Characterizing cochlear hearing impairment using advanced electrophysiological methods

One of the impressive and not fully understood abilities of the healthy auditory system is the property of enabling successful communication in highly complex acoustical environments with high levels of background noise. In order to do so, the complex biological machinery in the auditory periphery must function with precision to transform the sound into neural activity that the brain can interpret.

Dysfunction or loss of the cells that underlay such transformation leads to a disruption or degradation of the sound encoding. Restoration strategies through the use of prosthetic devices (i.e. hearing aids) have been proposed to compensate for those deficits, but these are not always entirely successful, and do not target the specific physiological deficit leading to the hearing loss or dysfunction.

Thus, aided, hearing-impaired (HI) listeners commonly do not perform as proficiently as normal-hearing (NH) listeners, which can result in frustrating experiences. An accurate assessment of the precise deficits of the auditory system may allow for the development of more precise and individualized compensation strategies.

The gold-standard metric today to evaluate the peripheral auditory system is pure-tone threshold audiometry. This is still the case even with direct physiological evidence from animal models that a substantial loss or dysfunction of sensory inner hair cells (IHC) and/or auditory nerve (AN) fiber synapses is not strongly related to pure-tone threshold.

On the other hand, loss or dysfunction of actuator outer hair cells (OHC) have been clearly related to the elevation of hearing thresholds. This might explain why some people with normal hearing sensitivity report difficulties in speech understanding and music perception in complex acoustical scenarios.

In order to examine the potential effect of such "hidden" pathologies on supra-threshold perception, this thesis describes the investigation of supra-threshold processing by means of electrophysiological methods. More precisely, envelope following responses (EFR) recorded as a function of stimulus level (level-growth) were proposed as a method to estimate compression in the peripheral auditory system, and to investigate the potential effect of damage of AN fibers synapses.

Firstly, EFR level-growth functions using multiple carrier frequency stimuli were recorded in NH and mild-HI listeners to estimate peripheral compression. The results showed that EFRs provide similar estimates of auditory peripheral compression to those reported in the previous literature. However, the place-specificity of the compression estimates may be compromised due to contributions from off-frequency (i.e. away from the characteristic place of the stimulus) neural populations to the EFR.

Secondly, EFR level-growth functions were measured for strongly and shallowly modulated tones in NH threshold and mild-HI listeners to study the postulated presence of loss of AN fiber synapses (i.e. cochlear synaptopathy). The results revealed different patterns within the homogeneous group of young-NH threshold listeners and in the mild-HI listeners.

Similar patterns were observed in noise-exposed mice in contrast to an unexposed control group. A well-established phenomenological computational model of the AN was used to investigate the potential relation between the recorded EFR level-growth functions in humans and mice and the postulated presence cochlear synaptopathy.

The model simulations suggested that the contribution of off-frequency neural activity dominate the response of the AN to modulated tones at medium-to-high stimulus levels, and potentially also the recorded EFR. In the light of the results described in this thesis it was suggested that the combination of non-invasive electrophysiology in humans and non-human mammals and computational modeling may be a promising approach to study and better characterize supra-threshold processing in the auditory system.