Cochlear Implant Stimulation of a Hearing Ear Generates Separate Electrophonic and Electroneural Responses

Abstract

Electroacoustic stimulation in subjects with residual hearing is becoming more widely used in clinical practice. However, little is known about the properties of electrically induced responses in the hearing cochlea. In the present study, normal-hearing guinea pig cochleae underwent cochlear implantation through a cochleostomy without significant loss of hearing. Using recordings of unit activity in the midbrain, we were able to investigate the excitation patterns throughout the tonotopic field determined by acoustic stimulation. With the cochlear implant and the midbrain multielectrode arrays left in place, the ears were pharmacologically deafened and electrical stimulation was repeated in the deafened condition. The results demonstrate that, in addition to direct neuronal (electroneuronal) stimulation, in the hearing cochlea excitation of the hair cells occurs ("electrophonic responses") at the cochlear site corresponding to the dominant temporal frequency components of the electrical stimulus, provided these are < 12 kHz. The slope of the rate-level functions of the neurons in the deafened condition was steeper and the firing rate was higher than in the hearing condition at those sites that were activated in the two conditions. Finally, in a monopolar stimulation configuration, the differences between hearing status conditions were smaller than in the narrower (bipolar) configurations.

Significance statement: Stimulation with cochlear implants and hearing aids is becoming more widely clinically used in subjects with residual hearing. The neurophysiological characteristics underlying electroacoustic stimulation and the mechanism of its benefit remain unclear. The present study directly demonstrates that cochlear implantation does not interfere with the normal mechanical and physiological function of the cochlea. For the first time, it double-dissociates the electrical responses of hair cells (electrophonic responses) from responses of the auditory nerve fibers (electroneural responses), with separate excited cochlear locations in the same animals. We describe the condition in which these two responses spatially overlap. Finally, the study implicates that using the clinical characteristics of stimulation makes electrophonic responses unlikely in implanted subjects.

Keywords: cochlear implants; electroacoustic stimulation; electroneural stimulation; electrophony.

Figure 1.

Experimental setup. A, Recording electrodes and cochleostomy. B, Photograph of the cochlear implant. The device was inserted into the cochleostomy up to the black reference point. C, Acoustic receptive field indicating typical response in the inferior colliculus. Characteristic frequency was defined as the frequency with the lowest response threshold.

Figure 2.

Cochlear implantation in the guinea pig. A, Left, Round window niche and the view of the cochlea through the cochleostomy. Right, Position of the cochleostomy. B, Hearing thresholds defined as the lowest threshold determined at each tested frequency by the multielectrode array placed in the inferior colliculus. The data shown are means ± SD from all animals (n = 11). Red, Thresholds before implantation. Blue, Thresholds after implantation. Green, Thresholds after electrical stimulation (before pharmacological deafening).

Figure 3.

Effects of electrode position in the cochlea, biphasic pulse (100 μs/phase). A, Excitation profiles (spatial tuning curves) obtained for different narrow bipolar configurations in hearing (left) and deafened (right) cochlea in an example animal. White line shows the threshold in the hearing condition. Asterisk and arrow indicate sites with low thresholds. Changing the position of the active electrodes affected only the CF for the more basal low-threshold site (arrow); the more apical low-threshold site (asterisk) did not change. Deafening resulted in loss of the very sensitive low-CF responses (asterisk) at 4.6 kHz, but the basal response remained discernible and changed corresponding to the position of the active electrodes in the cochlea. B, Effects of stimulation configuration on thresholds in all 11 animals for low-CF sites (apical cochlea) in hearing (blue) and deafened (red) condition. The thresholds increased with basal shift of the active electrodes in both hearing and deafened conditions, but the effect was stronger for the hearing condition. C, Same data for high-CF sites (i.e., basal cochlea). For comparisons, the blue dashed curve represents the change in median threshold with position for the hearing condition in B, and the red line shows the same for the deaf condition in B. In the basal cochlea, the change of thresholds with cochlear position of the active electrode differs from the hearing condition in B, regardless of the hearing status. 40 dB_att correspond to 100 μA_pp. Two-tailed Wilcoxon-Mann–Whitney test, *∼5% significance level; **∼1% significance level; ***∼0.1% significance level.

Figure 4.

Effect of the spread of the electrical field, biphasic pulse (100 μs/phase). A, Example of excitation profiles for one hearing animal. The site's CF with lowest threshold (5.6 kHz) remained unaffected by the increase in spread of the electrical field. B, Data from the same animal after deafening. The low-threshold peak disappeared. C, Rate–level functions for the data in A. The site‘s CF is designated by color, starting with black (lowest CFs), blue (mid CFs) and green (high CFs). Sites with low CF show shallow rate–level functions. D, After deafening, shallow rate–level functions disappeared and thresholds increased. 40 dB_att correspond to 100 μA_pp.

Figure 5.

Population data on the effect of current spread, biphasic pulse (100 μs/phase). A, Threshold levels in all animals plotted separately for low CFs. Blue, Hearing condition. Red, Deafened condition. Increasing current spread decreases response thresholds in the deafened condition, but not in the hearing condition. B, Same data as in A, but for high CFs. Here, both the hearing and the deafened condition show a decrease in thresholds with increasing current spread. Two-tailed Wilcoxon-Mann–Whitney test, *∼5% significance level; **∼1% significance level; ***∼0.1% significance level. C–H, Rate–level functions pooled from all animals in hearing (blue) and deafened (red) condition, arranged with dB above hearing threshold. Gray bar above abscissa designates significant difference between hearing and deaf condition at the given current level (two-tailed Wilcoxon-Mann–Whitney test, α = 5%). C, E, G, Sites with low CF. Here, in the hearing condition the rate–level functions are less steep and the maximum firing rates lower than in the deafened condition. D, F, H, Sites with high CF. For these, the rate–level functions are more similar between deafened and hearing conditions, particularly for the broader configurations. However, the absolute firing rate is higher in deafened conditions. In general, the wider the configuration, the smaller the differences in shape of the rate–level functions. 40 dB_att correspond to 100 μA_pp.

Figure 6.

Effects of deafening on thresholds, biphasic pulse (100 μs/phase). A, Individual recording for narrow bipolar (1/2) configuration. In this example, lowest threshold is also observed for the hearing condition near 5 kHz. After deafening, the lowest threshold is at the site with previous CF between 9 and 10 kHz. B, Data from recordings where pairwise comparisons could be performed (details in the text). The range of thresholds was consistently higher for the hearing condition and largest for bipolar configuration (marked by the lines at the border of the panel). Data spread above the diagonal. C, The part of the data for sites with high CFs. Here, data points are clustered around the diagonal, indicating that deafening did not systematically change the thresholds and the loss in thresholds is predominantly due to the sites with low CFs. D, All data pooled from 11 animals for narrow bipolar configuration. Deafening leads to loss of thresholds both in the apical and basal cochlea. E, For broad bipolar configuration, the loss of thresholds is observed only in the apical cochlea. F, For monopolar configuration, loss of threshold with deafening is observed only in apical cochlea. 40 dB_att correspond to 100 μA_pp. Two-tailed Wilcoxon-Mann–Whitney test, *∼5% significance level; **∼1% significance level; ***∼0.1% significance level.

Figure 7.

Excitation profiles in a hearing cochlea stimulated with sinusoidal electrical stimulus of varying frequencies. A, Stimulation at 1 kHz resulted in one peak of activity with lowest threshold at the site with CF of 9.5 kHz, likely corresponding to the position of the active electrodes 1/2. Lowest CF observed in this experiment was 2 kHz. B, With stimulation at 2 kHz, an additional peak at the site with CF 2 kHz was observed, with the peak at 9.5 kHz unchanged apart from a threshold increase of 4 dB. The threshold of the 2 kHz peak was lower than the threshold for the site where CF = 9.5 kHz. C, At 3 kHz stimulation, the apical peak moved to the site with a CF of 2.4 kHz. D, With 4 kHz stimulation, the apical peak moved to 3.4 kHz, with a further increase in threshold of the peak at 9.5 kHz. E, At 6 kHz stimulation, the peaks merged and a substantial decrease in threshold was observed, with the best threshold at the site where CF = 6.7 kHz. F, At 8 kHz stimulation, the threshold dropped further, the lowest threshold being observed at the site where CF = 8 kHz. G, At 10 kHz, the peak moved to the site with 9.5 kHz CF, but the threshold increased substantially. H, At 12 kHz, one peak in the excitation profile was still observed, this time at the site where CF = 11 kHz. I, J, If stimulation frequency increased further, only the peak at 9.5 kHz was observed. 40 dB_att correspond to 100 μA_pp.