The cochlea acts as a nonlinear amplifier that boosts mechanical sensitivity and frequency tuning at low but not high stimulus levels. Although cochlear responses to tones have been well studied, relatively little is known about the dynamic (i.e., time-varying) aspects of this amplification process, such as its delays and associated time constants. These characteristics of the amplifier are especially relevant for understanding details of how dynamic stimuli, such as speech, are encoded by the peripheral auditory system. The proposed research combines the complementary approaches of intracochlear vibrometry, otoacoustic emissions (OAEs), and theoretical modeling to study the dynamics of nonlinear cochlear amplification in animal models. The K99 mentored research will investigate the temporal dynamics and active micromechanics of the amplifier through in vivo vibratory measurements obtained at two locations within the organ of Corti, near the top and bottom surfaces of the outer hair cells?the cellular motors of the cochlear amplifier. Parallel measurements of OAEs will probe their ability to serve as noninvasive assays of the dynamical features of the amplification process. Mathematical models will help to understand the mechanisms of the cochlear amplification delay and its role in shaping OAEs. The R00 independent research will extend the K99-phase findings by further dissecting the mechanisms underlying the dynamical features of cochlear amplification through studies in animals with well- defined damage (acoustic trauma) or abnormality in cochlear structures (transgenic mice). These results are expected to have a high impact because they will be first to reveal the mechanisms underlying the dynamics of cochlear amplification. By relating the OAE results to the vibrometry data in the same animals, the work will establish the utility of OAEs as noninvasive assays of the dynamics of cochlear processing. In the broader context, these data will provide insights into contributions of peripheral processing to temporal phenomena of hearing that degrade with sensory hearing loss and thus will lay the necessary groundwork for developing intervention strategies aimed at restoring auditory processing in the realistic dynamic environments. The K99 phase of the proposed research will aid the candidate?s career development by introducing her to in vivo cochlear vibrometry and by expanding her limited training in mathematical modeling. Together with her extensive background in OAE measurements, these new skills will put the candidate in a strong position to work independently toward her long-term goals of advancing our understanding of cochlear mechanics and exploiting its manifestation in OAE signals to improve noninvasive tests of hearing. The University of Southern California is an outstanding environment for the K99 research because the institution has an active hearing neuroscience community, including the mentors, recognized experts in cochlear mechanics, and other faculty.
(Public Health Relevance Statement) Achieving the long-term goal of greater speech intelligibility in individuals with sensory hearing loss will require detailed knowledge of the deficits in cochlear processing that underlie such perceptual difficulties. The proposed study advances this knowledge by characterizing with direct recordings and modeling studies how the normal and damaged cochlea processes dynamic sounds and how the features of this dynamic processing can be assessed in individuals using noninvasive measurements. Results of the proposed work will help guide the development of new diagnostic tests and treatment strategies (e.g., signal-processing algorithms used in hearing aids) aimed at restoring normal temporal cochlear processing in cases of sensory hearing loss.