Age-Related Decline in Neural Phase-Locking to Envelope and Temporal Fine Structure Revealed by Frequency Following Responses: A Potential Signature of Cochlear Synaptopathy Impairing Speech Intelligibility

频率跟随反应揭示的与年龄相关的神经相位锁定对包络和时间精细结构的下降:耳蜗突触病变损害言语清晰度的潜在特征

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Abstract

PURPOSE: Assessing the contribution of cochlear synaptopathy (CS) to the variability in speech-in-noise intelligibility among individuals remains a challenge. While several studies have proposed biomarkers for CS based on neural phase-locking to the temporal envelope (ENV), fewer have investigated how CS affects the coding of temporal fine structure (TFS), despite its crucial role in speech-in-noise perception. In this study, we specifically examined whether TFS-based markers of CS could be derived from electrophysiological responses and psychophysical detection thresholds of spectral modulation (SM) in a complex tone, which serves as a parametric model of speech. METHODS: We employed an integrated approach, combining psychophysical testing with frequency-following response (FFR) measurements in three groups of participants: young normal-hearing (n = 15, 12 females, age 21 ± 1); older normal-hearing (n = 16, 11 females, age 47 ± 6); and older hearing-impaired (n = 14, 8 females, age 52 ± 6). We expanded on previous work by assessing phase-locking to both ENV, using a 4-kHz rectangular amplitude-modulated (RAM) tone, and TFS, using a low-frequency (< 1.5 kHz) SM complex tone. RESULTS: Overall, FFR results showed significant reductions in neural phase-locking to both ENV and TFS components with age and hearing loss. Specifically, the strength of TFS-related FFRs, particularly the component corresponding to the harmonic closest to the peak of the spectral envelope (~ 500 Hz), was negatively correlated with age, even after adjusting for audiometric thresholds. This TFS marker also correlated with ENV-related FFRs derived from the RAM tone, suggesting a shared decline in phase-locking capacity across low and high cochlear frequencies. Computational simulations of the auditory periphery indicated that the observed FFR strength reduction with age is consistent with approximately 50% loss of auditory nerve fibers, aligning with histopathological data. However, the TFS-based FFR marker did not account for variability in speech intelligibility observed in the same participants. Psychophysical measurements showed no age-related effects and were unrelated to the TFS-based FFR marker, highlighting the need for further psychophysical research to establish a behavioral counterpart. CONCLUSION: Altogether, our results demonstrate that FFRs to vowel-like stimuli can serve as a complementary electrophysiological marker for assessing neural coding fidelity to stimulus TFS. This approach could provide a valuable tool for better understanding the impact of CS on an important coding dimension for speech-in-noise perception.

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