Project Summary/Abstract Sensorineural hearing loss (SNHL) in military personnel is commonly caused by noise- or blast-related damage to the auditory periphery (cochlea) and/or the central system, which includes changes in the integrity of the cochlear partition and cellular death along the auditory pathway. Hearing loss is often permanent, and there exist no cures for sustained injuries. The current proposal seeks to characterize the signal processing along the auditory pathway by establishing the structure-function relationship in both normal ears and with various types of SNHL. The overall goal is to improve the diagnosis of SNHL within the clinic by separating contributions from cochlear (sensory) and retro-cochlear (neural) loss. We will combine a novel, state-of-the-art measurement technique (optical coherence tomography, OCT) with recordings that are already available in the clinic [i.e., distortion product otoacoustic emissions (DPOAE) in the ear canal and frequency-following responses (FFR) from the cortex] so that the cochlear mechanics and the detrimental effects of noise- or blast- exposure can be evaluated at different stages along the auditory pathway. As of now, OCT measures from the cochlea cannot be recorded from humans, but we expect that the combination of DPOAE and FFR provides a differential diagnosis of SNHL that distinguishes damage of the sensory versus neural component. Aim 1 of this proposal will form the foundation of the study by determining how DPOAEs and FFRs relate to cochlear micromechanics in normal gerbil ears. The experimental results will be used to develop a Best Approximation Model (BAM) that will predict cochlear function using DPOAEs and FFRs. In Aim 2 we will explore how various forms of SNHL change the underlying cochlear mechanics with the specific design to differentially diagnose sensory and neural hearing loss and establish how these changes can be quantified using a combination of DPOAE and FFR measurements. These results will further validate the BAM developed under Aim 1. In Aim 3 we will apply the knowledge obtained in animals to humans that suffer from different types of SNHL to improve the clinical differential diagnosis of an SNHL using DPOAEs, FFRs, and the BAM. Using direct and simultaneous measurements along the auditory pathway, the signal processing under these conditions will be quantified in detail. The proposed research will advance our understanding of sound processing within the auditory system, especially at low frequencies that are important for speech and provide critical information to improve our ability to diagnose and develop new treatments for SNHL. This will benefit our Veterans, many of whom suffer from noise/blast-induced hearing loss.