PROJECT SUMMARY/ABSTRACT Endolymphatic hydrops (EH), a hallmark of Ménière’s Disease, is a cochlear disease caused by either an over- production or under absorption of endolymphatic fluid. As a result of this excess of endolymph, the membranes bounding the endolymphatic space are distended outwards. These notable alterations in cochlear morphology cause disruptions in cochlear mechanics. The early identification and monitoring of EH is critical to preventing progression of this, oftentimes, debilitating auditory/vestibular disease (which is episodic in nature). Clinical diagnosis of EH is primarily made via symptomology, with the most reliable diagnostic marker being a fluctuating, low-frequency sensory hearing loss. EH typically progresses to sensory deficits that no longer recover, resulting in permanent hearing impairment that can eventually span across the audible frequency range. Therefore, early identification and monitoring of the disease process is critical to preventing its progression. Otoacoustic emissions (OAEs) are an ideal monitoring tool. OAEs are low-level sounds measured in the ear canal that have been shown to gauge cochlear function and dysfunction with high accuracy. Along with recent advances in this objective, efficient, and noninvasive probe of cochlear function, OAEs have the potential to be a powerful tool in improving the efficacy of EH diagnosis, given the human cochlea cannot be accessed or manipulated for direct study. We can now measure two distinct classes of emissions jointly — OAEs arising from nonlinear distortion (distortion product OAEs) and OAEs arising from coherent linear reflections (stimulus- frequency OAEs) using rapidly sweeping tones. The purpose of this work is to assess the diagnostic utility of such a Joint-OAE Profile in identifying and monitoring EH while also exploring the mechanism of disease through perceptual tests and phenomenological modeling to improve the efficacy of EH diagnosis in humans. This K01 proposal will first probe cochlear changes during EH using a Joint-OAE profile – a profile comprised of the two classes of emissions measured and analyzed together to access both generation processes (Aim 1). Additionally, we will explore the underlying mechanisms of EH by determining whether EH causes shifts in the cochlear frequency-place map using both a perceptual task (binaural pitch matching between the healthy and diseased ear within an individual) and physiological measurements of SFOAE latency (or group delay) (Aim 2). Finally, data collected from Aim 1 and 2 will be directly compared to model predictions that explore the mechanical effects of EH on the cochlear partition and the consequences for OAE generation (Aim 3). Combined, this physiological, perceptual, and computational approach to understanding endolymphatic hydrops is a comprehensive and bold attempt to understand its clinical manifestations and disease timeline, as well as its underlying mechanisms of pathology.