Characterizing cochlear neural degeneration using frequency-following responses

Our communication in social settings relies on our ability to accurately capture the acoustic environment through our sense of hearing. Hearing loss affects this ability, with detrimental consequences for many aspects of social life. Clinical hearing loss is in its most common age-related form defined as a loss of sensitivity, but not all hearing difficulties are necessarily captured by traditional clinical audiological assessment of sensitivity. Recent evidence suggests that neural losses at the level of the inner ear, the cochlea, can be caused by aging and noise exposure without affecting threshold sensitivity. Specifically, it has been shown that the amount of functional auditory nerve fibers (ANF) in the cochlea declines progressively throughout life. Such neural loss is argued to precede the loss of sensory cells in the cochlea and may exist before hearing loss is detected in the hearing clinic. Yet, the consequence of ANF loss on our ability to communicate in everyday life is still debated and robust in-vivo diagnostic measures are missing.
The work presented investigates electrophysiological frequency-following responses (FFR) as a potential measure of cochlear neural degeneration. FFRs are neurophonic potentials that phase-lock to the periodicity of an acoustic stimulus and can be recorded using scalp electroencephalography (EEG). It has previously been shown that the FFR to pure tones below 1 kHz is reduced with advancing age, and it has been argued that this reduction arises from age-related deficits in the auditory brainstem where the FFR originates. In this thesis, we challenged this hypothesis, and investigated the low-frequency FFR as a correlate of peripheral ANF loss in humans.
In the first study, we confirmed previously reported age-related reductions of the FFR by using frequency sweeps and pure tones in older normal-hearing listeners. The experimental results were compared to computer simulations of auditory nerve (AN) activity to the same stimuli informed by human histopathology. The simulations suggested that age-related ANF loss across cochlear frequency reduces the phase-locked population AN response in a manner consistent with the observed FFR reductions. Simulations also indicated that loss of outer hair cells had no detrimental effect on the synchronized AN response. In a second study, we further explored the relation between FFRs and AN integrity in a large cohort of aging listeners. The FFR was here compared to the wave-I of the auditory brainstem response (ABR), which reflects synchronized AN activity evoked by click sounds. We found strong reductions on the ABR wave-I amplitude with increasing age, and the reductions were correlated with the FFR reductions. In the third study, we further compared the effect of age on brainstem FFRs with neurophonic potentials arising from the AN by using recording electrodes placed on the tympanic membrane. The electrocochleography recordings again suggested an age-related reduction of neurophonic responses to low-frequency tones at the level of the AN. In a fourth study, we investigated the causal effect of ANF loss on the FFR by examining the effect of noise-induced ANF loss on the FFR using an animal (chinchilla) model of temporary threshold shift. Results again suggested that ANF loss reduces the population neurophonic response of the AN, but the relation to central FFRs was inconclusive from the data.
Together, the work presented in this thesis supports a relationship between age-related ANF loss and the brainstem FFR to low-frequency pure tones. As a result, the FFR might constitute valuable potential tool for diagnosing cochlear neural degeneration in humans.