Individualized Profiles of Sensorineural Hearing Loss from Non-Invasive Biomarkers of Peripheral Pathology

<p dir="ltr">The audiogram is the cornerstone of clinical hearing assessment, but individual differences in speech perception, especially in noisy environments, cannot be explained by audibility alone. People with normal hearing thresholds often complain of difficulty understanding speech-in-noise, and listeners with sensorineural hearing loss (SNHL) show significant variability in speech perception, even when audibility is restored. Animal models of SNHL as well as temporal bone histology suggest that peripheral pathologies missed by the audiogram may explain some of this variance. Outer hair cell (OHC) dysfunction elevates hearing thresholds, but inner hair cell (IHC) and auditory nerve (AN) dysfunction may be hidden from the audiogram despite their impact on the neural encoding of sound. However, the presence of specific cochlear pathologies and their relative contribution to perception cannot be directly tested in humans. Instead, non-invasive biomarkers of pathology are used. Though diagnostics have been developed for identifying hidden pathologies in people with normal hearing, an individual metric is unlikely to be enough when SNHL results from a combination of peripheral dysfunctions. To address this gap, we use a battery of non-invasive diagnostic tools to determine a biomarker profile for individual subjects and assess its relationship to cochlear histopathology and speech-in-noise perception when there are varying types and degrees of OHC and non-OHC dysfunctions. This cross-species dataset tests our central hypothesis that identifying subtypes of SNHL from integration of biomarkers sensitive to both OHC and non-OHC pathologies significantly improves detection of specific cochlear dysfunctions and prediction of suprathreshold hearing over the audiogram alone. First, we assess the sensitivity of individual assays to four pre-clinical chinchilla models of SNHL. Second, we measure physiological biomarker profiles in humans with SNHL and test whether they better predict speech understanding than the audiogram. Third, using our coordinated physiological test battery as a link between species, we make predictions about the underlying cochlear pathology distributions in humans with complex SNHL based on our findings in chinchillas with known exposures. This dissertation advances our understanding of the factors important for everyday communication and establishes a quantitative framework for the development of more detailed diagnostic profiles. Greater diagnostic precision that recognizes the multifactorial physiological underpinnings of SNHL supports personalization of hearing healthcare and treatment.</p>