A Broadly Applicable Method for Characterizing the Slope of the Electrically Evoked Compound Action Potential Amplitude Growth Function.

OBJECTIVES: Amplitudes of electrically evoked compound action potentials (eCAPs) as a function of the stimulation level constitute the eCAP amplitude growth function (AGF). The slope of the eCAP AGF (i.e., rate of growth of eCAP amplitude as a function of stimulation level), recorded from subjects with cochlear implants (CIs), has been widely used as an indicator of survival of cochlear nerve fibers. However, substantial variation in the approach used to calculate the slope of the eCAP AGF makes it difficult to compare results across studies. In this study, we developed an improved slope-fitting method by addressing the limitations of previously used approaches and ensuring its application for the estimation of the maximum slopes of the eCAP AGFs recorded in both animal models and human listeners with various etiologies. DESIGN: The new eCAP AGF fitting method was designed based on sliding window linear regression. Slopes of the eCAP AGF estimated using this new fitting method were calculated and compared with those estimated using four other fitting methods reported in the literature. These four methods were nonlinear regression with a sigmoid function, linear regression, gradient calculation, and boxcar smoothing. The comparison was based on the fitting results of 72 eCAP AGFs recorded from 18 acutely implanted guinea pigs, 46 eCAP AGFs recorded from 23 chronically implanted guinea pigs, and 2094 eCAP AGFs recorded from 200 human CI users from 4 patient populations. The effect of the choice of input units of the eCAP AGF (linear versus logarithmic) on fitting results was also evaluated. RESULTS: The slope of the eCAP AGF was significantly influenced by the slope-fitting method and by the choice of input units. Overall, slopes estimated using all five fitting methods reflected known patterns of neural survival in human patient populations and were significantly correlated with speech perception scores. However, slopes estimated using the newly developed method showed the highest correlation with spiral ganglion neuron density among all five fitting methods for animal models. In addition, this new method could reliably and accurately estimate the slope for 4 human patient populations, while the performance of the other methods was highly influenced by the morphology of the eCAP AGF. CONCLUSIONS: The novel slope-fitting method presented in this study addressed the limitations of the other methods reported in the literature and successfully characterized the slope of the eCAP AGF for various animal models and CI patient populations. This method may be useful for researchers in conducting scientific studies and for clinicians in providing clinical care for CI users.

How electrically evoked compound action potentials in chronically implanted guinea pigs relate to auditory nerve health and electrode impedance.

This study examined how multiple measures based on the electrically evoked compound action potential (ECAP) amplitude-growth functions (AGFs) were related to estimates of neural [spiral ganglion neuron (SGN) density and cell size] and electrode impedance measures in 34 specific pathogen free pigmented guinea pigs that were chronically implanted (4.9-15.4 months) with a cochlear implant electrode array. Two interphase gaps (IPGs) were used for the biphasic pulses and the effect of the IPG on each ECAP measure was measured ("IPG effect"). When using a stimulus with a constant IPG, SGN density was related to the across-subject variance in ECAP AGF linear slope, peak amplitude, and N1 latency. The SGN density values also help to explain a significant proportion of variance in the IPG effect for AGF linear slope and peak amplitude measures. Regression modeling revealed that SGN density was the primary dependent variable contributing to across-subject variance for ECAP measures; SGN cell size did not significantly improve the fitting of the model. Results showed that simple impedance measures were weakly related to most ECAP measures but did not typically improve the fit of the regression model.

Assessing the Relationship Between the Electrically Evoked Compound Action Potential and Speech Recognition Abilities in Bilateral Cochlear Implant Recipients.

OBJECTIVES: The primary objective of the present study was to examine the relationship between suprathreshold electrically evoked compound action potential (ECAP) measures and speech recognition abilities in bilateral cochlear implant listeners. We tested the hypothesis that the magnitude of ear differences in ECAP measures within a subject (right-left) could predict the difference in speech recognition performance abilities between that subject's ears (right-left). DESIGN: To better control for across-subject variables that contribute to speech understanding, the present study used a within-subject design. Subjects were 10 bilaterally implanted adult cochlear implant recipients. We measured ECAP amplitudes and slopes of the amplitude growth function in both ears for each subject. We examined how each of these measures changed when increasing the interphase gap of the biphasic pulses. Previous animal studies have shown correlations between these ECAP measures and auditory nerve survival. Speech recognition measures included speech reception thresholds for sentences in background noise, as well as phoneme discrimination in quiet and in noise. RESULTS: Results showed that the between-ear difference (right-left) of one specific ECAP measure (increase in amplitude growth function slope as the interphase gap increased from 7 to 30 µs) was significantly related to the between-ear difference (right-left) in speech recognition. Frequency-specific response patterns for ECAP data and consonant transmission cues support the hypothesis that this particular ECAP measure may represent localized functional acuity. CONCLUSIONS: The results add to a growing body of literature suggesting that when using a well-controlled research design, there is evidence that underlying neural function is related to postoperative performance with a cochlear implant.

Evaluating multipulse integration as a neural-health correlate in human cochlear-implant users: Relationship to forward-masking recovery.

The present study evaluated the slopes of threshold-versus-pulse-rate functions (multipulse integration, MPI) in humans with cochlear implants in relation to recovery from 300-ms forward maskers. MPI has been correlated with spiral ganglion cell density in animals. The present study showed that steeper MPI functions were correlated with faster recovery from forward masking. The findings suggested that the variations in the MPI slopes are explained not only by the quantity of neurons contributing to the integration process but also by the neurons' temporal response characteristics and possibly central inhibition.

Evaluating multipulse integration as a neural-health correlate in human cochlear-implant users: Relationship to spatial selectivity.

The decrease of psychophysical detection thresholds as a function of pulse rate for a fixed-duration electrical pulse train is referred to as multipulse integration (MPI). The MPI slopes correlate with anatomical and physiological indices of cochlear health in guinea pigs with cochlear implants. The aim of the current study was to assess whether the MPI slopes were related to the spatial spread of activation by electrical stimulation. The hypothesis was that MPI is dependent on the total number of excitable neurons at the stimulation site, with broader neural excitation producing a steeper threshold decrease as a function of stimulation rate. MPI functions were measured at all stimulation sites in 22-site electrode arrays in human subjects. Some sites with steep MPI functions and other sites with shallow functions were assessed for spatial spread of excitation at 900 pps using a forward-masking paradigm. The results showed a correlation between the slopes of the forward-masking functions and the steepness of MPI, with broader stimulation predicting greater integration. The results are consistent with the idea that integration of multiple pulses in a pulse train relies on the number of excitable neurons at the stimulation site.

Effects of site-specific level adjustments on speech recognition with cochlear implants.

OBJECTIVES: Modulation detection thresholds (MDTs) vary across stimulation sites in a cochlear implant (CI) electrode array in a manner that is subject and ear specific. Previous studies have demonstrated that speech recognition with a CI can be improved by site-selection strategies, where selected stimulation sites with poor modulation sensitivity are removed from a subject's processor MAP. Limitations of site-selection strategies are that they can compromise spectral resolution and distort frequency-place mapping because the frequencies assigned to the removed sites are usually reallocated to other sites, and site bandwidths are broadened. The objective of the present study was to test an alternative approach for rehabilitation that aimed at improving the across-site mean MDTs by adjusting stimulation parameters at the poorly performing sites. On the basis of previous findings that modulation detection contributes to speech recognition and improves significantly with stimulus level, the authors hypothesized that modulation sensitivity at the poor sites could be improved by artificially increasing stimulation levels at those sites in the speech processor, which then would lead to improved speech recognition. DESIGN: Nine postlingually deafened ears implanted with Nucleus CIs were evaluated for MDTs, absolute-detection threshold levels (T levels), and the maximum loudness levels (C levels) on each of the available stimulation sites. For each ear, the minimum stimulation level settings in the speech-processor MAP were raised by 5%, and alternatively by 10%, of the dynamic range (DR) from true thresholds on five stimulation sites with the poorest MDTs. For comparison, a 5% level raise was applied globally to all stimulation sites. The C levels were fixed during these level manipulations. MDTs at the five poorest stimulation sites were compared at 20% DR before and after the level adjustments. Speech-reception thresholds (SRTs), that is, signal to noise ratios required for 50% correct speech recognition, were evaluated for these MAPs using CUNY sentences. The site-specific level-adjusted MAPs were compared with the global-level-adjusted MAP and the MAP without level adjustment. The effects on speech recognition of adjusting the minimal stimulation level settings on the five poorest stimulation sites were also compared with effects of removing these sites from the speech-processor MAP. RESULTS: The 5% level increase on the five electrodes with the worst MDTs resulted in an improvement in the group mean SRT of 2.36 dB SNR relative to the MAP without level adjustment. The magnitude of level increase that resulted in the greatest SRT improvement for individuals varied across ears. MDTs measured at 20% DR significantly improved on the poor sites after the level adjustment that resulted in the best SRT for that ear was applied. Increasing the minimal stimulation levels on all stimulation sites or removing sites selected for rehabilitation, the parsimonious approaches, did not improve SRTs. CONCLUSIONS: The site-specific adjustments of the T level settings improved modulation sensitivity at low levels and significantly improved subjects' SRTs. Thus, this site-rehabilitation strategy was an effective alternative to site-selection strategies for improving speech recognition in CI users.

Relationship between multipulse integration and speech recognition with cochlear implants.

Comparisons of performance with cochlear implants and postmortem conditions in the cochlea in humans have shown mixed results. The limitations in those studies favor the use of within-subject designs and non-invasive measures to estimate cochlear conditions. One non-invasive correlate of cochlear health is multipulse integration, established in an animal model. The present study used this measure to relate neural health in human cochlear implant users to their speech recognition performance. The multipulse-integration slopes were derived based on psychophysical detection thresholds measured for two pulse rates (80 and 640 pulses per second). A within-subject design was used in eight subjects with bilateral implants where the direction and magnitude of ear differences in the multipulse-integration slopes were compared with those of the speech-recognition results. The speech measures included speech reception threshold for sentences and phoneme recognition in noise. The magnitude of ear difference in the integration slopes was significantly correlated with the magnitude of ear difference in speech reception thresholds, consonant recognition in noise, and transmission of place of articulation of consonants. These results suggest that multipulse integration predicts speech recognition in noise and perception of features that use dynamic spectral cues.

Using temporal modulation sensitivity to select stimulation sites for processor MAPs in cochlear implant listeners.

Previous studies in our laboratory showed that temporal acuity as assessed by modulation detection thresholds (MDTs) varied across activation sites and that this site-to-site variability was subject specific. Using two 10-channel MAPs, the previous experiments showed that processor MAPs that had better across-site mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs tested in the same subject. The current study extends our earlier work on developing more optimal-fitting strategies to test the feasibility of using a site-selection approach in the clinical domain. This study examined the hypothesis that revising the clinical speech processor MAP for cochlear implant (CI) recipients by turning off selected sites that have poorer temporal acuity and reallocating frequencies to the remaining electrodes would lead to improved speech recognition. Twelve CI recipients participated in the experiments. We found that site selection procedure based on MDTs in the presence of a masker resulted in improved performance on consonant recognition and recognition of sentences in noise. In contrast, vowel recognition was poorer with the experimental MAP than with the clinical MAP, possibly due to reduced spectral resolution when sites were removed from the experimental MAP. Overall, these results suggest a promising path for improving recipient outcomes using personalized processor-fitting strategies based on a psychophysical measure of temporal acuity.

Association of Aging and Cognition With Complex Speech Understanding in Cochlear-Implanted Adults: Use of a Modified National Institutes of Health (NIH) Toolbox Cognitive Assessment.

Importance: The association between cognitive function and outcomes in cochlear implant (CI) users is not completely understood, partly because some cognitive tests are confounded by auditory status. It is important to determine appropriate cognitive tests to use in a cohort of CI recipients. Objective: To provide proof-of-concept for using an adapted version of the National Institutes of Health (NIH) Toolbox Cognition Battery in a cohort of patients with CIs and to explore how hearing in noise with a CI is affected by cognitive status using the adapted test. Design, Setting, and Participants: In this prognostic study, participants listened to sentences presented in a speech-shaped background noise. Cognitive tests consisted of 7 subtests of the NIH Toolbox Cognition Battery that were adapted for hearing impaired individuals by including written instructions and visual stimuli. Participants were prospectively recruited from and evaluated at a tertiary medical center. All participants had at least 6 months' experience with their CI. Main Outcomes and Measures: The main outcomes were performance on the adapted cognitive test and a speech recognition in noise task. Results: Participants were 20 adult perilingually or postlingually deafened CI users (50% male participants; median [range] age, 66 [26-80] years old). Performance on a sentence recognition in noise task was negatively associated with the chronological age of the listener (R2 = 0.29; ß = 0.16; standard error, SE = 0.06; t = 2.63; 95% confidence interval, 0.03-0.27). Testing using the adapted version of the NIH Toolbox Cognition Battery revealed that a test of processing speed was also associated with performance, using a standardized score that accounted for contributions of other demographic factors (R2 = 0.28; 95% confidence interval, -0.42 to -0.05). Conclusions and Relevance: In this prognostic study, older CI users showed poorer performance on a sentence-in-noise test compared with younger users. This poorer performance was correlated with a cognitive deficit in processing speed when cognitive function was assessed using a test battery adapted for participants with hearing loss. These results provide initial proof-of-concept results for using a standardized and adapted cognitive test battery in CI recipients.

Reexamining the effects of electrode location on measures of neural health in cochlear implant users.

The electrically evoked compound action potentials (ECAPs) amplitude-growth function (AGF) slope correlates with spiral ganglion neuron (SGN) density in the cochlear implanted cochlea. Electrode insertion angle and medial-lateral distance covary from base to apex; in some human ears, SGN survival varies from base to apex, making it difficult to parse out contributing factors to the ECAP AGF slope. Evoked compound action potentials were analyzed on each electrode and compared to post-operative computerized tomography scans. When controlling for medial-lateral distance, insertion angle does not influence ECAP AGF slope.

Cochlear Health and Cochlear-implant Function.

The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs are able to effectively improve hearing in nearly all recipients and can substantially improve speech understanding and quality of life for patients with significant hearing loss. A wealth of research has focused on underlying factors that contribute to success with a CI, and recent evidence suggests that the overall health of the cochlea could potentially play a larger role than previously recognized. This article defines and reviews attributes of cochlear health and describes procedures to evaluate cochlear health in humans and animal models in order to examine the effects of cochlear health on performance with a CI. Lastly, we describe how future biologic approaches can be used to preserve and/or enhance cochlear health in order to maximize performance for individual CI recipients.

Psychophysically based site selection coupled with dichotic stimulation improves speech recognition in noise with bilateral cochlear implants.

The ability to perceive important features of electrical stimulation varies across stimulation sites within a multichannel implant. The aim of this study was to optimize speech processor MAPs for bilateral implant users by identifying and removing sites with poor psychophysical performance. The psychophysical assessment involved amplitude-modulation detection with and without a masker, and a channel interaction measure quantified as the elevation in modulation detection thresholds in the presence of the masker. Three experimental MAPs were created on an individual-subject basis using data from one of the three psychophysical measures. These experimental MAPs improved the mean psychophysical acuity across the electrode array and provided additional advantages such as increasing spatial separations between electrodes and/or preserving frequency resolution. All 8 subjects showed improved speech recognition in noise with one or more experimental MAPs over their everyday-use clinical MAP. For most subjects, phoneme and sentence recognition in noise were significantly improved by a dichotic experimental MAP that provided better mean psychophysical acuity, a balanced distribution of selected stimulation sites, and preserved frequency resolution. The site-selection strategies serve as useful tools for evaluating the importance of psychophysical acuities needed for good speech recognition in implant users.

Across-site patterns of modulation detection: relation to speech recognition.

The aim of this study was to identify across-site patterns of modulation detection thresholds (MDTs) in subjects with cochlear implants and to determine if removal of sites with the poorest MDTs from speech processor programs would result in improved speech recognition. Five hundred millisecond trains of symmetric-biphasic pulses were modulated sinusoidally at 10 Hz and presented at a rate of 900 pps using monopolar stimulation. Subjects were asked to discriminate a modulated pulse train from an unmodulated pulse train for all electrodes in quiet and in the presence of an interleaved unmodulated masker presented on the adjacent site. Across-site patterns of masked MDTs were then used to construct two 10-channel MAPs such that one MAP consisted of sites with the best masked MDTs and the other MAP consisted of sites with the worst masked MDTs. Subjects' speech recognition skills were compared when they used these two different MAPs. Results showed that MDTs were variable across sites and were elevated in the presence of a masker by various amounts across sites. Better speech recognition was observed when the processor MAP consisted of sites with best masked MDTs, suggesting that temporal modulation sensitivity has important contributions to speech recognition with a cochlear implant.

Estimating health of the implanted cochlea using psychophysical strength-duration functions and electrode configuration.

It is generally believed that the efficacy of cochlear implants is partly dependent on the condition of the stimulated neural population. Cochlear pathology is likely to affect the manner in which neurons respond to electrical stimulation, potentially resulting in differences in perception of electrical stimuli across cochlear implant recipients and across the electrode array in individual cochlear implant users. Several psychophysical and electrophysiological measures have been shown to predict cochlear health in animals and were used to assess conditions near individual stimulation sites in humans. In this study, we examined the relationship between psychophysical strength-duration functions and spiral ganglion neuron density in two groups of guinea pigs with cochlear implants who had minimally-overlapping cochlear health profiles. One group was implanted in a hearing ear (N = 10) and the other group was deafened by cochlear perfusion of neomycin, inoculated with an adeno-associated viral vector with an Ntf3-gene insert (AAV.Ntf3) and implanted (N = 14). Psychophysically measured strength-duration functions for both monopolar and tripolar electrode configurations were then compared for the two treatment groups. Results were also compared to their histological outcomes. Overall, there were considerable differences between the two treatment groups in terms of their psychophysical performance as well as the relation between their functional performance and histological data. Animals in the neomycin-deafened, neurotrophin-treated, and implanted group (NNI) exhibited steeper strength-duration function slopes; slopes were positively correlated with SGN density (steeper slopes in animals that had higher SGN densities). In comparison, the implanted hearing (IH) group had shallower slopes and there was no relation between slopes and spiral ganglion density. Across all animals, slopes were negatively correlated with ensemble spontaneous activity levels (shallower slopes with higher ensemble spontaneous activity levels). We hypothesize that differences in strength-duration function slopes between the two treatment groups were related to the condition of the inner hair cells, which generate spontaneous activity that could affect the across-fiber synchrony and/or the size of the population of neural elements responding to electrical stimulation. In addition, it is likely that spiral ganglion neuron peripheral processes were present in the IH group, which could affect membrane properties of the stimulated neurons. Results suggest that the two treatment groups exhibited distinct patterns of variation in conditions near the stimulating electrodes that altered detection thresholds. Overall, the results of this study suggest a complex relationship between psychophysical detection thresholds for cochlear implant stimulation and nerve survival in the implanted cochlea. This relationship seems to depend on the characteristics of the electrical stimulus, the electrode configuration, and other biological features of the implanted cochlea such as the condition of the inner hair cells and the peripheral processes.

Components of impedance in a cochlear implant animal model with TGFß1-accelerated fibrosis.

Outcomes of cochlear implantation are likely influenced by the biological state of the cochlea. Fibrosis is a pathological change frequently seen in implanted ears. The goal of this work was to investigate the relationship between fibrosis and impedance. To that end, we employed an animal model of extensive fibrosis and tested whether aspects of impedance differed from controls. Specifically, an adenovirus with a TGF-ß1 gene insert (Ad.TGF-ß1) was injected into guinea pig scala tympani to elicit rapid onset fibrosis and investigate the relation between fibrosis and impedance. We found a significant correlation between treatment and rate of impedance increase. A physical circuit model of impedance was used to separate the effect of fibrosis from other confounding factors. Supported by preliminary, yet nonconclusive, electron microscopy data, this modeling suggested that deposits on the electrode surface are an important contributor to impedance change over time.

Effects of electrode configuration on cochlear implant modulation detection thresholds.

Cochlear implant function, as assessed by psychophysical measures, varies from one stimulation site to another within a patient's cochlea. This suggests that patient performance might be improved by selection of the best-functioning sites for the processor map. In evaluating stimulation sites for such a strategy, electrode configuration is an important variable. Variation across stimulation sites in loudness-related measures (detection thresholds and maximum comfortable loudness levels), is much larger for stimulation with bipolar electrode configurations than with monopolar configurations. The current study found that, in contrast to the loudness-related measures, magnitudes of across-site means and the across-site variances of modulation detection thresholds were not dependent on electrode configuration, suggesting that the mechanisms underlying variation in these various psychophysical measures are not all the same. The data presented here suggest that bipolar and monopolar electrode configurations are equally effective in identifying good and poor stimulation sites for modulation detection but that the across-site patterns of modulation detection thresholds are not the same for the two configurations. Therefore, it is recommended to test all stimulation sites using the patient's clinically assigned electrode configuration when performing psychophysical evaluation of a patient's modulation detection acuity to select sites for the processor map.

Detection of pulse trains in the electrically stimulated cochlea: effects of cochlear health.

Perception of electrical stimuli varies widely across users of cochlear implants and across stimulation sites in individual users. It is commonly assumed that the ability of subjects to detect and discriminate electrical signals is dependent, in part, on conditions in the implanted cochlea, but evidence supporting that hypothesis is sparse. The objective of this study was to define specific relationships between the survival of tissues near the implanted electrodes and the functional responses to electrical stimulation of those electrodes. Psychophysical and neurophysiological procedures were used to assess stimulus detection as a function of pulse rate under the various degrees of cochlear pathology. Cochlear morphology, assessed post-mortem, ranged from near-normal numbers of hair cells, peripheral processes and spiral ganglion cells, to complete absence of hair cells and peripheral processes and small numbers of surviving spiral ganglion cells. The psychophysical and neurophysiological studies indicated that slopes and levels of the threshold versus pulse rate functions reflected multipulse integration throughout the 200 ms pulse train with an additional contribution of interactions between adjacent pulses at high pulse rates. The amount of multipulse integration was correlated with the health of the implanted cochlea with implications for perception of more complex prosthetic stimuli.

Using the electrically-evoked compound action potential (ECAP) interphase gap effect to select electrode stimulation sites in cochlear implant users.

Studies in cochlear implanted animals show that the IPG Effect for ECAP growth functions (i.e., the magnitude of the change in ECAP amplitude growth function (AGF) slope or peak amplitude when the interphase gap (IPG) is increased) can be used to estimate the densities of spiral ganglion neurons (SGNs) near the electrode stimulation and recording sites. In humans, the same ECAP IPG Effect measures correlate with speech recognition performance. The present study examined the efficacy of selecting electrode sites for stimulation based on the IPG Effect, in order to improve performance of CI users on speech recognition tasks. We measured the ECAP IPG Effect for peak amplitude in adult (>18 years old) CI users (N= 18 ears), and created experimental programs to stimulate electrodes with either the highest or lowest ECAP IPG Effect for peak amplitude. Subjects also listened to a program without any electrodes deactivated. In a subset of subject ears (11/18), we compared performance differences between the experimental programs to post-operative computerized tomography (CT) scans to examine underlying factors that might contribute to the efficacy of an electrode site-selection approach. For sentences-in-noise, average performance was better when subjects listened to the experimental program that stimulated electrodes with the highest rather than the lowest IPG Effect for ECAP peak amplitude. A similar pattern was noted for transmission and perception of consonant place cues in a consonant recognition task. However, on average, performance when listening to a program with higher IPG Effect values was equal to that when listening with all electrodes activated. Results also suggest that scalar location (scala tympani or vestibuli) should be considered when using an ECAP-based electrode site-selection procedure to optimize CI performance.

Development of a chronically-implanted mouse model for studies of cochlear health and implant function.

Mice with chronic cochlear implants can significantly contribute to our understanding of the relationship between cochlear health and implant function because of the availability of molecular tools for controlling conditions in the cochlea and transgenic lines modeling human disease. To date, research in implanted mice has mainly consisted of short-term studies, but since there are large changes in implant function following implant insertion trauma, and subsequent recovery in many cases, longer-term studies are needed to evaluate function and perception under stable conditions. Because frequent anesthetic administration can be especially problematic in mice, a chronic model that can be tested in the awake condition is desirable. Electrically-evoked compound action potentials (ECAPs) recorded with multichannel cochlear implants are useful functional measures because they can be obtained daily without anesthesia. In this study, we assessed changes and stability of ECAPs, electrically-evoked auditory brainstem responses (EABRs), ensemble spontaneous activity (ESA), and impedance data over time after implanting mice with multichannel implants. We then compared these data to histological findings in these implanted cochleae, and compared results from this chronic mouse model to data previously obtained in a well-established chronically-implanted guinea pig model. We determined that mice can be chronically implanted with cochlear implants, and ECAP recordings can be obtained frequently in an awake state for up to at least 42 days after implantation. These recordings can effectively monitor changes or stability in cochlear function over time. ECAP and EABR amplitude-growth functions (AGFs), AGF slopes, ESA levels and impedances in mice with multichannel implants appear similar to those found in guinea pigs with long-term multichannel implants. Animals with better survival of spiral ganglion neurons (SGNs) and inner hair cells (IHCs) have steeper AGF slopes, and larger ESA responses. The time course of post-surgical ear recovery may be quicker in mice and can show different patterns of recovery which seem to be dependent on the degree of insertion trauma and subsequent histological conditions. Histology showed varying degrees of cochlear damage with fibrosis present in all implanted mouse ears and small amounts of new bone in a few ears. Impedance changes over time varied within and across animals and may represent changes over time in multiple variables in the cochlear environment post-implantation. Due to the small size of the mouse, susceptibility to stress, and the higher potential for implant failure, chronic implantation in mice can be challenging, but overall is feasible and useful for cochlear implant research.

Relationships between Intrascalar Tissue, Neuron Survival, and Cochlear Implant Function.

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.