Psychoacoustic and electrophysiological electric-acoustic interaction effects in cochlear implant users with ipsilateral residual hearing

Hearing Research 386 (2020) 107873

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Psychoacoustic and electrophysiological electric-acoustic interaction effects in cochlear implant users with ipsilateral residual hearing Marina Imsiecke a, Andreas Büchner a, b, Thomas Lenarz a, b, Waldo Nogueira a, b, * a b

Department of Otorhinolaryngology, Hannover Medical School, Hanover, Germany Cluster of Excellence ‘Hearing4All’, Hanover, Germany

a r t i c l e i n f o

a b s t r a c t

Article history: Received 8 October 2019 Received in revised form 9 December 2019 Accepted 10 December 2019 Available online 18 December 2019

Cochlear implant users with ipsilateral residual hearing combine acoustic and electric hearing in one ear, this is called electric-acoustic stimulation (EAS). In EAS users, masking can be shown for electric probes in the presence of acoustic maskers and vice versa. Masking effects in acoustic hearing are generally attributed to nonlinearities of the basilar membrane and hair cell adaptation effects. However, similar masking patterns are observed more centrally in electric hearing. Consequently, there is no consensus so far on the level of interaction between the two modalities. Animal studies have shown that electricacoustic interaction effects can result in reduced physiological responses in the cochlear nerve and the inferior colliculus. In CI users with residual hearing, it has recently become feasible to record intracochlear potentials with a high spatial resolution via the implanted electrode array. An investigation of the electrophysiological effects during combined electric-acoustic stimulation in humans might be used to assess peripheral mechanisms of masking. Seventeen MED-EL Flex electrode users with ipsilateral residual hearing participated in both a behavioral and a physiological electric-acoustic masking experiment. Psychoacoustic methods were used to measure the changes in behavioral thresholds due to the presence of a masker of the opposing modality. Subjects were stimulated electrically with unmodulated pulse trains using a research interface and acoustically with pure tones delivered via headphones. Auditory response telemetry was used to obtain objective electrophysiological changes of electrically evoked compound action potential and electrocochleography for electric, acoustic and combined electric-acoustic presentation in the same subjects. Behavioral thresholds of probe tones, either electric or acoustic, were significantly elevated in the presence of acoustic or electric maskers, respectively. 15 subjects showed significant electric threshold elevation with acoustic masking that did not depend on the electric-acoustic frequency difference (EAFD), a measure for the proximity of stimulation sites in the cochlea. Electric masking showed significant threshold elevation in eleven subjects, which depended significantly on EAFD. In the electrophysiological masking experiment, reduced responses to electric and acoustic stimulation with additional stimulation of the opposing modality were observed. Results showed a similar asymmetry as the psychoacoustic masking experiment. Response reduction was smaller than threshold elevation, especially for electric masking. Some subjects showed reduced responses to acoustic stimulation with electric masking, especially for small EAFD. The reduction of electrically evoked responses was significant in some subjects. No correlation was observed between psychoacoustic and electrophysiological masking results. From present study, it can be concluded that both electric and acoustic stimulation mask each other when presented simultaneously. Electrophysiological measurements indicate that masking effects are already to some extent present in the periphery. © 2019 Elsevier B.V. All rights reserved.

Keywords: Electric-acoustic stimulation Electrophysiological masking Electrocochleography (ECochG) Difference response Electrically evoked compound action potential (ECAP)

* Corresponding author. Department of Otorhinolaryngology, Hannover Medical School, Hanover, Germany. E-mail addresses: [email protected], [email protected] (M. Imsiecke), [email protected] (A. Büchner), lenarz. [email protected] (T. Lenarz), [email protected] (W. Nogueira). https://doi.org/10.1016/j.heares.2019.107873 0378-5955/© 2019 Elsevier B.V. All rights reserved.

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M. Imsiecke et al. / Hearing Research 386 (2020) 107873

Abbreviations ECAP ECochG CI DIF EAFD EAS SUM

electrically evoked compound action potential electrocochleography cochlear implant difference potential electric-acoustic frequency difference electric-acoustic stimulation sum potential

1. Introduction Electric-acoustic stimulation (EAS) has become a treatment option for patients that suffer from severe-to-profound hearing loss in high frequencies but retain a significant hearing in low frequencies (Fraysse et al., 2006). These patients can be implanted with short, atraumatic electrode arrays, substituting the natural hearing in high frequencies while preserving to a great extent the residual hearing in more apical regions of the cochlea (Gantz and Turner, 2003; Lenarz et al., 2009, 2013). This low-frequency hearing can be enhanced with acoustic amplification, delivered through a hearing aid that is included in the traditional speech processor of the cochlear implant (CI) (Turner et al., 2008). EAS systems combine the electric stimulation of a traditional CI with the acoustic stimulation of a traditional hearing aid (von Ilberg et al., 1999). Patients using these devices have been found to benefit greatly from the additional low-frequency information, by being able to more naturally perceive speech (Dorman et al., 2008; Gantz et al., 2005), speaker characteristics (Turner et al., 2004) and even music (Gfeller et al., 2006; Turner et al., 2008). They exhibit benefits especially in adverse listening conditions such as speech in noise (Büchner et al., 2009; Gantz et al., 2009; Turner et al., 2004, 2008), indicating that the preservation of residual hearing is very advantageous. Several studies have shown that electric and acoustic stimulation interact and change behavioral thresholds for simultaneous (Krüger et al., 2017; Lin et al., 2011) or non-simultaneous stimulation (Imsiecke et al., 2018). A first study investigated a systematic programming method that takes into account the electric-acoustic masking effects (Imsiecke et al., 2019). It could be shown that with an overlapping frequency range of electric and acoustic stimulation, masking effects limit speech reception outcomes. Also, a masking adjusted fitting, aimed at reducing interaction effects, showed an improvement in speech reception thresholds in individual subjects. However, the time required to conduct psychoacoustic masking experiments and their subjective nature constitute a serious disadvantage for their use in the clinical routine. To reduce measurement durations and objectively determine electric-acoustic interaction, electrophysiological measurements, such as electrocochleography (ECochG) and electrically evoked compound action potentials (ECAP), have been proposed. Previous studies employed the backward telemetry of the CI to objectively measure electrophysiological responses to acoustic and electric stimulation and to estimate the changes of these responses elicited by combined electric-acoustic stimulation (Koka and Litvak, 2017; Krüger et al., under review). They showed the interaction of electric-acoustic stimulation by measuring the reduction of ECochG amplitude due to additional electric pulse train stimulation. In the present study, ECochG measurements are conducted in MED-EL implant users and reported for electric-acoustic stimulation in this population. Peripheral responses to acoustic tones and electric single pulses are obtained. By calculating the difference

response (DIF), i.e. the difference of the electrophysiological potential to acoustic stimulation with positive and negative leading phase, the components of the cochlear microphonics elicited by hair cells are emphasized (Aran and Charlet de Sauvage, 1976; Patuzzi et al., 1989). This emphasis of cochlear microphonics by the DIF potential could be reduced with the presence of high-frequency hearing loss, as the DIF potential also contains a strong component of the auditory nerve neurophonic for low-frequency acoustic stimuli at high stimulus levels (Forgues et al., 2014). However, the assessment of the DIF potential is useful for investigating the different mechanisms of peripheral interaction of electric and acoustic stimulation. It can be compared with the sum potential (SUM), which consists of the non-linear proportion of the hair cell and auditory nerve responses (Forgues et al., 2014). Electrophysiological studies in animals have shown the feasibility of objective measurements for the characterization of electric-acoustic interaction (Miller et al., 2009; Nourski et al., 2005; Stronks et al., 2010, 2012). These studies used the electrically or acoustically evoked compound action potential (ECAP/CAP) in implanted animals with residual hearing. Stronks et al. (2012) reported a significant reduction of ECAP amplitude with additional acoustic stimulation for normal hearing animals and broadband or high-level low-frequency noise stimulation. For higher levels of noise, animals with a high-frequency hearing loss also exhibited suppression of ECAP responses. Nourski et al. (2005) reported the greatest effects of suppression for high electric and acoustic stimulus levels. Electrophonic interaction, caused either by the electric stimulation of outer hair cells, resulting in a traveling wave, or by the change of membrane potential of inner hair cells, is hypothesized to be partially responsible for the observed electricacoustic interaction effects (Stronks et al., 2013). In humans, electric-acoustic interaction could occur at different stages of the auditory pathway. These stages could be identified by the different components of both ECochG and ECAP, with the objective to distinguish the effect of electric-acoustic stimulation on hair cells and auditory nerve. As noted before, the ECochG can be used to estimate the components of hair cells and auditory nerve and will be used to investigate the effect of electric stimulation on their acoustically elicited responses. The acoustic masking of electric stimulation is investigated by measuring the changes in electrically evoked potentials (ECAP) caused by additional acoustic stimulation, which has not been reported in humans. In this study, electric-acoustic interaction effects are investigated in subjects with various degrees of electrode array insertion depth and different amounts of residual hearing. Results gathered through behavioral threshold experiments regarding acoustic-onelectric masking are reported. Furthermore results of electric-onacoustic masking, partially published in Imsiecke et al. (2019), are recaptured. They are compared to the results obtained from electrophysiological interaction experiments performed by measuring ECochG and ECAP responses towards combined electric and acoustic stimulation. A change in electrophysiological responses between isolated and combined electric and acoustic stimulation would be an indication of peripheral effects of electric-acoustic interaction. This work aims at investigating the underlying mechanisms that explain the origin of masking between electric and acoustic stimulation, as currently there is no consensus on the mechanisms of electric-acoustic interaction in humans. Furthermore, the hypothesis, whether behavioral psychoacoustic masking experiments correlate to objective measurements of interaction, is tested. This would allow an assessment of the feasibility of an objective tool to estimate electric-acoustic interaction, which could be used in the clinical routine.

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2. Experimental methods 2.1. Subjects 17 CI users, which had been implanted after a post-lingual severe high-frequency hearing loss, were invited to participate in this study. They were implanted with MED-EL electrodes of the FlexSeries (Flex28, Flex24, Flex20 or the Hanover Custom Made Device Flex16), some only partially (Lenarz et al., 2019), and all had residual acoustic hearing at low frequencies. The amount of residual hearing for each of the 17 subjects is shown in Fig. 1 with clinical pure-tone audiograms. The demographic data for the study participants is given in Table 1. The median age of participants was 50 years, and 11 right ears and 7 left ears were measured. All subjects gave written informed consent to the experiment as approved by the Hannover Medical School’s institutional review board. 15 subjects had already participated in the speech reception measurement experiment, published in Imsiecke et al. (2019). To ease comparability the IDs were kept and the two additional subjects received ID numbers 16 and 17. Measurement time for each subject for psychoacoustic measurements was six to 7 h, divided into two appointments, and for the electrophysiological experiment was around 3 h. 2.2. Psychoacoustic masking experiment The psychoacoustic masking experiment of the present study has been in part published in Imsiecke et al. (2019), and will be compared with new data of electrophysiological measurements. The setup used for stimulation in this experiment is explained in greater detail in Krüger et al. (2017). 2.2.1. Stimuli Electric and acoustic stimuli were presented during this experiment, either as maskers or as probes. Maskers were 500 ms and probes were 20 ms long and controlled in Matlab (The MathWorks Inc., Massachusetts, USA). Electric stimuli were 1000 pulses per second pulse trains of biphasic pulses with 33 ms phase duration

Fig. 1. Clinical audiograms of all study participants at time of testing. The measurement of the hearing level of subject ID3 at 3 kHz was not available.

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and an interphase gap of 2.1 ms? They were stimulated directly through a research interface (MED-EL RIB2 interface). Acoustic stimuli were generated by a NI-DAQ card (National Instruments, Austin, Texas, USA) and delivered via Sennheiser HDA-200 headphones (Sennheiser electronic GmbH & Co. KG, Wedemark, Germany) connected to a headphone amplifier (Lake People electronic GmbH, Konstanz, Germany). Acoustic stimulation was calibrated €er, Nærum, with an artificial ear and level meter (Brüel & Kja Denmark). Synchrony between electric and acoustic stimulation was obtained by a trigger out signal of the research interface connected to a trigger in channel of the NI-DAQ card. 2.2.2. Procedure Initially, loudness balancing was obtained in order to ensure the masker stimuli were all presented at equally perceived loudness levels. For this, two steps of a self-adjustment procedure are conducted. In the first step the subject was instructed to use a rotating endless encoder (Griffin Powermate, Griffin Technology, Tennessee, USA) to adjust the volume of the masker tone to “just perceivable”, “most comfortably loud” and “upper comfortable loudness level”, using a ten-interval loudness scale. This first estimate of the most comfortable level is then used as a starting point for the accurate loudness balancing procedure. In this second step, two adjacent stimuli (pulse trains or pure tones) are balanced in loudness twice by keeping one tone fixed and adjusting the second in amplitude until it sounds equally loud. The adjustment begins once 10% below the first most comfortable loud estimate of the adjustable tone by an ascending run and once from 10% above most or at upper comfortable level with a descending run. The end values of the two runs are averaged and taken as the balanced level. This is continued in a paired comparison until all frequencies or electrodes used in the experiment are covered. Only after the initial balancing of loudness for all electrodes and frequencies the psychoacoustic experiment was started. In this experiment, perception thresholds of the stimuli were measured. A 3-interval 2-alternative forced-choice paradigm with a 2-down 1up stepping rule in order to estimate the 71% point on the psychometric function (Levitt, 1971) was used to estimate the behavioral threshold and its standard deviation, as described in Krüger et al. (2017) and Imsiecke et al. (2018). If the standard deviation exceeded 4 dB for acoustic and 1 dB for electric probes, the corresponding threshold estimate was repeated. Unmasked threshold measurements were repeated in order to obtain more reliable results for the estimation of threshold elevation. The test-retest variability for repeated threshold estimates was 2.91 dB for acoustic thresholds and 0.41 dB for electric thresholds. In one subject it was not possible to determine some electric masked thresholds due to masking effects greater than the possible initial level of the acoustic probe (upper comfortable level). The subject was instructed to repeat the task for at least 20 presentations of that combination of electrode and acoustic frequency and to guess at the right answer. As the paradigm will not easily converge with only chance performance, the run was aborted if after these 20 presentations the subject still reported to not be able to detect the test tone and performed below or at chance level. The corresponding threshold was set to maximum level. 2.2.3. Data analysis Unmasked and masked thresholds were subtracted to obtain threshold elevation for each combination of masker and probe. Krüger et al. (2017) introduced the electric-acoustic frequency difference (EAFD) measurement which is included to interpret the obtained data concerning the stimulation site of electric and acoustic stimuli. The frequency map of Stakhovskaya et al. (2007) was used to assign place frequencies to insertion angles. The

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Table 1 Subject data with subject number (ID), gender, side of implantation, age at testing for present study, duration of implant use, etiology of deafness in implanted ear, electrode type, with partial insertion (PI) and angle of insertion depth with the corresponding place frequency according to Stakhovskaya et al. (2007). Subject ID

Gender

Side

Age [years]

CI use [years]

Electrode type

Insertion depth [
]

Place Frequency [Hz]

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

f f m f f m f f f f m f m m m f f

l r l r l r r l r l l l r r r r r

46 43 62 44 52 48 46 39 49 68 71 56 61 63 62 34 50

1.7 0.9 2.6 2.2 1.6 1.4 1.5 1.9 2.9 2.7 1.5 2.0 1.7 2.7 1.5 3,3 2,5

Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex Flex

242 316 220 217 254 237 324 342 347 220 192 444 346 348 532 286 360

2000 1044 2388 2446 1781 2072 984 762 745 2388 2937 450 850 840 352 1335 785

latter were obtained for all electrodes from cone beam computer tomography available from clinical imaging. Threshold elevation results are consequently plotted over the EAFD for all subjects to ensure comparability independent of cochlear geometry and electrode length. An EAFD below zero corresponds to acoustic frequencies whose tonotopy is located more basally than the estimated place frequency of the electrode. 2.3. Electrophysiological masking experiment Electrophysiological experiments via the implanted Flex (MEDEL Medical Electronics, Innsbruck, Austria) electrode array with acoustic stimulation have been conducted in EAS users before, to identify changes in response strength during and after implantation (Haumann et al., 2019). In this work, this subject population is for the first time investigated with combined electric-acoustic stimulation, to identify the interaction between the two stimulation modalities in the periphery of the auditory pathway. 2.3.1. Stimuli Short electric and acoustic stimuli were presented during the electrophysiological measurement. Single electric biphasic pulses of 33 ms duration and 2.1 ms interphase gap were stimulated via direct coupling of the implant. They were controlled by the Evoked Potential Tool and delivered through a MAX-Box (both MED-EL Medical Electronics, Innsbruck, Austria). This setup also recorded the evoked intracochlear potentials through the implant, to assess electrically evoked compound action potentials (ECAP) and electrocochleography (ECochG). External acoustic stimulation was delivered at different audiometric frequencies that were found to show interaction effects in the psychoacoustic measurement. Acoustic tone bursts of 16 ms duration were ramped with cosine ramps of 4 ms duration and presented with positive and negative polarity. They were generated by a NI-DAQ sound card (National Instruments, Austin, Texas, USA) and delivered via 3M E-A-R-Tone Gold insert earphones (Auditory Systems, Indianapolis, USA) connected to a headphone amplifier (Lake People electronic GmbH, Konstanz, Germany). Amplification of acoustic stimulation was €er, calibrated with an artificial ear and levelmeter (Brüel & Kja Nærum, Denmark). Synchrony between electric and acoustic stimulation was obtained by a trigger out signal of the research interface connected to a trigger in channel of the audio card. In order to receive maximal responses of the auditory nerve and residual hair cells, stimulation of electric pulses and acoustic tone

24 20 16 16 16 16 28 28 20 16 24 24 24 20 28 16 20

PI

PI PI

PI

bursts was set to maximally acceptable loudness levels. It was estimated by an up-down procedure, where the stimulus level is increased until the subject reported it as uncomfortably loud and then is reduced until it is declared as acceptable. Acoustic tone bursts and electric single pulses were adjusted in this way. 2.3.2. Recording procedure The software EP Tool measures electrophysiological potentials at a defined electrode and thus obtains either ECAP or ECochG measurements, depending on the mode of stimulation and analysis (see Haumann et al., 2019). If the electric stimulation current is set above zero, a biphasic pulse is delivered to the selected electrode with the defined configuration. Artifact reduction is built into the software and achieved by a forward masking paradigm using the measurement of four conditions ‘masker’, ‘probe’, ‘masker and probe’ as well as ‘noise’ (Miller et al., 2000). Furthermore, the length of the buffer (1.7 ms) is extended by sampling the measurement interval (19.4 ms) through delayed but overlapping measurements. The resulting evoked potential trace, which is calculated as an average of all repetitions of the measurement interval, is stored into memory. As a trigger is emitted for each measurement interval, it is possible to include additional external acoustic stimulation. For the acoustic condition, single measurements are conducted for each of the two leading phases of acoustic stimulation, rarefaction and condensation, and stored in different traces. Additionally, for every electrode, a noise measurement with no acoustic stimulation is conducted. Electric stimulation was delivered on the three most apical electrodes (numbers 1 to 3) and recorded on the adjacent electrode in the apical direction. Only for stimulus electrode #2 the recording electrode was #1. The body of the implant serves as the reference electrode for the backward telemetry measurement and the data was sampled at a rate of 118 kHz and a maximum recording window of 19 ms. During electrophysiological data collection, study participants were allowed to read, occupy themselves (e.g. knit) or watch muted, captioned movies. 2.3.3. Data analysis Intracochlear potential recordings were obtained for electric, acoustic and electric-acoustic stimulation and were analyzed separately for components of the electric and acoustic stimulation. All raw traces were exported from the Evoked Potential Tool and analyzed offline in custom MATLAB scripts. Resulting changes in thresholds and responses were analyzed for statistical significance

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using two-sided Wilcoxon signed-rank tests, to infer whether thresholds or response strengths are different for combined than for individual presentation. These tests were applied for all measured combinations across subjects and within subjects so that they were considered significant, if p lay below 0.05. Electrically evoked response: Recordings obtained after electric pulse stimulation were repeated twice (amounting to 200 averages) and the mean was calculated to obtain the ECAP. The mean trace was analyzed in the time domain by measuring the amplitude of the ECAP from the first negative peak N1 to the following positive peak P2. To obtain the interaction, a derived electric (Der E) response was obtained by subtracting the acoustic (A) response from the electricacoustic (E þ A) trace, with acoustic stimulation presented both with a leading positive and negative polarity. For exemplary traces see Fig. 7. Acoustically evoked response: Raw waveforms of ECochG measurements for acoustic stimulation of different polarity (rarefaction/negative leading, condensation/positive leading) were stored individually. Differentiation of the two waveforms gives the difference potential (DIF), which is assumed to contain mostly cochlear microphonics, i.e. hair cell responses (Dallos et al., 1974). Summation, on the other hand, yields the sum potential (SUM), which has been argued to contain mostly neural responses (Snyder and Schreiner, 1984). Even though Forgues et al. (2014) argued that hair cell and auditory nerve responses cannot be isolated due to nonlinearities particularly at high stimulation levels and low frequencies, SUM and DIF are investigated for changes due to additional electric stimulation. The characteristics were quantified using a digital Fourier transform of the SUM and DIF traces after applying zero padding and a Blackman-Harris window. The spectral component corresponding to the stimulation frequency, as well as its second and third harmonic (e.g. 500 Hz, 1000 Hz and 1500 Hz for a tone burst of 500 Hz), were identified. A peak analysis was performed, and peaks were classified as significant if they exceeded the noise floor by three standard deviations. The noise floor mean and variance were estimated from the six neighboring frequency bins around the peak frequency (Forgues et al., 2014). The magnitude of this peak in relation to 1 mV is calculated in dB. Responses towards acoustic (A) and derived acoustic (Der A), which was obtained by subtracting the electric (E) response from electricacoustic (E þ A) stimulation traces, were analyzed in this manner and changes in spectral peaks calculated in dB. For exemplary traces see Fig. 5.

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of threshold elevation (p < 0.0005). Of the 17 subjects, 11 subjects showed significant threshold elevation on an individual level with a highest median threshold elevation of 14 dB in subject ID 11, as shown in Table 2. For subjects IDs 5, 7, 10, 13, 15 and 16 the threshold elevation was not significant. It seemed to vary around zero and stayed within the test-retest variability even for a small EAFD. 3.1.2. Acoustic masking In the psychoacoustic acoustic masking experiment, threshold elevation of electric probes was measured under the presence of acoustic stimulation. Table 2 presents the individual median values and statistics of threshold elevation with a Wilcoxon signed rank test across all tested combinations. Again, a great variety of electrodes and frequencies were tested for the masking experiment, thus results are shown as a function of EAFD in Fig. 2 (right). 15 of the 17 subjects showed significant threshold elevation, as shown in Table 2, with the highest threshold elevation of 2.63 dB observed in subject ID 3. Overall threshold elevation was less strong than for electric masking, with a mean elevation of electric probes of 1.25 ± 1.21 dB and median 1.02 dB (p < 0.0005) and a broader distribution of elevated thresholds across EAFD. Two subjects (IDs 12 and 13) did not show significant threshold elevation, with threshold elevation varying around zero across all measured EAFD. 3.2. Electrophysiological results

3.1. Psychoacoustic experiment

3.2.1. Electrocochleography with acoustic stimulation Acoustically evoked peripheral potentials of the residual hearing of EAS implantees were used to investigate the effect of electricacoustic interaction. In a preliminary analysis, however, they can be analyzed for their amplitude across frequencies and recording electrodes in single subjects. An example of a measurement in a subject with very high ECochG amplitudes for different recording electrodes and stimulation at 2000 Hz is shown in Fig. 3. Both stimulation phases (positive and negative leading) are shown. The highest amplitude can be observed at the recording electrode # 5, decaying towards more basal and more apical electrodes. A decrease in latency can also be observed. The ECochG amplitudes for all measurements across all subjects, frequencies and recording electrodes are shown in Fig. 4 in dB relative to 1 mV. Only significant peaks are shown, resulting in a reduced number of measurements for the SUM amplitude, which estimates the auditory nerve component. The DIF and SUM amplitudes are shown as a function of the EAFD of the combination of frequency and recording electrode. A peak in the amplitude for an EAFD of around one octave can be observed for both DIF and SUM amplitudes, with much smaller amplitudes in the SUM potentials.

3.1.1. Electric masking In the psychoacoustic electric masking experiment, threshold elevation of acoustic probes was measured under the presence of electric stimulation. Table 2 presents the individual median values and statistics of threshold elevation across all tested combinations. Significance was tested with a Wilcoxon signed-rank test (p < 0.05) for individual and for all subjects. As a great variety of electrodes and frequencies were tested for the masking experiment, results are shown as a function of the electric-acoustic frequency difference (EAFD) as defined by Krüger et al. (2017) (Fig. 2 left). The minimum EAFD tested for each study participant is given in Table 2. The individual electric masking results of 15 of the 17 subjects (IDs 1 to 15) that participated in the current study have been published in Imsiecke et al. (2019) and are also shown in Table 2. Overall, masked thresholds were significantly elevated over unmasked thresholds, with mean 3.47 ± 6.51 dB and median 1.5 dB

3.2.2. Acoustic response reduction by additional electric stimulation Response potentials were measured with acoustic and electricacoustic stimulation. Two phases of acoustic stimuli were presented, leading positive (i.e. condensation) and leading negative (rarefaction). For the assessment of electric-acoustic interaction, the analysis of the SUM potential proved to be not feasible, as the response was below or at noise floor for most subjects and frequencies. This is represented Fig. 4 by the reduced number of significant frequency peaks. Thus, only very few interaction measurements could be gained for the SUM measurement, which did not allow for a thorough analysis and are thus not shown here. The DIF potential elicited by acoustic and electric-acoustic stimulation was chosen to be investigated for signs of peripheral interaction. The derived acoustic (Der A) response was obtained by subtracting the electric response from the electric-acoustic response. An example of the analysis of acoustic response

3. Results

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Table 2 Median values and p statistics of psychophysical threshold elevation and electrophysiological response reduction of electric and acoustic masking, p values obtained with twosided Wilcoxon signed rank test. Mean values for subjects 1 to 15 for acoustic threshold elevation can be found in Imsiecke et al. (2019). Missing subjects in the electric masking condition did not show significant acoustic responses, so no response reduction could be observed. EAFDmin indicates the minimum EAFD measured for the different combinations of electric and acoustic stimulation. Subj. ID

EAFDmin

Acoustic Threshold elevation [dB]

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 All

0.01 0.06 0.30 0.29 0.83 0.05 0.98 0.20 0.83 0.26 0.97 0.17 0.77 0.75 0.49 0.17 1.35

1.50 1.00 11.00 3.75 3.25 2.13 0.75 2.25 2.88 0.50 14.00 1.00 1.00 1.75 1.50 1.00 2.00 1.50

p 0.012 0.041 <0.001 <0.001 0.065 0.001 0.742 0.001 <0.001 0.591 0.002 0.046 0.085 0.010 0.205 0.113 0.004 <0.001

Electric

Response reduction [dB]

p

1.02 2.09 0.70 3.13

0.625 0.500 1.000 0.125

2.97

0.031

1.46 5.31 0.69 1.06 2.31

0.016 0.063 0.188 0.063 1.000

3.33 2.64 0.62 5.86 1.54

0.125 1.000 1.000 0.125 <0.001

reduction is shown in Fig. 5 for an exemplary subject. The left upper figure shows the measured potentials for acoustic and electricacoustic stimulation with both phases of acoustic stimulation. The strong electric evoked component is visible in the electric-acoustic stimulation potential (colored). The obtained DIF potential responses of acoustic (A) and derived acoustic (Der A) response (bottom left) are then analyzed for their spectral components (top right) and significant peaks are identified. The reduction of the spectral amplitude of the harmonic components is then calculated in dB for all combinations of stimulus frequency and masker electrode. Positive values indicate a decrease in response (bottom right). An analysis of the effect of stimulation at a specific electrode on different frequencies for all subjects is shown in Fig. 6. In most cases, the response reduction is small, but electrode #2 elicits a reduction in response of more than 6 dB for two subjects. If depicted across the EAFD (Fig. 9), a tendency of higher interaction for an EAFD of 1 octave can be observed. The statistical assessment of overall response reduction showed a significant effect with a

Threshold elevation [dB] 1.59 0.94 2.63 2.59 0.55 1.29 0.55 0.63 2.31 0.39 2.12 0.63 0.08 0.31 0.89 2.12 1.88 1.02

p <0.001 <0.001 0.002 <0.001 0.005 <0.001 0.031 0.001 <0.001 0.001 0.031 0.235 0.583 0.039 0.003 0.031 <0.001 <0.001

Response reduction [dB] 0.60 0.03 0.30 0.27 0.06 0.07 0.39 0.38 0.50 1.26 0.16 0.01 0.24 1.61 1.29 2.71 0.17 0.21

p 0.750 0.844 0.250 0.438 0.313 0.031 0.156 0.156 0.031 0.125 0.063 0.625 0.219 0.063 0.125 0.125 0.375 <0.001

median acoustic response reduction of 1.54 dB (p ¼ 0.0006, mean 2.33 ± 2.59 dB). Subjects ID 4, 9, 14 and 17 showed the highest reduction of acoustic responses as averaged over all frequencies and masker electrodes. Significant response changes were observed in ID 6 and 8, even though they showed less change in acoustic response. However, ss only a limited number of valid measurements could be obtained for each subject, a statistical analysis on an individual subject level failed to convey the whole picture. Even though the pattern of the observed electrophysiological masking resembles that of the psychoacoustic masking pattern, no correlation was found. This is evident in subjects ID 3 and 11 who exhibit the highest threshold elevation, but only very low response reduction. Acoustic response reduction was significantly, but mildly correlated to the amplitude of the acoustic response (R2 ¼ 0.24, p ¼ 0.02). 3.2.3. Electric response reduction by additional acoustic stimulation Electrically elicited response potentials were measured with

Fig. 2. Threshold elevation in dB over electric-acoustic frequency difference (EAFD) for electric masking of acoustic probe tones (left) and acoustic masking on electric probe tones (right) for all subjects.

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Fig. 3. Electrophysiological potential with acoustic stimulation of different phases for subject ID 6 showing the behavior across the electrode array.

electric and acoustic-electric stimulation. Acoustic stimulation started 5 ms before the stimulation of the electric pulse and was presented simultaneously. From observations in normal hearing animals (McAnally et al., 1997) the anticipation of an electrophonic hair cell response in subjects with very good residual hearing (e.g. ID 1) seemed plausible. However, neither the traces nor the spectral analysis of the electric and derived electric condition, showed signs of electrically evoked hair cell responses. Consequently, the potential response towards the electric stimulation was analyzed through the amplitude of the ECAP. An example trace and analysis of the ECAP measurement is shown in Fig. 7 for ID 8. The strong N1 and P2 components are visible in both electric (E) and acoustic-electric (A þ E) stimulation (Fig. 7A), with the acoustically elicited opposing oscillations visible shortly after the ECAP. The summation of the two phases of acoustic-electric (rarefaction and condensation of acoustic stimulus) traces cancels out most of the hair cell components, and leaves the ECAP, as the electric pulse was always anodic first. The

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resulting trace of the derived electric (Der E) response was obtained by subtracting the summed acoustic traces from the summed acoustic-electric traces (Fig. 7A). It was analyzed for a reduction in amplitude in the scale of dB (Fig. 7B). The reduction is shown for the combinations of different stimulus electrodes and masker frequencies, and for the respective EAFD. The analysis of the ECAP reduction caused by additional acoustic stimulation of different masker frequencies in each individual electrode is shown in Fig. 8. For most tested combinations, ECAP reduction is above zero but small, with the highest values of ECAP reduction in subject ID 14. ECAP reduction does not show a clear dependency on frequency or stimulus electrode, which is also found across EAFD, as shown in Fig. 9 (right). However, a statistical assessment of masking across EAFD showed a highly significant reduction across all subjects of median 0.21 dB (p < 0.001, mean 0.48 ± 0.89 dB) and a significant reduction in two subjects (p < 0.05, IDs 6 and 9). Highest values of median response reduction were observed in subjects IDs 14 and 16. However, due to the limited amount of tested combinations per subject, the power of the statistical tests is low and significance cannot easily be detected. An asymmetry to the acoustic response reduction is observed in electrophysiological masking, similarly to psychoacoustic masking. A reduced effect strength and broad shape across EAFD is found for acoustic masking. Again, a correlation between acoustic response reduction and threshold elevation was not found. Electric response reduction however showed an inverse correlation to the strength of the ECAP component with R2 ¼ 0.32 (p ¼ 0.002).

4. Discussion This study investigated the existence of electric and acoustic masking by psychoacoustic and electrophysiological measurements. Different combinations of maskers and probes were tested and described by the electric-acoustic frequency difference (EAFD). This study investigated masking in subjects with low residual hearing and deep electrode insertions. The results confirmed the existence of psychoacoustic threshold elevation of acoustic and electric probes under the influence of electric or acoustic maskers, respectively. In the electrophysiological masking experiment, responses to electric stimuli were significantly reduced due to the presence of acoustic maskers and vice versa.

Fig. 4. Difference potential (DIF) and sum potential (SUM) spectral amplitude for all subjects show as a function of the electric acoustic frequency difference (EAFD) in dB.

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Fig. 5. Potential waveforms (left top) and difference potential (DIF) waveforms (left bottom) for exemplary subject (ID 17) for acoustic only stimulation (black) and additional electric stimulation (colored). Analysis steps with spectral analysis (right top) and response reduction analysis for all measured combinations of stimulus frequencies and masker electrodes (right bottom).

4.1. Psychophysical masking experiment Electric and acoustic masking was assessed by a psychoacoustic experiment, comparable to the work of Krüger et al. (2017) and Lin et al. (2011), in subjects with deeper electrode insertion and more variable residual hearing. For 15 of the 17 subjects, the electric masking data is presented and discussed in Imsiecke et al. (2019). The two additional subjects showed very similar behavior in electric masking. Low EAFD, meaning close proximity of electric and acoustic stimulation, coincides with significant threshold elevation in both electric and acoustic masking in most subjects. The observed shape of electric threshold elevation, which differs from results reported by Krüger et al. (2017) and Lin et al. (2011), is replicated in the shape in the acoustic response amplitude of the DIF and SUM ECochG potentials as a function of the EAFD, which shows the strength of the response of the hair cells (mainly DIF potential) and the auditory nerve (mainly SUM potential) to acoustic stimulation. This might indicate that the assessment of place frequency according to Stakhovskaya et al. (2007) is offset by one octave from the actual

strongest response of hair cells and auditory nerve. A cause for this offset might be the shape of the elicited electric field, determined by contact shape, orientation, and placement as well as ground electrode placement. This might differ across electrode types, as the peak of masking was observed at zero octaves EAFD for a different electrode manufacturer (Krüger et al., 2017). The results of the acoustic masking reported in the present study are comparable to the results by Krüger et al. (2017). Electric threshold elevation is less strong than acoustic threshold elevation, the dependency on EAFD is less pronounced and the shape broader across subjects and EAFD. Krüger et al. (2017) hypothesized that this asymmetry might be caused by the upward spread of masking towards the basal region of the cochlea (Delgutte, 1990). In subjects with high frequency hearing loss, it would not be expected that residual hair cells are responsible for acoustic masking. It might be possible that more central mechanisms are involved in the upward spread of masking and hence in the observed acoustic masking of electric stimulation. The psychoacoustic experiment alone, however, cannot be used to investigate the origin of masking.

Fig. 6. Reduction of acoustic responses for different frequencies with additional electric stimulation on masker electrodes 1 (left), 2 (middle) and 3 (right) for individual subjects.

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Fig. 7. Example ECAP traces (left) and analysis (right) of ID 8 with electric-only (black) and combined electric-acoustic stimulation (colored) and the resulting change in ECAP amplitude shown for different stimulus electrodes or EAFD.

4.2. Electrophysiological masking experiment Electric and acoustic interaction on the level of the periphery was investigated by electrophysiological measurement of intracochlear potentials. Electric-acoustic interaction was hypothesized to stem from masking at the level of hair cells or auditory nerve, which was to be investigated for the two different masking modalities electric masking and acoustic masking individually. For the electric masking experiment, responses to acoustic and electric-acoustic stimulation were investigated. However, due to small amplitudes of the SUM potential, which contains mostly auditory nerve responses, and the absence of a visible CAP, the effect of electric masking on acoustically evoked neural responses could not be assessed in the present subject group with the used paradigm. Instead, the DIF response of the ECochG potential was analyzed. The effect of electric stimulation on the DIF potential,

which comprises mostly the hair cell response, was small but significant at the group level. Some subjects showed a reduction in acoustic response amplitude for EAFDs of around one octave. This peak of interaction has also been observed in psychoacoustic threshold elevation. It corresponds to the maximum amplitude of the electrophysiological response to acoustic stimulation as expressed across EAFD. This might indicate that the estimation of EAFD, i.e. the estimation of the place frequency for the electrode contacts, is offset for one octave for the electrode type used in these experiments, as it has not been observed in other electrodes (Krüger et al., 2017). As the number of significant peaks in the analysis of the DIF spectrum was small, a statistical analysis on the individual level did not show significant masking effects. Overall, the effect of electric stimulation on acoustic DIF response amplitude was small and not comparable to the threshold elevation observed in the

Fig. 8. Reduction of electric responses for different stimulus electrodes with additional acoustic stimulation for individual subjects.

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Fig. 9. Electric masking of acoustic response of DIF potential (left) and acoustic masking of electrically evoked compound action potentials (right).

psychoacoustic experiment. The difference and sum responses have been used to investigate interaction effects of electric-acoustic stimulation in EAS users by Koka and Litvak (2017). They showed a significant decrease in response amplitude of the DIF potential for various frequencies due to electric stimulation on different apical electrodes. The response reduction was highest for the most apical electrode with up to 8 dB, similar to the observed response reduction in this work. In animal experiments, electric masking has been shown to reduce activity at the stage of the auditory nerve (Stronks et al., 2010; Tillein et al., 2015) and in the inferior colliculus (Vollmer et al., 2010). However, no animal experiments reported on the effect of electric-acoustic interaction at the stage of hair cell responses, although an influence of electric stimulation on outer hair cells has long been documented (Brownell et al., 1985; Nuttall and Ren, 1995). It is possible that electric masking does not take place at the stage of hair cells, but at the auditory nerve, higher stages of the auditory pathway or at central stages, which could not be covered in the present study. However, the absence of similarly strong changes in acoustic responses as in the psychoacoustic masking setting, might be due to differences in the experimental setups. For the electrophysiological recordings, acoustic stimulation was delivered at upper comfortable level, to ensure the strongest possible electrophysiological responses. In contrast, threshold elevation is determined at far lower levels. It is possible that reduced masking is observed at higher levels of acoustic stimulation. This would correspond to findings in animals, where Stronks et al. (2010) reported stronger interaction effects for lower levels of acoustic stimulation and almost no change of acoustic responses at high acoustic levels. This limitation has been discussed by Koka and Litvak (2017), who also did not find corresponding effects in electrophysiological and psychoacoustic masking. For the acoustic masking experiment, responses of electric and acoustic-electric stimulation were investigated. McAnally et al. (1997) reported electrically evoked hair cell responses in animal experiments, thus the electrically evoked responses of the participants in this study were to be investigated in a similar manner. However, no electrophonic response could be observed in the traces or spectral analysis of the electric response. As the electric stimulation consisted of single pulses with an irregular and low repetition rate, the spectrum of the signal has the main

components in the very high frequencies. Subjects in the present study suffered from substantial to severe hearing loss in cochlear regions close to the implanted electrode array and at the spectral contents of the electric stimulation. Consequently, this lack of detectable hair cell response to electric stimulation is not unexpected. Other authors have also argued that electrophonic stimulation in hearing impaired humans is unlikely (Stronks et al., 2013). Acoustic masking was thus investigated by observing changes of neural responses between electric and acoustic-electric stimulation. A significant response reduction of ECAP amplitude was observed at the group level, which held for some subjects on an individual level. Acoustic masking was also observed for larger EAFD, where no or little surviving hair cells are assumed. The existence of ECAP reduction in these areas indicates that the effect of acoustic stimulation reduces the response to electric stimuli at the peripheral level of the auditory nerve. Studies in animals have shown a peripheral effect of acoustic maskers on electric stimulation, albeit in normal hearing animals (Nourski et al., 2005; Vollmer et al., 2010). In the present subject group, the interaction might be elicited by only a few remaining hair cells. Alternatively, central feedback mechanisms such as the lateral olivocochlear reflex might inhibit the response of the auditory nerve following acoustic stimulation and cause the reduction in ECAP (Groff and Liberman, 2003). As subjects with the lowest residual hearing showed the highest response reduction, this might indicate that higher acoustic presentation levels had an influence on ECAP reduction. The finding of ECAP response reduction through acoustic stimulation coincides with the observed psychoacoustic threshold elevation of electric stimuli with additional acoustic stimulation. However, the strength of masking seems to be smaller in the electrophysiological experiment, which indicates additional central masking effects. In animals, stronger ECAP reduction was observed for larger stimulus levels of electric stimulation (Nourski et al., 2005). The observed response reduction in the electrophysiological measurement could thus decrease towards the threshold levels used in the psychoacoustic experiments. Consequently, effects could be overestimated in the electrophysiological setup. No correlation between psychophysical behavioral threshold elevation and electrophysiological response reduction was found for neither electric nor acoustic masking. This indicates that the observed behavioral threshold elevation is not completely

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explained by peripheral masking found in this experiment. It might be explained by more central processes being involved in electricacoustic interaction. However, the paradigms for the psychophysical and the electrophysiological experiments were different, i.e. duration of test and masker stimuli and the level of the presented probe stimuli. While the psychophysical experiment is dependent on the estimation of a behavioral threshold, the electrophysiological experiment was conducted at above threshold levels, to obtain reliable responses from hair cells and auditory nerve. This difference in stimulation alone might explain the absence of a correlation between the results. The development of a setup that allows the parallel measurement of electrophysiological and psychoacoustic electric-acoustic interaction is feasible. Currently this is limited due to the technical possibilities of using the backward telemetry through the implanted electrode array. The electrophysiological measurement took similar time as the psychoacoustic experiment, but was less strenuous for subjects and would also be possible in subjects who have difficulties in fulfilling the task of the psychoacoustic experiment, such as children or elderly patients. Furthermore, it gives an objective estimation of peripheral processes that do not involve central processes and decision making. In the future, an online estimation of peripheral interaction during the surgical insertion of the electrode array might help to improve the positioning of the electrode array. The current method of partially inserting the electrode array based on anatomical data or ECochG responses (Lenarz et al., 2019; Campbell et al., 2016) could be adapted to stopping once interaction is observed. This could lead to a reduction in masking effects, which might influence speech perception (Imsiecke et al., 2019). 5. Conclusions The main findings of this study indicate the existence of electricacoustic interaction in subjects with deeper insertion angles and varying amounts of residual hearing. The asymmetry reported by Krüger et al. (2017) and Imsiecke et al. (2018) for psychoacoustic threshold changes was observed in both psychoacoustic and electrophysiological interaction experiments. Intracochlear potential responses towards electric, acoustic and electric-acoustic stimuli were recorded in MED-EL implants. These responses were analyzed for electric-acoustic interaction effects, to investigate at which stage along the auditory pathway the observed psychoacoustic masking results are found. The electrophysiological experiments showed interaction of electric and acoustic stimulation on the peripheral level, but of reduced strength in comparison to psychoacoustic threshold elevation. Changes in electrically elicited responses of the auditory nerve due to additional acoustic stimulation were for the first time reported in humans. Contrary to the hypothesis of earlier studies, which assumed that acoustic masking is a mostly central effect (Imsiecke et al., 2018; Krüger et al., 2017), these findings indicate that acoustic masking might originate from peripheral interaction. However, it remains unclear whether remaining hair cells cause the reduction of electrically evoked responses or whether ipsilateral central feedback loops might be involved. Electric masking was observed in the periphery at the stage of the hair cells, but to a smaller degree than expected from psychoacoustic experiments. Thus it cannot be confirmed whether additional, more central interaction is increasing the strength of electric masking effects. An optimization of the objective electrophysiological measurement paradigm in terms of measurement time and further automatization would be feasible to transfer the experimental setup into the clinical routine. Objectively estimating masking effects in an efficient manner could be used to assess the state of the auditory pathway and optimize speech processor fittings,

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especially in patients with limited communication abilities, for example children. CRediT authorship contribution statement Marina Imsiecke: Methodology, Software, Investigation, Formal analysis, Writing - original draft. Andreas Büchner: Supervision, Writing - review & editing. Thomas Lenarz: Resources, Supervision, Writing - review & editing. Waldo Nogueira: Conceptualization, Methodology, Software, Formal analysis, Funding acquisition, Writing - review & editing. Acknowledgements The authors would like to thank the subjects who have participated in the experiments and dedicated their time and effort to the experiments. This work was supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence EXC 1077/1, 2177/1 “Hearing4all”, the DFG project Number 396932747 and MED-EL Medical Electronics. References Aran, J., Charlet de Sauvage, R., 1976. Clinical value of cochlear microphonic recordings. Electrocochleography 55e65. Brownell, W.E., Bader, C.R., Bertrand, D., De Ribaupierre, Y., 1985. Evoked mechanical responses of isolated cochlear outer hair cells. Science 227, 194e196. €ver, T., Lesinski-Schiedat, A., Lenarz, T., Büchner, A., Schüssler, M., Battmer, R.D., Sto 2009. Impact of low-frequency hearing. Audiol. Neurotol. 14, 8e13. Campbell, L., Kaicer, A., Sly, D., Iseli, C., Wei, B., Briggs, R., O’Leary, S., 2016. Intraoperative real-time cochlear response telemetry predicts hearing preservation in cochlear implantation. Otol. Neurotol. 1 https://doi.org/10.1097/ MAO.0000000000000972. Dallos, P., Cheatham, M.A., Ferraro, J., 1974. Cochlear mechanics, nonlinearities, and cochlear potentials. J. Acoust. Soc. Am. 55, 597e605. Delgutte, B., 1990. Physiological mechanisms of psychophysical masking: observations from auditory-nerve fibers. J. Acoust. Soc. Am. 87, 791e809. Dorman, M.F., Gifford, R.H., Spahr, A.J., McKarns, S.A., 2008. The benefits of combining acoustic and electric stimulation for the recognition of speech, voice and melodies. Audiol. Neurotol. 13, 105e112. Forgues, M., Koehn, H.A., Dunnon, A.K., Pulver, S.H., Buchman, C.A., Adunka, O.F., Fitzpatrick, D.C., 2014. Distinguishing hair cell from neural potentials recorded at the round window. J. Neurophysiol. 111, 580e593.  Fraysse, B., Macías, A.R., Sterkers, O., Burdo, S., Ramsden, R., Deguine, O., Klenzner, T., Lenarz, T., Rodriguez, M.M., Von Wallenberg, E., et al., 2006. Residual hearing conservation and electroacoustic stimulation with the nucleus 24 contour advance cochlear implant. Otol. Neurotol. 27, 624e633. Gantz, B.J., Turner, C.W., 2003. Combining acoustic and electrical hearing. The Laryngoscope 113, 1726e1730. Gantz, B.J., Turner, C., Gfeller, K.E., Lowder, M.W., 2005. Preservation of hearing in cochlear implant surgery: advantages of combined electrical and acoustical speech processing. The Laryngoscope 115, 796e802. Gantz, B.J., Hansen, M.R., Turner, C.W., Oleson, J.J., Reiss, L.A., Parkinson, A.J., 2009. Hybrid 10 clinical trial. Audiol. Neurotol. 14, 32e38. Gfeller, K.E., Olszewski, C., Turner, C., Gantz, B., Oleson, J., 2006. Music perception with cochlear implants and residual hearing. Audiol. Neurotol. 11, 12e15. Groff, J.A., Liberman, M.C., 2003. Modulation of cochlear afferent response by the lateral olivocochlear system: activation via electrical stimulation of the inferior colliculus. J. Neurophysiol. 90, 3178e3200. Haumann, S., Imsiecke, M., Bauernfeind, G., Büchner, A., Helmstaedter, V., Lenarz, T., Salcher, R.B., 2019. Monitoring of the inner ear function during and after cochlear implant insertion using electrocochleography. Trends Hear. 23, 2331e2165. von Ilberg, C., Kiefer, J., Tillein, J., Pfenningdorff, T., Hartmann, R., Stürzebecher, E., Klinke, R., 1999. Electric-acoustic stimulation of the auditory system. ORL (OtoRhino-Laryngol.) (Basel) 61, 334e340. Imsiecke, M., Krüger, B., Büchner, A., Lenarz, T., Nogueira, W., 2018. Electric-acoustic forward masking in cochlear implant users with ipsilateral residual hearing. Hear. Res. 364, 25e37. Imsiecke, M., Krüger, B., Büchner, A., Lenarz, T., Nogueira, W., 2019. Interaction between electric and acoustic stimulation influences speech perception in EAS users. Ear Hear. https://doi.org/10.1097/AUD.0000000000000807. Koka, K., Litvak, L.M., 2017. Feasibility of using electrocochleography for objective estimation of electro-acoustic interactions in cochlear implant recipients with residual hearing. Front. Neurosci. 11. Krüger, B., Büchner, A., Lenarz, T., and Nogueira, W. (under review). Electric acoustic interaction measurements in cochlear implant users with ipsilateral residual hearing using electrocochleography. J. Acoust. Soc. Am.

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