The proposed work will identify the origin of objective auditory responses that are widely used to screen for hearing loss in well-baby nurseries. Additionally, we will use a new response measure to gain fresh insight into the hearing loss associated with Mnire's disease. Understanding the origins of auditory responses in normal and diseased ears is critically needed for accurate interpretation of clinical tests and for developing new therapies.
Acoustic and electrical measurements from normal and diseased ears have many uses but their origins are not fully understood. This work proposes to identify the origin of several objective auditory responses in ears with and without hearing loss. Transient-evoked otoacoustic emissions (TEOAEs) are widely used to screen for hearing loss in neonatal well-baby nurseries. Stimulus frequency otoacoustic emissions (SFOAEs) are widely used as a non-invasive measurement to study cochlear mechanics. Despite progress, there is controversy on where in the cochlea TEOAEs and SFOAEs originate. Aims 1 & 2 will definitively identify the origin along the cochlea of TEOAEs and SFOAEs. Our novel approach is to progressively ablate responses along the cochlear length by slowly injecting ototoxic pharmaceuticals into the cochlear apex. This will provide what no other method has been able to do: remove emission contributions from an OAE's characteristic frequency (CF) place without removing any OAE components that originate far basal (an octave or more higher) of the CF place. The work of Aim 1 & 2 will improve the interpretation of TEOAE-based screening protocols, and advance the understanding of SFOAEs and what they tell us about cochlear tuning and the cochlear amplifier. Aim 3 will study low-frequency sensorineural hearing loss in ears with endolymphatic hydrops. Low-frequency sensorineural hearing loss and endolymphatic hydrops are hallmarks of Mnire's disease that is the focus of high scientific and clinical interest. Our approach uses a new technique that provides an objective measure of low-frequency hearing: the Auditory Nerve Overlapped Waveform (ANOW). ANOW overcomes the long-standing obstacle that conventional electrophysiologic measurements (e.g. otoacoustic emissions and compound action potentials) do not work adequately below ~1 kHz where hearing loss in Mnire's disease occurs. ANOW can detect dysfunction from acute cochlear fluid manipulations that is not detected by conventional measurements, suggesting that ANOW can detect the earliest stages of chronic endolymphatic hydrops. Aim 3 will use ANOW to identify early stages of dysfunction from endolymphatic hydrops before the pathology progresses and can be detected with conventional measures. The proposed studies will expand the knowledge of the origins of physiologic measurements of otoacoustic emissions and hearing loss that is needed to advance basic science studies of cochlear mechanics and clinical diagnosis of hearing loss.
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