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.

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.

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.

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.

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.

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.

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.

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.

Effects of Electrode Location on Estimates of Neural Health in Humans with Cochlear Implants.

There are a number of psychophysical and electrophysiological measures that are correlated with SGN density in animal models, and these same measures can be performed in humans with cochlear implants (CIs). Thus, these measures are potentially applicable in humans for estimating the condition of the neural population (so called "neural health" or "cochlear health") at individual sites along the electrode array and possibly adjusting the stimulation strategy in the CI sound processor accordingly. Some measures used to estimate neural health in animals have included the electrically evoked compound potential (ECAP), psychophysical detection thresholds, and multipulse integration (MPI). With regard to ECAP measures, it has been shown that the change in the ECAP response as a function of increasing the stimulus interphase gap ("IPG Effect") also reflects neural density in implanted animals. These animal studies have typically been conducted using preparations in which the electrode was in a fixed position with respect to the neural population, whereas in human cochlear implant users, the position of individual electrodes varies widely within an electrode array and also across subjects. The current study evaluated the effects of electrode location in the implanted cochlea (specifically medial-lateral location) on various electrophysiological and psychophysical measures in eleven human subjects. The results demonstrated that some measures of interest, specifically ECAP thresholds, psychophysical detection thresholds, and ECAP amplitude-growth function (AGF) linear slope, were significantly related to the distances between the electrode and mid-modiolar axis (MMA). These same measures were less strongly related or not significantly related to the electrode to medial wall (MW) distance. In contrast, neither the IPG Effect for the ECAP AGF slope or threshold, nor the MPI slopes were significantly related to MMA or MW distance from the electrodes. These results suggest that "within-channel" estimates of neural health such as the IPG Effect and MPI slope might be more suitable for estimating nerve condition in humans for clinical application since they appear to be relatively independent of electrode position.

Changes over time in the electrically evoked compound action potential (ECAP) interphase gap (IPG) effect following cochlear implantation in Guinea pigs.

The electrically-evoked compound action potential (ECAP) is correlated with spiral ganglion neuron (SGN) density in cochlear implanted animals. In a previous study, we showed that ECAP amplitude growth function (AGF) linear slopes for stimuli with a constant interphase gap (IPG) changed significantly over time following implantation. Related studies have also shown that 1) IPG sensitivity for ECAP measures ("IPG Effect") is related to SGN density in animals and 2) the ECAP IPG Effect is related to speech recognition performance in humans with cochlear implants. The current study examined how the ECAP IPG Effect changed following cochlear implantation in four non-deafened guinea pigs with residual inner hair cells (IHCs) and 5 deafened, neurotrophin-treated guinea pigs. Simple impedances were measured on the same days as the ECAP measures. Generally, non-deafened implanted animals with higher SGN survival demonstrated higher ECAP AGF linear slope and peak amplitude values than the deafened, implanted guinea pigs. The ECAP IPG Effect for the AGF slopes and peak amplitudes was also larger in the hearing animals. The N1 latencies for a constant IPG were not different between groups, but the N1 latency IPG Effect was smaller in the non-deafened, implanted animals. Similar to previously reported results, ECAP measures using a fixed or changing IPG required as many as three months after implantation before a stable point could be calculated, but this was dependent on the animal and condition. For all ECAP measures most animals showed greater variance in the first 30 days post-implantation. Post-implantation changes in ECAPs and impedances were not correlated with one another. Results from this study are helpful for estimating the mechanisms underlying ECAP characteristics and have implications for clinical application of the ECAP measures in long-term human cochlear implant recipients. Specifically, these measures could help to monitor neural health over a period of time, or during a time of stability these measures could be used to help select electrode sites for activation in clinical programming.

Voltage readout from a piezoelectric intracochlear acoustic transducer implanted in a living guinea pig.

The ability to measure the voltage readout from a sensor implanted inside the living cochlea enables continuous monitoring of intracochlear acoustic pressure locally, which could improve cochlear implants. We developed a piezoelectric intracochlear acoustic transducer (PIAT) designed to sense the acoustic pressure while fully implanted inside a living guinea pig cochlea. The PIAT, fabricated using micro-electro-mechanical systems (MEMS) techniques, consisted of an array of four piezoelectric cantilevers with varying lengths to enhance sensitivity across a wide frequency bandwidth. Prior to implantation, benchtop tests were conducted to characterize the device performance in air and in water. When implanted in the cochlea of an anesthetized guinea pig, the in vivo voltage response from the PIAT was measured in response to 80-95 dB sound pressure level 1-14 kHz sinusoidal acoustic excitation at the entrance of the guinea pig's ear canal. All sensed signals were above the noise floor and unaffected by crosstalk from the cochlear microphonic or external electrical interference. These results demonstrate that external acoustic stimulus can be sensed via the piezoelectric voltage response of the implanted MEMS transducer inside the living cochlea, providing key steps towards developing intracochlear acoustic sensors to replace external or subcutaneous microphones for auditory prosthetics.

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.

Neurotrophin Gene Therapy in Deafened Ears with Cochlear Implants: Long-term Effects on Nerve Survival and Functional Measures.

Because cochlear implants function by stimulating the auditory nerve, it is assumed that the condition of the nerve plays an important role in the efficacy of the prosthesis. Thus, considerable research has been devoted to methods of preserving the nerve following deafness. Neurotrophins have been identified as a potential contributor to neural health, but most of the research to date has been done in young animals and for short periods (less than 3 to 6 months) after the onset of treatment. The first objective of the current experiment was to examine the effects of a neurotrophin gene therapy delivery method on spiral ganglion neuron (SGN) preservation and function in the long term (5 to 14 months) in mature guinea pigs with cochlear implants. The second objective was to examine several potential non-invasive monitors of auditory nerve health following the neurotrophin gene therapy procedure. Eighteen mature adult male guinea pigs were deafened by cochlear perfusion of neomycin and then one ear was inoculated with an adeno-associated viral vector with an Nft3-gene insert (AAV.Ntf3) and implanted with a cochlear implant electrode array. Five control animals were deafened and inoculated with an empty AAV and implanted. Data from 43 other guinea pig ears from this and previous experiments were used for comparison: 24 animals implanted in a hearing ear, nine animals deafened and implanted with no inoculation, and ten normal-hearing non-implanted ears. After 4 to 21 months of psychophysical and electrophysiological testing, the animals were prepared for histological examination of SGN densities and inner hair cell (IHC) survival. Seventy-eight percent of the ears deafened and inoculated with AAV.Ntf3 showed better SGN survival than the 14 deafened-control ears. The degree of SGN preservation following the gene therapy procedure was variable across animals and across cochlear turns. Slopes of psychophysical multipulse integration (MPI) functions were predictive of SGN density, but only in animals with preserved IHCs. MPI was not affected by the AAV.Ntf3 treatment, but there was a minor improvement in temporal integration (TI). AAV.Ntf3 treatment had significant effects on ECAP and EABR amplitude growth func-tion (AGF) slopes; the reduction in slope in deafened ears was ameliorated by the AAV.Ntf3 treatment. Slopes of the ECAP and EABR AGFs were predictive of SGN density in a broad area near and just apical to the implant. The highest ensemble spontaneous activity (ESA) values were seen in animals with surviving IHCs, but AAV.Ntf3 treatment in deafened ears resulted in slightly higher ESA values compared to deafened untreated ears. Overall, a combination of the psychophysical and electrophysiological measures can be useful for monitoring the health of the implanted cochlea in guinea pigs. These measures should be applicable for assessing cochlear health in human subjects.

Effects of electrode deactivation on speech recognition in multichannel cochlear implant recipients.

OBJECTIVES: The objective of the current study is to evaluate how speech recognition performance is affected by the number of active electrodes that are turned off in multichannel cochlear implants. Several recent studies have demonstrated positive effects of deactivating stimulation sites based on an objective measure in cochlear implant processing strategies. Previous studies using an analysis of variance have shown that, on average, cochlear implant listeners' performance does not improve beyond eight active electrodes. We hypothesized that using a generalized linear mixed model would allow for better examination of this question. METHODS: Seven peri- and post-lingual adult cochlear implant users (eight ears) were tested on speech recognition tasks using experimental MAPs which contained either 8, 12, 16 or 20 active electrodes. Speech recognition tests included CUNY sentences in speech-shaped noise, TIMIT sentences in quiet as well as vowel (CVC) and consonant (CV) stimuli presented in quiet and in signal-to-noise ratios of 0 and +10 dB. RESULTS: The speech recognition threshold in noise (dB SNR) significantly worsened by approximately 2 dB on average as the number of active electrodes was decreased from 20 to 8. Likewise, sentence recognition scores in quiet significantly decreased by an average of approximately 12%. DISCUSSION/CONCLUSION: Cochlear implant recipients can utilize and benefit from using more than eight spectral channels when listening to complex sentences or sentences in background noise. The results of the current study suggest a conservative approach for turning off stimulation sites is best when using site-selection procedures.

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.

Across-site patterns of electrically evoked compound action potential amplitude-growth functions in multichannel cochlear implant recipients and the effects of the interphase gap.

Electrically evoked compound action potential (ECAP) measures of peak amplitude, and amplitude-growth function (AGF) slope have been shown to reflect characteristics of cochlear health (primarily spiral ganglion density) in anesthetized cochlear-implanted guinea pigs. Likewise, the effect of increasing the interphase gap (IPG) in each of these measures also reflects SGN density in the implanted guinea pig. Based on these findings, we hypothesize that suprathreshold ECAP measures, and also how they change as the IPG is increased, have the potential to be clinically applicable in human subjects. However, further work is first needed in order to determine the characteristics of these measures in humans who use cochlear implants. The current study examined across-site patterns of suprathreshold ECAP measures in 10 bilaterally-implanted, adult cochlear implant users. Results showed that both peak amplitude and slope of the AGF varied significantly from electrode to electrode in ear-specific patterns across the subjects' electrode arrays. As expected, increasing the IPG on average increased the peak amplitude and slope. Across ears, there was a significant, negative correlation between the slope of the ECAP AGF and the duration of hearing loss. Across-site patterns of ECAP peak amplitude and AGF slopes were also compared with common ground impedance values and significant correlations were observed in some cases, depending on the subject and condition. The results of this study, coupled with previous studies in animals, suggest that it is feasible to measure the change in suprathreshold ECAP measures as the IPG increases on most electrodes. Further work is needed to investigate the relationship between these measures and cochlear implant outcomes, and determine how these measures might be used when programming a cochlear-implant processor.

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.

Insertion trauma and recovery of function after cochlear implantation: Evidence from objective functional measures.

Partial loss and subsequent recovery of cochlear implant function in the first few weeks following cochlear implant surgery has been observed in previous studies using psychophysical detection thresholds. In the current study, we explored this putative manifestation of insertion trauma using objective functional measures: electrically-evoked compound action potential (ECAP) amplitude-growth functions (ECAP amplitude as a function of stimulus level). In guinea pigs implanted in a hearing ear with good post-implant hearing and good spiral ganglion neuron (SGN) survival, consistent patterns of ECAP functions were observed. The slopes of ECAP growth functions were moderately steep on the day of implant insertion, decreased to low levels over the first few days after implantation and then increased slowly over several weeks to reach a relatively stable level. In parallel, ECAP thresholds increased over time after implantation and then recovered, although more quickly, to a relatively stable low level as did thresholds for eliciting a facial twitch. Similar results were obtained in animals deafened but treated with an adenovirus with a neurotrophin gene insert that resulted in good SGN preservation. In contrast, in animals implanted in deaf ears that had relatively poor SGN survival, ECAP slopes reached low levels within a few days after implantation and remained low. These results are consistent with the idea that steep ECAP growth functions require a healthy population of auditory nerve fibers and that cochlear implant insertion trauma can temporarily impair the function of a healthy SGN population.