Aging Effects on Cortical Responses to Tones and Speech in Adult Cochlear-Implant Users

Abstract

Age-related declines in auditory temporal processing contribute to speech understanding difficulties of older adults. These temporal processing deficits have been established primarily among acoustic-hearing listeners, but the peripheral and central contributions are difficult to separate. This study recorded cortical auditory evoked potentials from younger to middle-aged (< 65 years) and older (≥ 65 years) cochlear-implant (CI) listeners to assess age-related changes in temporal processing, where cochlear processing is bypassed in this population. Aging effects were compared to age-matched normal-hearing (NH) listeners. Advancing age was associated with prolonged P2 latencies in both CI and NH listeners in response to a 1000-Hz tone or a syllable /da/, and with prolonged N1 latencies in CI listeners in response to the syllable. Advancing age was associated with larger N1 amplitudes in NH listeners. These age-related changes in latency and amplitude were independent of stimulus presentation rate. Further, CI listeners exhibited prolonged N1 and P2 latencies and smaller P2 amplitudes than NH listeners. Thus, aging appears to degrade some aspects of auditory temporal processing when peripheral-cochlear contributions are largely removed, suggesting that changes beyond the cochlea may contribute to age-related temporal processing deficits.

Appendices

APPENDIX 1

Quantification of Test–Retest Reliability

The test–retest reliability was calculated as the maximal cross-correlation (lag range ± 5 sampling points) across 0 to 350 ms of the response waveforms between the two sessions, using the ccf function implemented in R version 3.6.2 (Team 2013). The time range (0 to 350 ms) encompasses the P1-N1-P2 complex. The correlation coefficients ranged from −1 to 1. The cross-correlation analysis was applied to response waveforms from each electrode for each condition in individual listeners. To improve data normality, the correlation coefficients were converted into Fisher’s Z scores, which were used for later analyses.

Statistical Analysis

A linear mixed-effects model implemented via the lme4 package (Bates et al. 2014) in R version 3.6.2 (Team, 2013) was used to fit the data for test–retest reliability. The model included the following fixed effects: age at testing, hearing status (NH and CI), stimulus type (tone or speech), and ISI (0.5, 1, 2, 3, or 4 s). Age was centered using the mean age of all CI and NH listeners and was treated as a continuous variable. Hearing status, stimulus type, and ISI were treated as categorical variables. In the model, the reference levels were CI, an ISI of 0.5 s, and tone. The initial random effects were set as (1 | stimulus type × ISI | subject) + (1 + stimulus type × ISI | electrode).

To reduce the risk of data overfitting, we systematically remove random and fixed effects that did not contribute significantly to the model (p > 0.05) using the step function in the lmerTest package (Kuznetsova et al. 2017). Results from the simplest, best-fitting model were reported in the “Results” section. We computed the significance values for fixed effects in the optimal model using the anova function in the lmerTest package (Kuznetsova et al. 2017). We conducted post hoc analysis for significant fixed effects, if necessary, with the emmeans (for categorical variables) and emtrends (for continuous variables) functions in the emmeans package (Lenth et al. 2018a). Multiple comparisons were corrected by the Bonferroni method.

Results

Figure 9a, b display grand-average waveforms for the four groups comparing the two test sessions. The response waveforms were highly consistent across sessions. The addition of the sex variable into the optimal model for test–retest reliability significantly improved model fit (p = 0.045), wherein CAEPs from male listeners exhibited lower test–retest reliability than female listeners [F(1, 40.0) = 6.080, p = 0.018].

Fig. 9

Grand average waveforms to 1000-Hz tone (a) and syllable /da/ (b) for sessions 1 (gray thick lines) and 2 (black thin lines) averaged across the eight frontocentral electrodes for YCI, OCI, YNH, and ONH listeners across five inter-stimulus intervals (0.5, 1, 2, 3, and 4 s). Significant hearing status by stimulus type interaction (c) and hearing status by interstimulus interval (ISI) interaction (d) on cross-correlation coefficient (CC coef.). The CC coef. quantified the similarity of waveforms (0 to 350 ms) from the two sessions, which indexed test–retest reliability. The violin plots show distributions of raw data. Horizontal lines inside the violin plots represent individual observations. The length of each of those horizontal lines represents the number of observations at a given CC coef. relative to the maximum number of observations across all CC coefs. The line plots show means ± 1 standard deviation. Data for CI listeners (all YCI and OCI) are displayed in orange/thin lines/diamonds; data for NH listeners (all YNH and ONH) are displayed in black/thick lines/squares. YCI: younger to middle-aged adult cochlear-implant users, OCI: older adult cochlear-implant users, YNH: younger to middle-aged adults with normal hearing, ONH: older adults with normal hearing. *p < 0.05; **p < 0.01; ***p < 0.001

Of our primary interest, the main effect of age is not significant [F(1, 40.8) = 0.801, p = 0.376]. But the age × hearing status × ISI interaction was significant [F(4, 40.6) = 3.405, p = 0.017]. In addition, the non-age-based main effects hearing status [F(1, 39.8) = 16.918, p < 0.001] and ISI [F(4, 40.1) = 42.978, p < 0.001] were significant. The non-age-based interactions hearing status × stimulus type [F(1, 38.9) = 9.700, p = 0.003] and hearing status × ISI [F(4, 40.1) = 4.145, p = 0.007] were significant. Finally, other interactions (age × hearing status or age × ISI) were not significant (both ps > 0.260).

To understand the age × hearing status × ISI interaction, we compared the age effects across hearing status and ISIs. The interaction was probably driven by that the estimated age effect at the ISI of 0.5 s in NH listeners was significantly smaller than 0 (95% confidence interval: [−0.023, 0.0037]; p = 0.038, however, p = 0.374 after multiple-comparison correction), wherein responses from older NH listeners might exhibit lower test–retest reliability at the ISI of 0.5 s. But the estimated age effects at any other ISIs in NH listeners and any ISIs in CI listeners were not significantly different from zero (95% confidence intervals: [−0.019, 0.019]; all ps > 0.210 before multiple-comparison correction).

To understand the hearing status × stimulus type interaction, we compared the effect of hearing status across stimulus type and vice versa. The comparisons are displayed in Fig. 9c. The effect of hearing status on test-rest reliability (i.e., lower reliability in CI vs. NH listeners) was driven by the speech stimulus (p < 0.001) but not by the tone stimulus (p = 0.241). The effect of stimulus type on test-rest reliability (i.e., lower reliability in response to speech vs. tone) was driven by CI listeners (p = 0.036) but not NH listeners (p = 0.425).

To understand the hearing status × ISI interaction, we compared the effect of hearing status across ISIs and the effect of ISI across hearing status. The comparisons are displayed in Fig. 9d. The effect of hearing status on test-rest reliability (i.e., lower reliability in CI vs. NH listeners) was driven by ISIs ≥ 2 s (all ps < 0.05) but not by ISIs < 2 s (both ps > 0.23). For responses from CI listeners, the test-test reliability was lower for ISIs of 0.5 and 1 s compared to ISIs of 3 and 4 s (all ps < 0.05). The test-test reliability was not significantly different across other ISI comparisons (all ps > 0.068). For responses from NH listeners, the test–retest reliability significantly improved as the ISI increased from 0.5 s up to 2 s (0.5 s < 1 s < 2 s = 3 s = 4 s; all ps < 0.05).

Discussion

The test–retest reliability of CAEPs was lower in CI than NH listeners, particularly in response to the speech stimulus (Fig. 9c) and at longer ISIs (≥ 2 s: Fig. 9d). Simply, this may reflect that when processing stimuli, CI devices generate artifacts and contaminate the cortical responses, which leads to a reduction in test–retest reliability of CAEPs in CI listeners. But this explanation may not fully account for the lower test–retest reliability of CAEPs in CI listeners, considering that the test–retest reliability difference between CI and NH listeners is ISI-specific (i.e., at ISIs ≥ 2 s: Fig. 9d) and CAEPs at those ISIs (Fig. 9a, b) tend to show relatively high SNRs. The lower test–retest reliability of CAEPs in CI listeners may relate to biological changes associated with hearing impairments in CI listeners. For instance, CI listeners have undergone pathological changes in the auditory system, e.g., changes in the functioning of auditory nerve fibers, which can negatively influence their responses to CI electrical stimulation (Sly et al. 2007). As a result, cortical responses from CI listeners may become less reliable.

Furthermore, the test–retest reliability of CAEPs in CI and NH listeners generally improved with slower stimulus presentation rate (i.e., longer ISIs) and seemed to asymptote at an ISI around 2 s (Fig. 9d). Hence, practically, an ISI close to this value (i.e., 2 s) is recommended in future CAEP studies with relatively long stimuli (~500 ms) to ensure relatively high test-test reliability while maintaining a reasonable amount of test time (e.g., Friesen and Tremblay 2006).

APPENDIX 2

Waveforms across the 32 electrodes before (red lines) and after (blue lines) the removal of CI-related artifacts at an example condition from an example CI listener. For this listener, the stimuli were presented via the right ear. Note that, due to the presence of CI-related artifacts, response amplitudes before artifact removal are generally much larger than those after artifact removal. To help visualize them in the same plots, the amplitudes were scaled into the range of −1 to 1 by dividing individual amplitudes by the maximal absolute amplitude. The scaling was conducted separately for responses before and after artifact removal.