PP309 - Evaluation of Auditory Evoked Potential Biomarkers of Cochlear Synaptopathy in Listeners with Self-Reported Hearing Difficulties

Abstract:
There is no standard diagnostic test for cochlear synaptopathy (CS), which affects auditory-nerve synapses and is linked to ageing, noise exposure, and ototoxicity. This study evaluates the usability of novel auditory-evoked-potential measures of CS in predicting overt or self-perceived hearing difficulties, age-related hearing loss, and speech recognition (N=120). RAM-based envelope-following responses were significantly smaller in subjects with self-reported hearing difficulties and correlated with the HHIE-s score. They were negatively correlated with age, indicating reduced temporal coding ability. We observed better sensitivity compared to the ABR wave-I amplitude, supporting their future use in clinical practice.

Summary:
Introduction
There is no standard diagnostic test for cochlear synaptopathy (CS), even though this pathology affects the auditory nerve synapses and is associated with ageing, noise exposure and ototoxicity. CS is expected to affect a large part of the population, which motivates the need for more studies on potential CS biomarkers and their relation to hearing difficulties. This study contributes to this effort by evaluating the overall usability and potential of several EFR markers in comparison to ABR wave-I characteristics. We also investigate the power of these EFR markers in predicting overt or self-perceived hearing difficulties, age-related hearing loss and speech recognition in noise.

Methods
We recruited subjects across three groups: a control group (N=60, ages 18-77) with normal audiograms and without self-reported hearing difficulties, a test group with self-reported hearing difficulties who had a HHIE-s questionnaire score above 4 and normal (N=60, ages 18-77) or impaired audiograms (N=70, ages 18 - 87). We selected 10 subjects per age-decade to ensure a normal distribution of age across the cohort. Subjects underwent ABR and EFR testing using a medical device under clinical investigation (NCT06114680 – clinicaltrials.gov) along with standard and extended-high-frequency audiometry and a Matrix sentence test in stationary noise. The EFR conditions included a 110-Hz harmonic tone complex and rectangularly-amplitude-modulated (RAM) pure tones at 2, 4 and 6 kHz. Their modulation frequency was 110 Hz, and stimulus levels were 70 dB SPL for EFR, ABR as well as speech stimuli. The selectivity of the chosen EFR markers to CS were either validated through auditory model simulations or animal-research studies of CS. Statistical analysis included pair-wise comparison t-tests as well as correlation statistics and were performed in python.

Results
EFRs recorded at 70 dB SPL were significantly smaller for participants with self-reported hearing difficulties and correlated with the HHIE-s score. EFRs showed a significant negative correlation with age (strongest for the 6, 4 and 0.11 kHz conditions), indicative of temporal envelope coding declines as we grow older, irrespective of specific hearing complaints. In the control group, there was no relation between the EFR strength and the average audiometric thresholds nor SRTs, suggesting that individual differences in their overall stronger EFRs did not relate to hearing ability. A significant negative correlation between the EFR and audibility and the SRT was present, indicating that temporal coding strength predicted both these measures for listeners with self-reported hearing deficits. Overall, we saw a better sensitivity of the EFR markers compared to the ABR wave-I amplitude.

Conclusions
Supra-threshold EFRs to different carrier frequencies provided a robust marker of self-reported hearing difficulties and objective speech-in-noise performance in those listeners with a HHIE-s score above 4. Furthermore, it appears that a certain degree of temporal coding deficits is necessary before hearing difficulties become apparent. Provided the improved sensitivity and test-retest reliability of EFR-based markers compared to ABR-based markers, their potential integration into clinical practice looks promising.

Brief Summary of Clinical Takeaways:
The clinical takeaway for this session is that novel auditory-evoked potential markers of cochlear synaptopathy effectively predict self-reported hearing difficulties. These markers may serve as a future diagnostic tool to identify and diagnose individuals with hearing challenges despite having normal audiograms.

Assumptions
Attendees should have familiarity with the basic concepts underlying auditory evoked potentials for hearing screening.