Effects of age on electrophysiological measures of cochlear synaptopathy in humans

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 (WI(H)/WI(L)), and the difference between frequency following response (FFR) levels to shallow and deep amplitude modulated tones (FFR(S)-FFR(D)), 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 WI(H)/WI(L) and FFR(S)-FFR(D) 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). WI(H)/WI(L) in the presence of the HP noise did not decrease as a function of age. However, in the absence of HP noise, WI(H)/WI(L) showed credible age-related decreases even after partialing out the effects of audiometric threshold shifts. No credible age-related decreases of FFR(S)-FFR(D) 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.