Role of Organ of Corti Outer Hair Cell/Vibration Hot Spots in Distortion Product Otoacoustic Emission Generation

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PROJECT SUMMARY/ABSTRACT Earlier research in our laboratory using interference tones (ITs) and vector-difference analyses between control and various experimental conditions established that large distortion product otoacoustic emissions (DPOAEs) components evidenced by strong enhancement and/or suppression, can arise from regions located up to several octaves basal to the f2 primary-tone. The proposed experiments in gerbils are focused on identifying a physical mechanism in cochlear micromechanics that explains the existence of such basal DPOAE components. Specifically, the studies described below are aimed at showing that basal components are produced by recently described nonlinear vibration hotspots (VHSs) that localize to the outer hair cell (OHC) region. These OHC/VHSs, unlike the BM, are nonlinear over many octaves below the measurement BF, and are capable of generating physical motions significantly larger than their counterpart BM vibrations. Methods will utilize noninvasive optical coherence tomography (OCT) that is capable of measuring vibrations of various subcomponents of the organ of Corti, along with the simultaneous recordings of intracochlear distortion products (iDPs) and ear-canal DPOAEs. In this manner, OHC/VHSs will be linked to the nonamplifying widely distributed nonlinearity hypothesized to be the source of basally generated DPOAE components, thus, providing a direct physical mechanism for their generation. Briefly, Aim 1 utilizes OCT to characterize iDPs from the BM and OHC/VHS regions simultaneously as a function of primary-tone levels and f2/f1 ratios as the primary-tones are stepped apically past the best frequency (BF) of the OCT-measurement location. Fourier transforms of the vibrations from the BM and the OHC/VHSs will be performed to extract iDPs from these subcomponents. Next, ITs and brief noise overexposures will be used to linearize the nonamplifying nonlinearity of the OHC/VHSs while simultaneously measuring ear-canal DPOAEs. Vector subtraction will be used to isolate components that are hypothesized to be responsible for generating basal DPOAE components. In Aim 2, furosemide administration will be employed to temporarily eliminate OHC/VHSs and BM iDPs, thereby interfering with both the broadly distributed OHC/VHS nonlinearity and the BM amplifying peak nonlinearity, which have been shown to exhibit different recovery-time courses. In this manner, contributions from the BM peak and broadband nonlinearities can be separated. Again, basal iDP and DPOAE components will be extracted by vector subtraction of these measures before and after the above interventions. The expected outcomes of these experiments will clarify under what circumstances OHC/VHSs produce iDPs and to what extent they contribute to the DPOAEs commonly recorded in the ear canal. If the proposed experiments are successful, by providing a direct physical mechanism for the generation of basal DPOAEs, decades of theoretical models of DPOAE generation will require significant modification and clinical DP-grams can be improved by removing the confounding basal DPOAE components with an IT.     1