Abstract
Age-related cochlear synaptopathy (CS) has been shown to occur in rodents with minimal noise exposure, and has been hypothesized to play a crucial role in age-related hearing declines in humans. Because CS affects mainly low-spontaneous rate auditory nerve fibers, differential electrophysiological measures such as the ratio of the amplitude of wave I of the auditory brainstem response (ABR) at high to low click levels (WIH/WIL), and the difference between frequency following response (FFR) levels to shallow and deep amplitude modulated tones (FFRS-FFRD), have been proposed as CS markers. However, age-related audiometric threshold shifts, particularly prominent at high frequencies, may confound the interpretation of these measures in cross-sectional studies of age-related CS. To address this issue, we measured WIH/WIL and FFRS-FFRD using highpass masking (HP) noise to eliminate the contribution of high-frequency cochlear regions to the responses in a cross-sectional sample of 102 subjects (34 young, 34 middle-aged, 34 older). WIH/WIL in the presence of the HP noise did not decrease as a function of age. However, in the absence of HP noise, WIH/WIL showed credible age-related decreases even after partialing out the effects of audiometric threshold shifts. No credible age-related decreases of FFRS-FFRD were found. Overall, the results do not provide evidence of age-related CS in the low-frequency region where the responses were restricted by the HP noise, but are consistent with the presence of age-related CS in higher frequency regions.
Highlights
Hearing loss is one of the most common chronic conditions in older adults (Lin et al, 2011)
Not all of the predictors shown in the table were used in all models (e.g. PTA4–12 was only included for the auditory brainstem response (ABR) model in quiet in which high-frequency cochlear contributions were not noise masked), for details of the predictors used in each model see Section 2.10
For simplicity the correlations of the PTA1–2 variable used in the frequency following response (FFR) models have been omitted from the table because they were very similar to the correlations of the PTA0.5–2 variable
Summary
Hearing loss is one of the most common chronic conditions in older adults (Lin et al, 2011). CS has been widely documented in rodents as a result of acoustic trauma: Noise exposures titrated to cause only temporary threshold shifts, in the absence of permanent OHC damage, have been shown to result in a permanent loss of synapses between the IHCs and auditory nerve fibers (Kujawa and Liberman, 2009). This loss of afferent synapses is thought to affect mainly auditory nerve fibers with low and medium spontaneous firing rates (L/M-SR fibers) that are considered to be important for coding sounds at high levels. Indirect evidence comes from the observation that while CS does not affect neurophysiological responses at low stimulus levels, it leads to reductions of neurophysiological responses at supra-threshold stimulus levels, in particular of wave I of the auditory brainstem response (ABR), of the frequency following response (FFR) to high-frequency (∼1-kHz) amplitude modulation (Shaheen et al, 2015), and of the middle ear muscle reflex (Valero et al, 2016, 2018)
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