ABSTRACT
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 and
temporal bone histology suggest that peripheral pathology 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 neural encoding of sound.
The presence of specific cochlear pathologies and their relative contribution to perception, however, 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 anatomy and speech-in-noise perception when there are varying degrees of OHC and
non-OHC dysfunctions. This proposal tests our central hypothesis that identifying subtypes of SNHL from
integration of biomarkers sensitive to both OHC and non-OHC pathologies significantly improves prediction of
suprathreshold hearing over the audiogram alone. Using a cross-species approach, three synergistic specific
aims test our hypothesis. First, we assess the differences in biomarker profiles of two chinchilla models of distinct
SNHL subtypes, OHC-only hearing loss and complex SNHL (e.g., a combination of OHC, IHC, and AN
dysfunction), to measure the effect of non-OHC pathologies when they co-occur with OHC dysfunction. 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 histology from chinchillas with known exposures. Whether our hypotheses are supported or
refuted, this cross-species dataset will advance our understanding of the factors important for everyday
communication and establish a quantitative framework for developing more detailed diagnostic profiles. Greater
diagnostic precision that recognizes the multifactorial physiological underpinnings of SNHL will support
personalization of hearing healthcare and treatment, especially pharmaceutical interventions for hearing loss.
Additionally, the quantitative, cross-species, and professional training received through completion of these aims
complements my clinical training in audiology and will be foundational to my career as a translational auditory
neuroscientist.