Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age. Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.

Auditory brainstem responses (ABRs), and envelope and frequency following responses (EFRs and FFRs) are widely used to study aberrant auditory processing in conditions such as aging. We have previously reported age-related deficits in auditory processing for rapid amplitude modulation (AM) frequencies using EFRs recorded from a single channel. However sensitive testing of EFRs along a wide range of modulation frequencies is required to gain a more complete understanding of the auditory processing deficits. In this study, ABRs and EFRs were recorded simultaneously from two electrode configurations in young and old Fischer-344 rats, a common auditory aging model. Analysis shows that the two channels respond most sensitively to complementary AM frequencies. Channel 1, recorded from Fz to mastoid, responds better to faster AM frequencies in the 100–700 Hz range of frequencies, while Channel 2, recorded from the inter-aural line to the mastoid, responds better to slower AM frequencies in the 16–100 Hz range. Simultaneous recording of channels 1 and 2 using AM stimuli with varying sound levels and modulation depths show that age related deficits in temporal processing are not present at slower AM frequencies but only at more rapid ones, which would not have been apparent recording from either channel alone. Comparison of EFRs between unanesthetized and isoflurane anesthetized recordings in young animals, as well as comparison with previously published ABR waveforms, suggests that the generators of Channel 1 may emphasize more caudal brainstem structures while those of Channel 2 may emphasize more rostral auditory nuclei including the inferior colliculus and the forebrain, with the boundary of separation potentially along the cochlear nucleus/superior olivary complex. Simultaneous two channel recording of EFRs help to give a more complete understanding of the properties of auditory temporal processing over a wide range of modulation frequencies which is useful in understanding neural representations of sound stimuli in normal, developmental or pathological conditions

Hearing thresholds and wave amplitudes measured using auditory brainstem responses (ABRs) to brief sounds are the predominantly used clinical measures to objectively assess auditory function. However, frequency-following responses (FFRs) to tonal carriers and to the modulation envelope (envelope-following responses or EFRs) to longer and spectro-temporally modulated stimuli are rapidly gaining prominence as a measure of complex sound processing in the brainstem and midbrain. In spite of numerous studies reporting changes in hearing thresholds, ABR wave amplitudes, and the FFRs and EFRs under neurodegenerative conditions, including aging, the relationships between these metrics are not clearly understood. In this study, the relationships between ABR thresholds, ABR wave amplitudes, and EFRs are explored in a rodent model of aging. ABRs to broadband click stimuli and EFRs to sinusoidally amplitude-modulated noise carriers were measured in young (3-6 months) and aged (22-25 months) Fischer-344 rats. ABR thresholds and amplitudes of the different waves as well as phase-locking amplitudes of EFRs were calculated. Age-related differences were observed in all these measures, primarily as increases in ABR thresholds and decreases in ABR wave amplitudes and EFR phaselocking capacity. There were no observed correlations between the ABR thresholds and the ABR wave amplitudes. Significant correlations between the EFR amplitudes and ABR wave amplitudes were observed across a range of modulation frequencies in the young. However, no such significant correlations were found in the aged. The aged click ABR amplitudes were found to be lower than would be predicted using a linear regression model of the young, suggesting altered gain mechanisms in the relationship between ABRs and FFRs with age. These results suggest that ABR thresholds, ABR wave amplitudes, and EFRs measure complementary aspects of overlapping neurophysiological processes and the relationships between these measurements changes asymmetrically with age. Hence, measuring all three metrics provides a more complete assessment of auditory function, especially under pathological conditions like aging.

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