Evaluating Changes in Adult Cochlear Implant Users' Brain and Behavior Following Auditory Training.

OBJECTIVES: To describe the effects of two types of auditory training on both behavioral and physiological measures of auditory function in cochlear implant (CI) users, and to examine whether a relationship exists between the behavioral and objective outcome measures. DESIGN: This study involved two experiments, both of which used a within-subject design. Outcome measures included behavioral and cortical electrophysiological measures of auditory processing. In Experiment I, 8 CI users participated in a music-based auditory training. The training program included both short training sessions completed in the laboratory as well as a set of 12 training sessions that participants completed at home over the course of a month. As part of the training program, study participants listened to a range of different musical stimuli and were asked to discriminate stimuli that differed in pitch or timbre and to identify melodic changes. Performance was assessed before training and at three intervals during and after training was completed. In Experiment II, 20 CI users participated in a more focused auditory training task: the detection of spectral ripple modulation depth. Training consisted of a single 40-minute session that took place in the laboratory under the supervision of the investigators. Behavioral and physiologic measures of spectral ripple modulation depth detection were obtained immediately pre- and post-training. Data from both experiments were analyzed using mixed linear regressions, paired t tests, correlations, and descriptive statistics. RESULTS: In Experiment I, there was a significant improvement in behavioral measures of pitch discrimination after the study participants completed the laboratory and home-based training sessions. There was no significant effect of training on electrophysiologic measures of the auditory N1-P2 onset response and acoustic change complex (ACC). There were no significant relationships between electrophysiologic measures and behavioral outcomes after the month-long training. In Experiment II, there was no significant effect of training on the ACC, although there was a small but significant improvement in behavioral spectral ripple modulation depth thresholds after the short-term training. CONCLUSIONS: This study demonstrates that auditory training improves spectral cue perception in CI users, with significant perceptual gains observed despite cortical electrophysiological responses like the ACC not reliably predicting training benefits across short- and long-term interventions. Future research should further explore individual factors that may lead to greater benefit from auditory training, in addition to optimization of training protocols and outcome measures, as well as demonstrate the generalizability of these findings.

Acoustic Change Complex Recorded in Hybrid Cochlear Implant Users.

INTRODUCTION: Expanding cochlear implant (CI) candidacy criteria and advances in electrode arrays and soft surgical techniques have increased the number of CI recipients who have residual low-frequency hearing. Objective measures such as obligatory cortical auditory-evoked potentials (CAEPs) may help clinicians make more tailored recommendations to recipients regarding optimal listening mode. As a step toward this goal, this study investigated how CAEPs measured from hybrid CI users differ in two listening modes: acoustic alone (A-alone) versus acoustic plus electric (A + E). METHODS: Eight successful hybrid CI users participated in this study. Two CAEPs, the P1-N1-P2 and the acoustic change complex (ACC), were measured simultaneously in response to the onset and change of a series of different and spectrally complex acoustic signals, in each of the two listening modes (A-alone and A + E). We examined the effects of listening mode and stimulus type on the onset and ACC N1-P2 amplitudes and peak latencies. RESULTS: ACC amplitudes in hybrid CI users significantly differed as a function of listening mode and stimulus type. ACC responses in A + E were larger than those in the A-alone mode. This was most evident for stimuli involving a change from low to high frequency. CONCLUSIONS: Results of this study showed that the ACC varies as a function of listening mode and stimulus type. This finding suggests that the ACC can be used as a physiologic, objective measure of the benefit of hybrid CIs, potentially supporting clinicians in making clinical recommendations on individualized listening mode, or to document subjective preference for a given listening mode. Further research into this potential clinical application in a range of hybrid recipients and/or long electrode users who have residual low-frequency hearing is warranted.

Longitudinal Electrocochleography as an Objective Measure of Serial Behavioral Audiometry in Electro-Acoustic Stimulation Patients.

OBJECTIVE: Minimally traumatic surgical techniques and advances in cochlear implant (CI) electrode array designs have allowed acoustic hearing present in a CI candidate prior to surgery to be preserved postoperatively. As a result, these patients benefit from combined electric-acoustic stimulation (EAS) postoperatively. However, 30% to 40% of EAS CI users experience a partial loss of hearing up to 30 dB after surgery. This additional hearing loss is generally not severe enough to preclude use of acoustic amplification; however, it can still impact EAS benefits. The use of electrocochleography (ECoG) measures of peripheral hair cell and neural auditory function have shed insight into the pathophysiology of postimplant loss of residual acoustic hearing. The present study aims to assess the long-term stability of ECoG measures and to establish ECoG as an objective method of monitoring residual hearing over the course of EAS CI use. We hypothesize that repeated measures of ECoG should remain stable over time for EAS CI users with stable postoperative hearing preservation. We also hypothesize that changes in behavioral audiometry for EAS CI users with loss of residual hearing should also be reflected in changes in ECoG measures. DESIGN: A pool of 40 subjects implanted under hearing preservation protocol was included in the study. Subjects were seen at postoperative visits for behavioral audiometry and ECoG recordings. Test sessions occurred 0.5, 1, 3, 6, 12 months, and annually after 12 months postoperatively. Changes in pure-tone behavioral audiometric thresholds relative to baseline were used to classify subjects into two groups: one group with stable acoustic hearing and another group with loss of acoustic hearing. At each test session, ECoG amplitude growth functions for several low-frequency stimuli were obtained. The threshold, slope, and suprathreshold amplitude at a fixed stimulation level was obtained from each growth function at each time point. Longitudinal linear mixed effects models were used to study trends in ECoG thresholds, slopes, and amplitudes for subjects with stable hearing and subjects with hearing loss. RESULTS: Preoperative, behavioral audiometry indicated that subjects had an average low-frequency pure-tone average (125 to 500 Hz) of 40.88 ± 13.12 dB HL. Postoperatively, results showed that ECoG thresholds and amplitudes were stable in EAS CI users with preserved residual hearing. ECoG thresholds increased (worsened) while ECoG amplitudes decreased (worsened) for those with delayed hearing loss. The slope did not distinguish between EAS CI users with stable hearing and subjects with delayed loss of hearing. CONCLUSIONS: These results provide a new application of postoperative ECoG as an objective tool to monitor residual hearing and understand the pathophysiology of delayed hearing loss. While our measures were conducted with custom-designed in-house equipment, CI companies are also designing and implementing hardware and software adaptations to conduct ECoG recordings. Thus, postoperative ECoG recordings can potentially be integrated into clinical practice.

RNA Interference Prevents Autosomal-Dominant Hearing Loss.

Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.

Relationship Between Peripheral and Psychophysical Measures of Amplitude Modulation Detection in Cochlear Implant Users.

OBJECTIVE: This study investigates the relationship between electrophysiological and psychophysical measures of amplitude modulation (AM) detection. Prior studies have reported both measures of AM detection recorded separately from cochlear implant (CI) users and acutely deafened animals, but no study has made both measures in the same CI users. Animal studies suggest a progressive loss of high-frequency encoding as one ascends the auditory pathway from the auditory nerve to the cortex. Because the CI speech processor uses the envelope of an ongoing acoustic signal to modulate pulse trains that are subsequently delivered to the intracochlear electrodes, it is of interest to explore auditory nerve responses to modulated stimuli. In addition, psychophysical AM detection abilities have been correlated with speech perception outcomes. Thus, the goal was to explore how the auditory nerve responds to AM stimuli and to relate those physiologic measures to perception. DESIGN: Eight patients using Cochlear Ltd. Implants participated in this study. Electrically evoked compound action potentials (ECAPs) were recorded using a 4000 pps pulse train that was sinusoidally amplitude modulated at 125, 250, 500, and 1000 Hz rates. Responses were measured for each pulse over at least one modulation cycle for an apical, medial, and basal electrode. Psychophysical modulation detection thresholds (MDTs) were also measured via a three-alternative forced choice, two-down, one-up adaptive procedure using the same modulation frequencies and electrodes. RESULTS: ECAPs were recorded from individual pulses in the AM pulse train. ECAP amplitudes varied sinusoidally, reflecting the sinusoidal variation in the stimulus. A modulated response amplitude (MRA) metric was calculated as the difference in the maximal and minimum ECAP amplitudes over the modulation cycles. MRA increased as modulation frequency increased, with no apparent cutoff (up to 1000 Hz). In contrast, MDTs increased as the modulation frequency increased. This trend is inconsistent with the physiologic measures. For a fixed modulation frequency, correlations were observed between MDTs and MRAs; this trend was evident at all frequencies except 1000 Hz (although only statistically significant for 250 and 500 Hz AM rates), possibly an indication of central limitations in processing of high modulation frequencies. Finally, peripheral responses were larger and psychophysical thresholds were lower in the apical electrodes relative to basal and medial electrodes, which may reflect better cochlear health and neural survival evidenced by lower preoperative low-frequency audiometric thresholds and steeper growth of neural responses in ECAP amplitude growth functions for apical electrodes. CONCLUSIONS: Robust ECAPs were recorded for all modulation frequencies tested. ECAP amplitudes varied sinusoidally, reflecting the periodicity of the modulated stimuli. MRAs increased as the modulation frequency increased, a trend we attribute to neural adaptation. For low modulation frequencies, there are multiple current steps between the peak and valley of the modulation cycle, which means successive stimuli are more similar to one another and neural responses are more likely to adapt. Higher MRAs were correlated with lower psychophysical thresholds at low modulation frequencies but not at 1000 Hz, implying a central limitation to processing of modulated stimuli.

Using Neural Response Telemetry to Monitor Physiological Responses to Acoustic Stimulation in Hybrid Cochlear Implant Users.

OBJECTIVE: This report describes the results of a series of experiments where we use the neural response telemetry (NRT) system of the Nucleus cochlear implant (CI) to measure the response of the peripheral auditory system to acoustic stimulation in Nucleus Hybrid CI users. The objectives of this study were to determine whether they could separate responses from hair cells and neurons and to evaluate the stability of these measures over time. DESIGN: Forty-four CI users participated. They all had residual acoustic hearing and used a Nucleus Hybrid S8, S12, or L24 CI or the standard lateral wall CI422 implant. The NRT system of the CI was used to trigger an acoustic stimulus (500-Hz tone burst or click), which was presented at a low stimulation rate (10, 15, or 50 per second) to the implanted ear via an insert earphone and to record the cochlear microphonic, the auditory nerve neurophonic and the compound action potential (CAP) from an apical intracochlear electrode. To record acoustically evoked responses, a longer time window than is available with the commercial NRT software is required. This limitation was circumvented by making multiple recordings for each stimulus using different time delays between the onset of stimulation and the onset of averaging. These recordings were then concatenated off-line. Matched recordings elicited using positive and negative polarity stimuli were added off-line to emphasize neural potentials (SUM) and subtracted off-line to emphasize potentials primarily generated by cochlear hair cells (DIF). These assumptions regarding the origin of the SUM and DIF components were tested by comparing the magnitude of these derived responses recorded using various stimulation rates. Magnitudes of the SUM and DIF components were compared with each other and with behavioral thresholds. RESULTS: SUM and DIF components were identified for most subjects, consistent with both hair cell and neural responses to acoustic stimulation. For a subset of the study participants, the DIF components grew as stimulus level was increased, but little or no SUM components were identified. Latency of the CAPs in response to click stimuli was long relative to reports in the literature of recordings obtained using extracochlear electrodes. This difference in response latency and general morphology of the CAPs recorded was likely due to differences across subjects in hearing loss configuration. The use of high stimulation rates tended to decrease SUM and CAP components more than DIF components. We suggest this effect reflects neural adaptation. In some individuals, repeated measures were made over intervals as long as 9 months. Changes over time in DIF, SUM, and CAP thresholds mirrored changes in audiometric threshold for the subjects who experienced loss of acoustic hearing in the implanted ear. CONCLUSIONS: The Nucleus NRT software can be used to record peripheral responses to acoustic stimulation at threshold and suprathreshold levels, providing a window into the status of the auditory hair cells and the primary afferent nerve fibers. These acoustically evoked responses are sensitive to changes in hearing status and consequently could be useful in characterizing the specific pathophysiology of the hearing loss experienced by this population of CI users.

Effects of Long-Term Musical Training on Cortical Auditory Evoked Potentials.

OBJECTIVE: Evidence suggests that musicians, as a group, have superior frequency resolution abilities when compared with nonmusicians. It is possible to assess auditory discrimination using either behavioral or electrophysiologic methods. The purpose of this study was to determine if the acoustic change complex (ACC) is sensitive enough to reflect the differences in spectral processing exhibited by musicians and nonmusicians. DESIGN: Twenty individuals (10 musicians and 10 nonmusicians) participated in this study. Pitch and spectral ripple discrimination were assessed using both behavioral and electrophysiologic methods. Behavioral measures were obtained using a standard three interval, forced choice procedure. The ACC was recorded and used as an objective (i.e., nonbehavioral) measure of discrimination between two auditory signals. The same stimuli were used for both psychophysical and electrophysiologic testing. RESULTS: As a group, musicians were able to detect smaller changes in pitch than nonmusician. They also were able to detect a shift in the position of the peaks and valleys in a ripple noise stimulus at higher ripple densities than non-musicians. ACC responses recorded from musicians were larger than those recorded from non-musicians when the amplitude of the ACC response was normalized to the amplitude of the onset response in each stimulus pair. Visual detection thresholds derived from the evoked potential data were better for musicians than non-musicians regardless of whether the task was discrimination of musical pitch or detection of a change in the frequency spectrum of the ripple noise stimuli. Behavioral measures of discrimination were generally more sensitive than the electrophysiologic measures; however, the two metrics were correlated. CONCLUSIONS: Perhaps as a result of extensive training, musicians are better able to discriminate spectrally complex acoustic signals than nonmusicians. Those differences are evident not only in perceptual/behavioral tests but also in electrophysiologic measures of neural response at the level of the auditory cortex. While these results are based on observations made from normal-hearing listeners, they suggest that the ACC may provide a non-behavioral method of assessing auditory discrimination and as a result might prove useful in future studies that explore the efficacy of participation in a musically based, auditory training program perhaps geared toward pediatric or hearing-impaired listeners.

Exploring the Source of Neural Responses of Different Latencies Obtained from Different Recording Electrodes in Cochlear Implant Users.

In this study we measured the electrically evoked compound action potential (ECAP) from different recording electrodes in the cochlea. Under the assumption that different response latencies may be the result of differences in the neural population contributing to the response, we assessed the relationship between neural response latency and spread of excitation. First, we evaluated changes in N1 latency when the recording electrode site was varied. Second, we recorded channel interaction functions using a forward masking technique but with recording electrodes at different intracochlear locations. For most individuals, N1 latency was similar across recording electrodes. However, reduced N1 latencies were observed in 21% of cochlear implant users when ECAPs were recorded using a remote recording electrode. We hypothesized that if recordings from different electrodes represented contributions from different populations of neurons, then one might expect that channel interaction functions would be different. However, we did not observe consistent differences in channel interaction functions (neither peak location nor breadth of the functions), and further, any variation in channel interaction functions was not correlated with ECAP latency. These results suggest that ECAPs from different recording electrodes with different latencies originate from similar neural populations.

Temporal Response Properties of the Auditory Nerve in Implanted Children with Auditory Neuropathy Spectrum Disorder and Implanted Children with Sensorineural Hearing Loss.

OBJECTIVE: This study aimed to (1) characterize temporal response properties of the auditory nerve in implanted children with auditory neuropathy spectrum disorder (ANSD), and (2) compare results recorded in implanted children with ANSD with those measured in implanted children with sensorineural hearing loss (SNHL). DESIGN: Participants included 28 children with ANSD and 29 children with SNHL. All subjects used cochlear nucleus devices in their test ears. Both ears were tested in 6 children with ANSD and 3 children with SNHL. For all other subjects, only one ear was tested. The electrically evoked compound action potential (ECAP) was measured in response to each of the 33 pulses in a pulse train (excluding the second pulse) for one apical, one middle-array, and one basal electrode. The pulse train was presented in a monopolar-coupled stimulation mode at 4 pulse rates: 500, 900, 1800, and 2400 pulses per second. Response metrics included the averaged amplitude, latencies of response components and response width, the alternating depth and the amount of neural adaptation. These dependent variables were quantified based on the last six ECAPs or the six ECAPs occurring within a time window centered around 11 to 12 msec. A generalized linear mixed model was used to compare these dependent variables between the 2 subject groups. The slope of the linear fit of the normalized ECAP amplitudes (re. amplitude of the first ECAP response) over the duration of the pulse train was used to quantify the amount of ECAP increment over time for a subgroup of 9 subjects. RESULTS: Pulse train-evoked ECAPs were measured in all but 8 subjects (5 with ANSD and 3 with SNHL). ECAPs measured in children with ANSD had smaller amplitude, longer averaged P2 latency and greater response width than children with SNHL. However, differences in these two groups were only observed for some electrodes. No differences in averaged N1 latency or in the alternating depth were observed between children with ANSD and children with SNHL. Neural adaptation measured in these 2 subject groups was comparable for relatively short durations of stimulation (i.e., 11 to 12 msec). Children with ANSD showed greater neural adaptation than children with SNHL for a longer duration of stimulation. Amplitudes of ECAP responses rapidly declined within the first few milliseconds of stimulation, followed by a gradual decline up to 64 msec after stimulus onset in the majority of subjects. This decline exhibited an alternating pattern at some pulse rates. Further increases in pulse rate diminished this alternating pattern. In contrast, ECAPs recorded from at least one stimulating electrode in six ears with ANSD and three ears with SNHL showed a clear increase in amplitude over the time course of stimulation. The slope of linear regression functions measured in these subjects was significantly greater than zero. CONCLUSIONS: Some but not all aspects of temporal response properties of the auditory nerve measured in this study differ between implanted children with ANSD and implanted children with SNHL. These differences are observed for some but not all electrodes. A new neural response pattern is identified. Further studies investigating its underlying mechanism and clinical relevance are warranted.

Relationships Among Peripheral and Central Electrophysiological Measures of Spatial and Spectral Selectivity and Speech Perception in Cochlear Implant Users.

OBJECTIVES: The ability to perceive speech is related to the listener's ability to differentiate among frequencies (i.e., spectral resolution). Cochlear implant (CI) users exhibit variable speech-perception and spectral-resolution abilities, which can be attributed in part to the extent of electrode interactions at the periphery (i.e., spatial selectivity). However, electrophysiological measures of peripheral spatial selectivity have not been found to correlate with speech perception. The purpose of this study was to evaluate auditory processing at the periphery and cortex using both simple and spectrally complex stimuli to better understand the stages of neural processing underlying speech perception. The hypotheses were that (1) by more completely characterizing peripheral excitation patterns than in previous studies, significant correlations with measures of spectral selectivity and speech perception would be observed, (2) adding information about processing at a level central to the auditory nerve would account for additional variability in speech perception, and (3) responses elicited with spectrally complex stimuli would be more strongly correlated with speech perception than responses elicited with spectrally simple stimuli. DESIGN: Eleven adult CI users participated. Three experimental processor programs (MAPs) were created to vary the likelihood of electrode interactions within each participant. For each MAP, a subset of 7 of 22 intracochlear electrodes was activated: adjacent (MAP 1), every other (MAP 2), or every third (MAP 3). Peripheral spatial selectivity was assessed using the electrically evoked compound action potential (ECAP) to obtain channel-interaction functions for all activated electrodes (13 functions total). Central processing was assessed by eliciting the auditory change complex with both spatial (electrode pairs) and spectral (rippled noise) stimulus changes. Speech-perception measures included vowel discrimination and the Bamford-Kowal-Bench Speech-in-Noise test. Spatial and spectral selectivity and speech perception were expected to be poorest with MAP 1 (closest electrode spacing) and best with MAP 3 (widest electrode spacing). Relationships among the electrophysiological and speech-perception measures were evaluated using mixed-model and simple linear regression analyses. RESULTS: All electrophysiological measures were significantly correlated with each other and with speech scores for the mixed-model analysis, which takes into account multiple measures per person (i.e., experimental MAPs). The ECAP measures were the best predictor. In the simple linear regression analysis on MAP 3 data, only the cortical measures were significantly correlated with speech scores; spectral auditory change complex amplitude was the strongest predictor. CONCLUSIONS: The results suggest that both peripheral and central electrophysiological measures of spatial and spectral selectivity provide valuable information about speech perception. Clinically, it is often desirable to optimize performance for individual CI users. These results suggest that ECAP measures may be most useful for within-subject applications when multiple measures are performed to make decisions about processor options. They also suggest that if the goal is to compare performance across individuals based on a single measure, then processing central to the auditory nerve (specifically, cortical measures of discriminability) should be considered.

Peripheral and Central Contributions to Cortical Responses in Cochlear Implant Users.

OBJECTIVES: The primary goal of this study was to describe relationships between peripheral and central electrophysiologic measures of auditory processing within individual cochlear implant (CI) users. The distinctiveness of neural excitation patterns resulting from the stimulation of different electrodes, referred to as 'spatial selectivity,' was evaluated. The hypothesis was that if central representations of spatial interactions differed across participants semi-independently of peripheral input, then the within-subject relationships between peripheral and central electrophysiologic measures of spatial selectivity would reflect those differences. Cross-subject differences attributable to processing central to the auditory nerve may help explain why peripheral electrophysiologic measures of spatial selectivity have not been found to correlate with speech perception. DESIGN: Eleven adults participated in this and a companion study. All were peri- or post-lingually deafened with more than 1 year of CI experience. Peripheral spatial selectivity was evaluated at 13 cochlear locations using 13 electrodes as probes to elicit electrically evoked compound action potentials (ECAPs). Masker electrodes were varied across the array for each probe electrode to derive channel-interaction functions. The same 13 electrodes were used to evaluate spatial selectivity represented at a cortical level. Electrode pairs were stimulated sequentially to elicit the auditory change complex (ACC), an obligatory cortical potential suggestive of discrimination. For each participant, the relationship between ECAP channel-interaction functions (quantified as channel-separation indices) and ACC N1-P2 amplitudes was modeled using the saturating exponential function y = a * (1-e). Both a and b coefficients were varied using a least-squares approach to optimize the fits. RESULTS: Electrophysiologic measures of spatial selectivity assessed at peripheral (ECAP) and central (ACC) levels varied across participants. The results indicate that differences in ACC amplitudes observed across participants for the same stimulus conditions were not solely the result of differences in peripheral excitation patterns. This finding supports the view that processing at multiple points along the auditory neural pathway from the periphery to the cortex may vary across individuals with different etiologies and auditory experiences. CONCLUSIONS: The distinctiveness of neural excitation resulting from electrical stimulation varies across CI recipients, and this variability was observed in both peripheral and cortical electrophysiologic measures. The ACC amplitude differences observed across participants were partially independent from differences in peripheral neural spatial selectivity. These findings are clinically relevant because they imply that there may be limits (1) to the predictive ability of peripheral measures and (2) in the extent to which improving the selectivity of electrical stimulation via programming options (e.g., current focusing/steering) will result in more specific central neural excitation patterns or will improve speech perception.

Cortical Auditory Evoked Potentials Recorded From Nucleus Hybrid Cochlear Implant Users.

OBJECTIVES: Nucleus Hybrid Cochlear Implant (CI) users hear low-frequency sounds via acoustic stimulation and high-frequency sounds via electrical stimulation. This within-subject study compares three different methods of coordinating programming of the acoustic and electrical components of the Hybrid device. Speech perception and cortical auditory evoked potentials (CAEP) were used to assess differences in outcome. The goals of this study were to determine whether (1) the evoked potential measures could predict which programming strategy resulted in better outcome on the speech perception task or was preferred by the listener, and (2) CAEPs could be used to predict which subjects benefitted most from having access to the electrical signal provided by the Hybrid implant. DESIGN: CAEPs were recorded from 10 Nucleus Hybrid CI users. Study participants were tested using three different experimental processor programs (MAPs) that differed in terms of how much overlap there was between the range of frequencies processed by the acoustic component of the Hybrid device and range of frequencies processed by the electrical component. The study design included allowing participants to acclimatize for a period of up to 4 weeks with each experimental program prior to speech perception and evoked potential testing. Performance using the experimental MAPs was assessed using both a closed-set consonant recognition task and an adaptive test that measured the signal-to-noise ratio that resulted in 50% correct identification of a set of 12 spondees presented in background noise. Long-duration, synthetic vowels were used to record both the cortical P1-N1-P2 "onset" response and the auditory "change" response (also known as the auditory change complex [ACC]). Correlations between the evoked potential measures and performance on the speech perception tasks are reported. RESULTS: Differences in performance using the three programming strategies were not large. Peak-to-peak amplitude of the ACC was not found to be sensitive enough to accurately predict the programming strategy that resulted in the best performance on either measure of speech perception. All 10 Hybrid CI users had residual low-frequency acoustic hearing. For all 10 subjects, allowing them to use both the acoustic and electrical signals provided by the implant improved performance on the consonant recognition task. For most subjects, it also resulted in slightly larger cortical change responses. However, the impact that listening mode had on the cortical change responses was small, and again, the correlation between the evoked potential and speech perception results was not significant. CONCLUSIONS: CAEPs can be successfully measured from Hybrid CI users. The responses that are recorded are similar to those recorded from normal-hearing listeners. The goal of this study was to see if CAEPs might play a role either in identifying the experimental program that resulted in best performance on a consonant recognition task or in documenting benefit from the use of the electrical signal provided by the Hybrid CI. At least for the stimuli and specific methods used in this study, no such predictive relationship was found.

Optimizing the combination of acoustic and electric hearing in the implanted ear.

OBJECTIVES: The aim of this study was to determine an optimal approach to program combined acoustic plus electric (A+E) hearing devices in the same ear to maximize speech-recognition performance. DESIGN: Ten participants with at least 1 year of experience using Nucleus Hybrid (short electrode) A+E devices were evaluated across three different fitting conditions that varied in the frequency ranges assigned to the acoustically and electrically presented portions of the spectrum. Real-ear measurements were used to optimize the acoustic component for each participant, and the acoustic stimulation was then held constant across conditions. The lower boundary of the electric frequency range was systematically varied to create three conditions with respect to the upper boundary of the acoustic spectrum: Meet, Overlap, and Gap programming. Consonant recognition in quiet and speech recognition in competing-talker babble were evaluated after participants were given the opportunity to adapt by using the experimental programs in their typical everyday listening situations. Participants provided subjective ratings and evaluations for each fitting condition. RESULTS: There were no significant differences in performance between conditions (Meet, Overlap, Gap) for consonant recognition in quiet. A significant decrement in performance was measured for the Overlap fitting condition for speech recognition in babble. Subjective ratings indicated a significant preference for the Meet fitting regimen. CONCLUSIONS: Participants using the Hybrid ipsilateral A+E device generally performed better when the acoustic and electric spectra were programmed to meet at a single frequency region, as opposed to a gap or overlap. Although there is no particular advantage for the Meet fitting strategy for recognition of consonants in quiet, the advantage becomes evident for speech recognition in competing-talker babble and in patient preferences.

Preliminary results of the relationship between the binaural interaction component of the electrically evoked auditory brainstem response and interaural pitch comparisons in bilateral cochlear implant recipients.

OBJECTIVE: : The purpose of this study was to investigate the relationship between electrophysiologic measures of the binaural interaction component (BIC) of the electrically evoked auditory brainstem response and psychophysical measures of interaural pitch comparisons in Nucleus bilateral cochlear implant users. DESIGN: : Data were collected for 10 postlingually deafened adult cochlear implant users. Each subject conducted an interaural pitch-comparison task using a biphasic pulse train with a pulse rate of 1000 pulses per second (pps) at high stimulation levels. Stimuli were presented in a two-interval, two-alternative forced-choice procedure with roving current variations. A subgroup of four subjects repeated the task at low stimulation levels. BICs were measured using loudness balanced, biphasic current pulses presented at a rate of 19.9 pps for each subject by pairing the electrode 12 (out of 22 intracochlear electrodes) in the right ear with each of 11 electrodes spaced across the electrode array in the left ear. The BIC was measured at high stimulation levels in 10 subjects and at low stimulation levels in 7 subjects. Because of differences in stimulation rate used in BIC measures and interaural pitch comparisons, the actual stimulation levels were different in these two measures. The relationship between BIC responses and results of interaural pitch comparisons was evaluated for each of the individual subjects and at the group level. Evaluation was carried out separately for results obtained at high and low stimulation levels. RESULTS: : There was no significant correlation between results of BIC measures and interaural pitch comparisons on either the individual or group levels. Lower stimulation level did not improve the relationship between these two measures. CONCLUSIONS: : No significant correlations between psychophysical measures of interaural pitch comparisons and electrophysiologic measures of the BIC of the electrically evoked auditory brainstem response were found. The lack of correlation may be attributed to methods used to quantify the data, small number of subjects retested at low stimulation levels, and central processing components involved in the interaural pitch-comparison task.

Access and Polarization Electrode Impedance Changes in Electric-Acoustic Stimulation Cochlear Implant Users with Delayed Loss of Acoustic Hearing.

Acoustic hearing can be preserved after cochlear implant (CI) surgery, allowing for combined electric-acoustic stimulation (EAS) and superior speech understanding compared to electric-only hearing. Among patients who initially retain useful acoustic hearing, 30-40 % experience a delayed hearing loss that occurs 3 or more months after CI activation. Increases in electrode impedances have been associated with delayed loss of residual acoustic hearing, suggesting a possible role of intracochlear inflammation/fibrosis as reported by Scheperle et al. (Hear Res 350:45-57, 2017) and Shaul et al. (Otol Neurotol 40(5):e518-e526, 2019). These studies measured only total impedance. Total impedance consists of a composite of access resistance, which reflects resistance of the intracochlear environment, and polarization impedance, which reflects resistive and capacitive properties of the electrode-electrolyte interface as described by Dymond (IEEE Trans Biomed Eng 23(4):274-280, 1976) and Tykocinski et al. (Otol Neurotol 26(5):948-956, 2005). To explore the role of access and polarization impedance components in loss of residual acoustic hearing, these measures were collected from Nucleus EAS CI users with stable acoustic hearing and subsequent precipitous loss of hearing. For the hearing loss group, total impedance and access resistance increased over time while polarization impedance remained stable. For the stable hearing group, total impedance and access resistance were stable while polarization impedance declined. Increased access resistance rather than polarization impedance appears to drive the increase in total impedances seen with loss of hearing. Moreover, access resistance has been correlated with intracochlear fibrosis/inflammation in animal studies as observed by Xu et al. (Hear Res 105(1-2):1-29, 1997) and Tykocinski et al. (Hear Res 159(1-2):53-68, 2001). These findings thus support intracochlear inflammation as one contributor to loss of acoustic hearing in our EAS CI population.

Residual Hair Cell Responses in Electric-Acoustic Stimulation Cochlear Implant Users with Complete Loss of Acoustic Hearing After Implantation.

Changes in cochlear implant (CI) design and surgical techniques have enabled the preservation of residual acoustic hearing in the implanted ear. While most Nucleus Hybrid L24 CI users retain significant acoustic hearing years after surgery, 6-17 % experience a complete loss of acoustic hearing (Roland et al. Laryngoscope. 126(1):175-81. (2016), Laryngoscope. 128(8):1939-1945 (2018); Scheperle et al. Hear Res. 350:45-57 (2017)). Electrocochleography (ECoG) enables non-invasive monitoring of peripheral auditory function and may provide insight into the pathophysiology of hearing loss. The ECoG response is evoked using an acoustic stimulus and includes contributions from the hair cells (cochlear microphonic-CM) as well as the auditory nerve (auditory nerve neurophonic-ANN). Seven Hybrid L24 CI users with complete loss of residual hearing months after surgery underwent ECoG measures before and after loss of hearing. While significant reductions in CMs were evident after hearing loss, all participants had measurable CMs despite having no measurable acoustic hearing. None retained measurable ANNs. Given histological data suggesting stable hair cell and neural counts after hearing loss (e.g., Quesnel et al. Hear Res. 333:225-234. (2016)), the loss of ECoG and audiometric hearing may reflect reduced synaptic input. This is consistent with the theory that residual CM responses coupled with little to no ANN responses reflect a "disconnect" between hair cells and auditory nerve fibers (Fontenot et al. Ear Hear. 40(3):577-591. 2019). This "disconnection" may prevent proper encoding of auditory stimulation at higher auditory pathways, leading to a lack of audiometric responses, even in the presence of viable cochlear hair cells.

Effects of stimulation level and electrode pairing on the binaural interaction component of the electrically evoked auditory brain stem response.

OBJECTIVES: The purpose of this study was to investigate the effects of stimulation level and electrode pairing on the binaural interaction component (BIC) of the electrically evoked auditory brain stem response (EABR) in Nucleus cochlear implant (CI) users. DESIGN: Ten postlingually deafened adult CI users participated in this study. EABRs were measured using loudness balanced, biphasic current pulses presented in the left monaural, right monaural, and bilateral stimulation conditions. BICs were computed based on measures of the EABR obtained for each subject by pairing the electrode 12 (of 22 intracochlear electrodes) in the right ear with each of 11 electrodes spaced across the electrode array in the left ear. The effect of stimulation level on the amplitude of the BIC was investigated by measuring growth functions of the BIC from six subjects. The effect of electrode pairing on the amplitude of the BIC was studied at high stimulation levels in 10 subjects and at low stimulation levels in seven subjects. The high stimulation level was chosen as the 90% point of the subject's dynamic range (DR) or the highest stimulation level in which the electrophysiologic recordings were not contaminated by muscle artifacts. The low stimulation level was chosen as a level that was 10% point of subject's DR higher than the BIC threshold for six of these seven subjects. For one subject, BIC thresholds were not available and the low stimulation level was referred to the 70% point of subject's DR. RESULTS: BICs were successfully recorded from all 11 interaural electrode pairs for a majority of subjects tested at both stimulation levels. BIC amplitudes increased with stimulation level. The effect of stimulation level on latencies of the BIC was less robust. At high stimulation levels, BIC amplitudes did not change significantly as the stimulating electrode used in the left ear was systematically varied. When low stimulation levels were used, BIC amplitude was maximal for interaural electrode pairs with similar intracochlear positions and decreased when the offset between interaural electrodes increased. CONCLUSIONS: This study demonstrates that stimulation level affects amplitudes of the BIC response. It is possible to record the BIC of the EABR in bilateral CI users even from interaural electrode pairs that have large interaural offsets. This finding suggests that when high-level stimuli are used, there is a broad pattern of current spread within the two cochleae. At lower stimulation levels, the spread of excitation within the cochlea is reduced making the effect of electrode pairing on the amplitude of the BIC more pronounced.

Effects of long-term use of a cochlear implant on the electrically evoked compound action potential.

BACKGROUND: Since the early 1990s, it has been possible to measure electrically evoked compound action potentials (ECAPs) from Nucleus cochlear implant users. Recording the ECAP does not require active participation by the subject, and the recordings are not adversely affected by attention or sleep, making this response an ideal tool for monitoring long-term changes. Previous research from our laboratory (Hughes et al, 2001) has shown that ECAP thresholds and slope of the ECAP growth functions are relatively stable over time. However, this conclusion was based on results obtained from a fairly limited number of study participants, each of whom used the Nucleus CI24M cochlear implant and were followed for less than two years. PURPOSE: To evaluate the effect of long-term use of a cochlear implant on ECAP thresholds and slope of the ECAP input/output function for both pediatric and adult cochlear implant recipients. RESEARCH DESIGN: A longitudinal study that describes how ECAP thresholds and growth functions change over a period of 96 mo following initial activation. Changes over time in ECAP threshold and slope of the ECAP growth function were analyzed, and effects of the subject's age, type of CI (cochlear implant), and stimulating electrode are included in the analysis. STUDY SAMPLE: 134 Nucleus CI users participated in this study. All were profoundly deaf. This subject pool included 84 individuals (40 adults and 44 children) who used the Nucleus CI24M cochlear implant and 50 individuals (21 adults and 29 children) who used the Nucleus CI24R cochlear implant. DATA COLLECTION AND ANALYSIS: Electrodes 5, 10, 15, and 20 were stimulated, and ECAP growth functions were measured for each subject at regular intervals following the initial activation of the device. RESULTS: Small increases in mean ECAP thresholds were observed for both pediatric and adult CI users between an "early" visit that occurred within 3-6 mo following hookup and a "late" visit that occurred 4.8-6 yr later. For adults, the average increase in ECAP threshold was 3.94 CL (clinical programming units for Nucleus CIs). For children, the average increase was 4.16 CL. These differences, while small, were statistically significant. Slope of the ECAP growth functions measured over the same time interval did not change significantly. On average, pediatric CI users had ECAP thresholds that were 4-5 CL units higher than the adult CI recipients. The most striking outcome from this study, however, was the finding that when compared with postlingually deafened adults, pediatric CI users had ECAP growth functions that were substantially steeper. The differences between the results obtained from children and those obtained from adults were statistically significant and largely independent of device type or stimulating electrode. CONCLUSION: Results from this study show ECAP thresholds and growth functions to change very little over a 5-6 yr observation interval suggesting that long-term use of a CI is not likely to have a significant negative impact on the response of the peripheral auditory system. Pediatric CI users were shown to have, on average, higher ECAP thresholds and steeper ECAP growth functions than postlingually deafened adult CI users. This finding suggests potential differences between the two patient populations either in terms of the current fields within the cochlea or the effective distance between the stimulating electrode and the stimulable neural tissue.

Comparison of electrically evoked compound action potential thresholds and loudness estimates for the stimuli used to program the Advanced Bionics cochlear implant.

BACKGROUND: In the mid-1990s, Cochlear Corporation introduced a cochlear implant (CI) to the market that was equipped with hardware that made it possible to record electrically evoked compound action potentials (ECAPs) from CI users of all ages. Over the course of the next decade, many studies were published that compared ECAP thresholds with levels used to program the speech processor of the Nucleus CI. In 2001 Advanced Bionics Corporation introduced the Clarion CII cochlear implant (the Clarion CII internal device is also known as the CII Bionic Ear). This cochlear implant was also equipped with a system that allowed measurement of the ECAP. While a great deal is known about how ECAP thresholds compare with the levels used to program the speech processor of the Nucleus CI, relatively few studies have reported comparisons between ECAP thresholds and the levels used to program the speech processor of the Advanced Bionics CI. PURPOSE: To explore the relationship between ECAP thresholds and behavioral measures of perceptual dynamic range for the range of stimuli commonly used to program the speech processor of the Advanced Bionics CI. RESEARCH DESIGN: This prospective and experimental study uses correlational and descriptive statistics to define the relationship between ECAP thresholds and perceptual dynamic range measures. STUDY SAMPLE: Twelve postlingually deafened adults participated in this study. All were experienced users of the Advanced Bionics CI system. DATA COLLECTION AND ANALYSIS: ECAP thresholds were recorded using the commercially available SoundWave software. Perceptual measures of threshold (T-level), most comfortable level (M-level), and maximum comfortable level (C-level) were obtained using both "tone bursts" and "speech bursts." The relationship between these perceptual and electrophysiological variables was defined using paired t-tests as well as correlation and linear regression. RESULTS: ECAP thresholds were significantly correlated with the perceptual dynamic range measures studied; however, correlations were not strong. Analysis of the individual data revealed considerable discrepancy between the contour of ECAP threshold versus electrode function and the behavioral loudness estimates used for programming. CONCLUSION: ECAP thresholds recorded from Advanced Bionics cochlear implant users always indicated levels where the programming stimulus was audible for the listener. However, the correlation between ECAP thresholds and M-levels (the primary metric used to program the speech processor of the Advanced Bionics CI), while statistically significant, was quite modest. If programming levels are to be determined on the basis of ECAP thresholds, care should be taken to ensure that stimulation is not uncomfortably loud, particularly on the basal electrodes in the array.

Pilot Evaluation of Sheep as In Vivo Model for Cochlear Implantation.

OBJECTIVES: The rise in the use of cochlear implants (CIs) has continued to fuel research aimed at improving surgical approaches and the preservation of residual hearing. Current in vivo models involve small animals not suitable for evaluating full-sized CIs nor are prohibitively expensive nonhuman primates. The objective of this study was to develop and evaluate an in vivo model of cochlear implantation in sheep. METHODS: Eight adult, female sheep were implanted with full-sized CIs from three manufacturers using a retrofacial approach to the round window. Partial electrode insertions were performed to a depth of 10 to 12 mm before closure. Round window electrocochleography (ECoG) and auditory brainstem responses (ABR) were conducted during and after surgery. Following a 30-day implantation, cochleae were explanted and imaged using both x-ray microscopy and histology. RESULTS: The surgery was well tolerated although limited complications were observed in three of eight sheep. Electrode insertions were up to 12 mm before insertion resistance noted. ECoG and ABR responses were reduced postimplantation, reflecting changes in cochlear mechanics due to the presence of the implant, and/or insertion trauma. Histological and radiological image analysis showed the presence of intracochlear fibrosis as well as one instance of tip fold-over. CONCLUSIONS: The use of sheep presents a feasible live-animal model to study cochlear implantations. Full-sized implants as well as surgical techniques can be evaluated on functional outcomes such as ABR and ECoG as well as histological markers for residual hearing including intracochlear fibrosis. Use of this model and surgical approach has potential to evaluate CIs and surgical techniques in both the acute and chronic setting.