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Research ArticleResearch Article: New Research, Disorders of the Nervous System

Deciphering Compromised Speech-in-Noise Intelligibility in Older Listeners: The Role of Cochlear Synaptopathy

Markus Garrett, Viacheslav Vasilkov, Manfred Mauermann, Pauline Devolder, John L. Wilson, Leslie Gonzales, Kenneth S. Henry and Sarah Verhulst
eNeuro 9 January 2025, 12 (2) ENEURO.0182-24.2024; https://doi.org/10.1523/ENEURO.0182-24.2024
Markus Garrett
1Medizinische Physik and Cluster of Excellence “Hearing4all”, Department of Medical Physics and Acoustics, Carl von Ossietzky University of Oldenburg, Oldenburg 26129, Germany
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Viacheslav Vasilkov
2Hearing Technology @ WAVES, Department of Information Technology, Ghent University, Zwijnaarde 9052, Belgium
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Manfred Mauermann
1Medizinische Physik and Cluster of Excellence “Hearing4all”, Department of Medical Physics and Acoustics, Carl von Ossietzky University of Oldenburg, Oldenburg 26129, Germany
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Pauline Devolder
2Hearing Technology @ WAVES, Department of Information Technology, Ghent University, Zwijnaarde 9052, Belgium
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John L. Wilson
3Department of Otolaryngology, University of Rochester, Rochester, New York 14642
4Department of Neuroscience, University of Rochester, Rochester, New York 14642
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Leslie Gonzales
4Department of Neuroscience, University of Rochester, Rochester, New York 14642
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Kenneth S. Henry
3Department of Otolaryngology, University of Rochester, Rochester, New York 14642
4Department of Neuroscience, University of Rochester, Rochester, New York 14642
5Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627
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Sarah Verhulst
2Hearing Technology @ WAVES, Department of Information Technology, Ghent University, Zwijnaarde 9052, Belgium
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Figures

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  • Figure 1.
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    Figure 1.

    Pure-tone hearing thresholds (in dB HL) at frequencies between 0.125–8 kHz. Groups were based on audiogram and DPOAE thresholds and age. yNHcontrol: young normal hearing control group (blue), oNH: old normal hearing (orange), oHI: old hearing impaired (red). Thick traces represent the group mean and thin traces represent individual audiogram profiles. Note that two subjects from the recruited NH group did not meet the THDP threshold criterion for normal hearing to be included in the control group. The audiograms of these NH subjects were indicated with thin black traces. The 20 dB HL hearing threshold (THA), which was used to separate listeners into oNH or oHI subgroups, was indicated by a gray dashed curve.

  • Figure 2.
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    Figure 2.

    Comparison between human (panel A) and Budgerigar (panel B) EFR recordings and analysis procedures for single subjects. For each species, the top row corresponds to the SAM stimulus and the bottom row to the RAM stimulus. The modulation frequencies and depths were 120 Hz (95% md) and 100 Hz (100% md) for humans and budgerigars, respectively. Carrier frequencies were 4 kHz (68 dB SPL RAM, 70 dB SPL SAM) and 2.83 kHz (75 dB SPL), respectively. Time-domain responses (right panels) show the filtered EEG recording along with the reconstructed time-domain waveform that was based on five frequency components (h0 − h4) and their respective phases. The EFR amplitude (or, EFR marker) was extracted from the reconstructed time-domain EFR following Equation 3, which was based on an iFFT of the noise-floor-corrected mean EFR magnitude (left panels). The budgerigar recordings (panel B) are shown for the same animal before or after kainic-acid (KA) administration. Post-KA spectral peaks and reconstructed EFRs were smaller than pre-KA EFRs.

  • Figure 3.
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    Figure 3.

    A, EFR amplitudes from three Budgerigars (B132, B120, B125) before or several weeks after administration of kainic acid (KA). B, Representative cross sections of the Budgerigar cochlea from a control ear (left) and from an ear exposed to 1-mM KA solution (12 weeks post exposure; right). Sections are stained for DAPI and Myosin 7A, and are from the location 50–60% of the distance from the apex to the base (≈2-kHz cochlear frequency; see Wang et al., 2023). KA exposure causes marked reduction of auditory-nerve (AN) peripheral axons and cell bodies in the AN ganglion, without impacting the hair-cell epithelium. C, Boxplots and individual data points of the Budgerigar SAM and RAM EFR amplitudes before or after KA-administration. Connected lines correspond to data from the same animal. To account for both paired and independent data in the Budgerigar sample, we performed a partially overlapping samples t-test and reported significance as: *p < .05, **p < .01 and ***p < .001. D, Boxplots and individual data points of human SAM and RAM EFR amplitudes. Data are show for the different test groups based on age and THAs: yNHcontrol, oNH and oHI, as well as for the pooled OLD group (oNH+oHI). Independent samples t-tests were performed between all conditions for the SAM and RAM conditions separately, and significance was reported as: *p < .05, **p < .01 and ***p < .001 after applying a Bonferroni correction of 6.

  • Figure 4.
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    Figure 4.

    Speech reception thresholds (SRT) for the OLSA matrix sentence test presented in quiet A, and in speech-shaped noise B, for three conditions: original (BB), low-pass-filtered speech and noise material (fc = 1.5 kHz; LP), high-pass filtered speech and noise material (fc = 1.65 kHz; HP). SRTs are grouped by the selection groups (yNHcontrol, oNH, oHI), as well as pooled across oNH and oHI subjects into an older group (OLD). Independent t-tests were computed between the groups in each condition for the quiet and noise conditions separately, and significant differences were indicated on the figure. The p-values were Bonferroni corrected before their significance was reported as (*) p < .05, (**) p < .01 and (***) p < .001. A Bonferroni correction of 18 was applied for the yNHcontrol, oNH and oHI group comparisons, and of 6 for the yNHcontrol and OLD comparisons.

  • Figure 5.
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    Figure 5.

    Regression plots between SRTSiQ and the EFR amplitudes for RAM (top) and SAM stimuli (bottom). Analyses are performed for the BB (A,D), LP (B,E) and HP filtered conditions (C,F). Subjects belonging to the yNHcontrol, oNH, oHI groups are color-coded and the two yNH subjects who did not meet the THDP criterion to be included in the yNHcontrol group are marked with crosses. Correlation statistics (ρ or r) are indicated on the each panel and are performed across the entire cohort (ALL), or subgroups of OLD (oNH+oHI) or NH (yNH+oNH) subjects.

  • Figure 6.
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    Figure 6.

    Regression plots between SRTSiN and the EFR amplitudes for RAM (top) and SAM stimuli (bottom). Analyses are performed for the BB (A,D), LP (B,E) and HP filtered conditions (C,F). Subjects belonging to the yNHcontrol, oNH, oHI groups are color-coded and the two yNH subjects who did not meet the THDP criterion to be included in the yNHcontrol group are marked with crosses. Correlation statistics (ρ or r) are indicated on each panel and are performed across the entire cohort (ALL), or subgroups of OLD (oNH+oHI) or NH (yNH+oNH) subjects.

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    Figure 7.

    Residuals of a linear regression model between the SRT and THA for the different SRT conditions: BB, LP, HP. The applied THA for each of the conditions was adjusted to the frequency range of the speech material. The THA correction applied refers to the mean THA across the 0.125–8 kHz (BB), 0.125–1.5 kHz (LP), and 1.5–8 kHz (HP) intervals, respectively. Indicated correlation statistics refer to the ρ or r calculated between the THA-corrected SRTs and the RAM EFR, and were either calculated across the entire cohort (ALL) or subgroups of NH (yNH+oNH) or OLD (oNH + oHI) subjects.

  • Figure 8.
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    Figure 8.

    Reanalysis of the Encina-Llamas et al. (2017) dataset reporting EFR magnitudes to a 98-Hz SAM tone of 4011 Hz. dB values were transformed into μV using a 10**(dB/20) transformation with 1 μV as the reference. Data from 13 NH (24 ± 3.2 y/o) and 7 HI (56.2 ± 12.7 y/o) listeners are shown. Only EFR amplitudes that were significantly above the noise floor are shown, and a linear fit was made across data-points above the compression knee-point of 60 dB SPL. The NH cohort had audiogram thresholds below 15 dB HL for frequencies below 8 kHz and the HI cohort had dB HL thresholds <=20 for frequencies below 4 kHz and between 20 and 45 dB HL for frequencies up to 8 kHz.

Tables

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    Table 1.

    Relationship between the EFR marker SRT

    SRTBBSRTLPSRTHP
    SiQp < .001p = .003p < .001
    ρ = −0.55ρ = −0.44ρ = −0.70
    SiNp < .001p = .024p < .001
    ρ = −0.61ρ = −0.34ρ = −0.73
    • Correlation statistics between the RAM EFR marker and SRTSiQ and SRTSiN across the entire cohort (n = 44) for different filtering conditions (BB, LP, HP).

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    Table 2.

    Linear regression analysis between SRT and variables RAM EFR, age and threshold

    SRTSiN,HP = f(β1X1, β2X2)Adj. R2 F (df1,df2)p
    RAM EFR0.45F(1, 42) = 36.42p < .001
    THA,4 kHz0.51F(1, 42) = 47.35<.001
    THDP,4 kHz0.36F(1, 42) = 25.84<.001
    Age0.58F(1, 42) = 59.87<.001
    RAM EFR + THA,4 kHz0.60F(2, 41) = 33.01<.001
    RAM EFR + THDP,4 kHz0.51F(2, 41) = 23.39<.001
    RAM EFR * THA,4 kHz0.63F(3, 40) = 23.48<.001X1:X2 n.s.
    RAM EFR * THDP,4 kHz0.50F(3, 40) = 15.42<.001X1:X2 n.s
    SRTSiQ,HP = f(β1X1, β2X2)Adj. R2 F (df1,df2)p
    RAM EFR0.33F(1, 42) = 22.33p < .001
    THA,4 kHz0.76F(1, 42) = 134.1<.001
    THDP,4 kHz0.51F(1, 42) = 46.21<.001
    Age0.54F(1, 42) = 52.41<.001
    RAM EFR + THA,4 kHz0.75F(2, 41) = 66.95<.001
    RAM EFR + THDP,4 kHz0.54F(2, 41) = 26.3<.001
    RAM EFR * THA,4 kHz0.77F(3, 40) = 48.66<.001X1:X2 n.s.
    RAM EFR * THDP,4 kHz0.53F(3, 40) = 17.44<.001X1:X2 n.s
    • Linear regression models for SRTHP in noise (SiN) and quiet (SiQ) conducted for the entire cohort.

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    Table 3.

    Linear regresssion and commonality analysis for SRTHP

    lm=β1X1+β2X2+ϵ Adj. R2 F (df1,df2)pparametersuniquecommon
    SRTSiN-HP0.60F(2, 41) = 33.01<.05β1 = −13.11**14.1%61.2%
    X1 = RAM EFRβ2 = 0.1***24.7%
    X2 = THA,4 kHz ϵ = 2.87*
    SRTSiN-HP,NH0.64F(2, 27) = 26.86<.05β1 = −13.20***34.7%24.3%
    β2 = 0.22***41.0%
    ϵ = 2.09*
    SRTSiN-HP,OLD0.23F(2, 26) = 5.3=0.01β1 = −5.094.2%42.3%
    β2 = 0.07*53.5%
    ϵ = 2.90*
    SRTSiQ-HP0.75F(2, 41) = 66.95<.05β1 = −10.260.5%44.8%
    β2 = 0.6***54.7%
    ϵ = 37.78***
    SRTSiQ-HP,NH0.61F(2, 27) = 24.64<.05β1 = −10.72.2%12.71%
    β2 = 1.02***85.0%
    ϵ = 35.0***
    SRTSiQ-HP,OLD0.6F(2, 26) = 22.2<.01β1 = 17.161.4%15.6%
    β2 = 0.53***83%
    ϵ = 37.14***
    • Linear regression models for SRTHP in noise (SiN) or in quiet (SiQ). Regressions were performed on the entire cohort as well as in subgroups of normal-hearing (NH), or older (OLD) subjects. All models had a normal distribution of residuals, and a colinearity (vif) factor below 1.61 (i.e., independent parameters). Significance codes: ***p ≤ .001, **p ≤ .01, *p ≤ .05.

    • View popup
    Table 4.

    Statistics test examining whether SAM EFR amplitudes are different across subjects with or without impaired audiograms for stimulation at different presentation levels [dB SPL]

    SAM EFR level
    [dB SPL ]t(d.f.)p
    60t(12) = 1.49p = .16
    65t(13) = 1.20p = .29
    70t(14) = 1.61p = .13
    75t(15) = 0.67p = .50
    80t(17) = 1.24p = .23
    • Results from independent t-tests conducted on the Encina-Llamas et al. (2017) dataset reporting EFR magnitudes to a 98-Hz SAM tone of 4,011 Hz and shown in Figure 8. All t-tests showed that the NH EFR amplitudes were not significantly different from the HI EFR amplitudes when presented at the same stimulus level. Only EFR amplitudes that were significantly above the noise floor were included for each stimulus level condition listed in the table.

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Deciphering Compromised Speech-in-Noise Intelligibility in Older Listeners: The Role of Cochlear Synaptopathy
Markus Garrett, Viacheslav Vasilkov, Manfred Mauermann, Pauline Devolder, John L. Wilson, Leslie Gonzales, Kenneth S. Henry, Sarah Verhulst
eNeuro 9 January 2025, 12 (2) ENEURO.0182-24.2024; DOI: 10.1523/ENEURO.0182-24.2024

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Deciphering Compromised Speech-in-Noise Intelligibility in Older Listeners: The Role of Cochlear Synaptopathy
Markus Garrett, Viacheslav Vasilkov, Manfred Mauermann, Pauline Devolder, John L. Wilson, Leslie Gonzales, Kenneth S. Henry, Sarah Verhulst
eNeuro 9 January 2025, 12 (2) ENEURO.0182-24.2024; DOI: 10.1523/ENEURO.0182-24.2024
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Keywords

  • cochlear synaptopathy
  • envelope-following response
  • outer hair cell damage
  • reception threshold
  • sensorineural hearing loss
  • speech-in-noise
  • speech
  • speech intelligibility

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