Towards a differential diagnosis of cochlear synaptopathy and outer-hair-cell deficits in mixed sensorineural hearing loss pathologies

Abstract

Damage to the auditory periphery is more widespread than predicted by the gold-standard clinical audiogram. Noise exposure, ototoxicity and aging can destroy cochlear inner-hair-cell afferent synapses and result in a degraded subcortical representation of sound while leaving hearing thresh- olds unaffected. Damaged afferent synapses, i.e. cochlear synaptopathy, can be quantified using histology, but a differential diagnosis in living hu- mans is difficult: histology cannot be applied and existing auditory evoked potential (AEP) metrics for synaptopathy become insensitive when other sensorineural hearing impairments co-exist (e.g., outer-hair-cell damage associated with elevated hearing thresholds). To develop a non-invasive diagnostic method which quantifies synaptopathy in humans and animals with normal or elevated hearing thresholds, we employ a computational model approach in combination with human AEP and psychoacoustics. We propose the use of a sensorineural hearing loss (SNHL) map which comprises two relative AEP-based metrics to quantify the respective de- grees of synaptopathy and OHC damage and evaluate to which degree our predictions of AEP alterations can explain individual data-points in recorded SNHL maps from listeners with normal or elevated audiometric thresholds. We conclude that SNHL maps can offer a more precise diag- nostic tool than existing AEP methods for individual assessment of the synaptopathy and OHC-damage aspect of sensorineural hearing loss.

Enhancing the sensitivity of the envelope-following response for cochlear synaptopathy screening in humans: the role of stimulus envelope

“…This is important because a strong baseline EFR response will be more sensitive to changes induced by alterations in the ANF population. At the same time, we adopt an optimized analysis 140 method which extracts all the relevant envelope-following components from the raw EEG recordings (Vasilkov & Verhulst, 2019). Furthermore, we studied how OHC functionality affects the EFR generators to different stimulation paradigms to evaluate which EFR markers are differentially sensitive to synaptopathy, even when OHC damage is simultaneously present.…”

The Derived-Band Envelope Following Response and its Sensitivity to Sensorineural Hearing Deficits

“…Previous studies have shown a dependency of the scalp-recorded AEP magnitude to head size, sex and age (Trune et al, 1988; Mitchell et al, 1989; Makary et al, 2011) and possible coexisting aspects of CS and OHC damage (Parthasarathy and Kujawa, 2018; Vasilkov and Verhulst, 2019). Hence, the spread of data-points within different recorded test-groups and spectral bandwidths could be explained by subject-specific factors unrelated to hearing or hearing-related factors associated with the main factors for grouping: (i) self-reported hearing difficulties in noisy environments in the first experiment, (ii) age and (iii) elevated hearing thresholds in the second experiment.…”

“…Since OHC-damage and CS might both affect the EFR magnitude (Garrett and Verhulst, 2019; Vasilkov and Verhulst, 2019), we employed a computational model of the auditory periphery to simulate how different degrees of CS affected the EFR PtN magnitude, both in presence and absence of high-frequency sloping OHC-loss above 1 kHz (simulated high-frequency sloping audiograms in Fig. 3).…”

“…The metric hence needs to be complemented with another supra-threshold metric sensitive to OHC damage to allow a separation of both the CS and OHC aspect of sensorineural hearing deficit from the DBEFR recorded from listeners with impaired audiograms (e.g. Vasilkov and Verhulst, 2019).…”

“…Lastly, the scalp-recorded AEP is strongly influenced by stimulus characteristics and the corresponding spread of basilar-membrane (BM) excitation, which can confound a frequency-specific diagnosis of CS (Bharadwaj et al, 2014, 2015; Verhulst et al, 2018a; Encina-Llamas et al, 2019). To address these issues, several studies have proposed differential/relative AEP-based metrics: the EFR amplitude slope as a function of modulation depth (Bharadwaj et al, 2014, 2015), ABR wave-V latency changes in different levels of background noise (Mehraei et al, 2016), EFR magnitude differences to stimuli with different modulation depths (Bharadwaj et al, 2015; Guest et al, 2018), or the combined use of EFR signal-to-noise ratios (SNRs) with ABRs to segregate mixed hearing pathologies and normalize inter-individual variabilities (Vasilkov and Verhulst, 2019). Secondly, a number of techniques have been proposed to confine ABR generation to specific frequency bands: the use of simultaneous off-frequency masking paradigms, i.e.…”