation in the selectivity of auditory nerve projections to the cochlear nucleus, specifically, whether such changes underlie and parallel the functional alterations seen in the central auditory system after chronic ICES.

• To examine the structural and functional changes within the central auditory system elicited by deafness and various formats of chronic ICES, and to determine whether functional alterations recorded after prolonged periods of deafness are primarily related to degeneration of the auditory nerve in the cochlea or to degenerative alterations in the central auditory system.

• To determine whether potentially negative functional changes in the central auditory system induced by chronic ICES delivered on a single broadband CI channel are reversible later in life after introducing competitive inputs delivered on 2 or more intracochlear ICES channels of asynchronous patterned stimulation.

Estimating Optimum Insertion Depth for the HiFocus Electrode Array in Individual Human Cochleae Based on High-Resolution Computed-Tomography (CT) Images

Despite the wide use of contemporary cochlear implants (CI) with significantly improved designs and advanced speech-coding strategies, the performance outcome of CI users remains extremely variable -- even among individuals with a similar deafness history, the same implanted electrode arrays and speech processor strategies. Normal anatomical variability among individual cochleae is often overlooked as a factor potentially contributing to the wide range of performance with the CI and is not taken into account in routine cochlear implant surgery or speech processor fitting. Lack of thorough information on the intracochlear position of individual electrodes as well as a high rate of insertion trauma associated with deeper insertions raises the question of whether more precise control over insertion depth can improve outcomes with the CI. Our previous studies demonstrated a significant correlation between the organ of Corti (OC) and the spiral ganglion (SG) lengths (two structures defining frequency tuning in the cochlea) and the diameter of the cochlea's basal turn – a metric that can be obtained from CT images in living subjects. This study will extend the previous work by determining the reliability of CT measurements of individual cochlear dimensions for optimization of cochlear implant insertion depth and prevention of trauma.

Optimization of the insertion depth of the electrode array can significantly reduce the extent of trauma caused during the implantation. We hypothesize that analysis of the anatomical dimensions of the cochlea obtained on CT images prior to implant surgery can provide more detailed information about the insertion depth required to cover the optimum frequency range without increasing the risk of over-insertion and thereby improve the frequency resolution for individual channels resulting in better speech performance of CI users. Estimation of the optimum insertion depth is also important for preservation of residual hearing in candidates for combined acoustic and electrical stimulation.

The overall goal of this project is to improve the reliability of optimum positioning and atraumatic insertion of CI electrodes based on the characteristics of individual cochleae that can be obtained from pre-surgery CT scans. Suboptimal placement of the electrode array is associated with a higher rate of insertion trauma, a reduction in pitch perception ability, and loss of residual hearing in patients with combined acoustic and electrical stimulation. This study will determine whether the size of the individual cochlea estimated on high resolution CT images can define the optimum insertion depth, help to guide electrode insertion to the desired frequency range, and also prevent trauma.

Development of New Field-Shaping Stimulation Strategies

As the overall population ages, the number of cochlear implant (CI) users (currently greater than 100,000) is projected to increase substantially, especially as the criteria for CI candidacy are relaxed to include people with unilateral impairment and people with only high-frequency hearing loss (candidates for so-called electrical-acoustical stimulation, or EAS). Whereas current CIs employ arrays of 12 to 22 physical electrodes, psychophysical studies indicate that user performance using current CIs is equivalent to a significantly smaller number of information channels, usually 4 to 8. That is, most of the physical electrodes in contemporary CIs either are ineffective, or are ineffectively used, as channels for information. The importance of providing a large number of spectral information channels to CI users has been demonstrated by psychophysical studies modeling CI sound processing with normal-hearing listeners; these studies show that speech reception, especially in noise, and music perception are degraded as the number of spectral information channels is progressively limited. Thus, gains in CI user performance would be realized if the number of effective channels could be increased.

The number of effective CI channels is limited by the current spread in the cochlea. Current spread can be controlled by using stimulation paradigms that shape the electric field within the cochlea (e.g., current steering and current focusing). By controlling the location and spread of the electric field, such paradigms are able to target selective tonotopic regions of the surviving auditory nerve beyond, and more precisely than, those that are targeted via conventional stimulation using activation of individual physical electrodes or bipolar electrode pairs. Thus, these field-shaping stimulation paradigms have the potential to increase the number of effective information channels beyond those provided by conventional stimulation paradigms. While some field-shaping stimulation protocols are now beginning to be applied clinically, the factors influencing efficacy of these protocols have not been completely evaluated. Thus, it is unlikely that the protocols used today are optimal. Additional field-shaping protocols (e.g., phantom electrode stimulation, or PES), and combining field-shaping with pulse-shaping (e.g. pseudomonophasic pulses), are likely to further enhance efficacy above current implementations. In particular, the ability to selectively activate sectors of the auditory nerve lying beyond the range of the physical electrodes using PES is of special relevance for CI users with shortened EAS electrodes, and for other users would provide access to cochlear regions corresponding to speech fundamental frequencies.

Our ultimate goal is to increase the number of effective information channels for current CI users, as well as future CI users. Our central hypothesis, based upon findings from our own work and from other investigators, is that application of field-shaping stimulation strategies (along with informed alterations in cochlear implant device design) can substantially increase the number of information channels available to CI users.

The specific aims of this research are:

• To evaluate the efficacy of field-shaping strategies (current steering, current focusing, and phantom electrode) in creating selective and discriminable “virtual” CI channels that augment the channels corresponding to physical CI electrodes.

• To evaluate the dependence of field-shaping efficacy upon specific factors that are hypothesized to limit this efficacy, including CI electrode radial position and longitudinal separation within the scala tympani (ST), ST longitudinal conductivity, and auditory nerve survival.

Successful completion of these studies and subsequent translation to clinical implementations will increase the number of information channels available to current and future CI users, and therefore enhance auditory perception for this expanding population.