PROJECT SUMMARY Hearing is an active process that works in concert with vision. How and where the active processes in hearing contribute to interactions with vision is presently unknown. One possibility is that these interactions occur at the earliest stages of the auditory pathway – within the ear. Several types of physical actuators located inside the ear, namely the middle ear muscles and outer hair cells, collectively adjust eardrum motion and generate endogenous, subthreshold sounds known as otoacoustic emissions. We recently discovered a new type of such sounds: eye movement-related eardrum oscillations, or EMREOs. This discovery implicates the ear’s internal actuation systems in a form of multimodal processing. However, the mechanism that generates EMREOs is presently unknown. Understanding this mechanism will shed light on the functional consequences of eye movements for hearing and how hearing coordinates with vision. We will test the contributions of these actuators to EMREOs in an animal model, selectively interrupting each component surgically or via local application of ototoxic substances. We will compare the results of these studies to results obtained in human hearing loss patients suffering from middle ear muscle or outer hair cell dysfunction. We hypothesize that the middle ear muscles and outer hair cells work in concert to produce the EMREO, and that dysfunction of any of the actuator systems will lead to anomalies in EMREOs. Possible perceptual consequences of such dysfunction will also be probed. Together, these experiments will shed light on how the brain adjusts the auditory transduction system when eye movements shift the relative alignments of the eyes and ears. That oculomotor signals occur at the very gateway of the auditory pathway represents a fundamental shift in our understanding of the scope and mechanisms employed in hearing, and in particular how the auditory system interfaces with the visual system. The findings will be relevant to a variety of hearing disorders involving the ears’ internal actuators or their top-down control, including sensorineural hearing loss and age-related hearing loss, as well as complex sensory/cognitive syndromes such as dyslexia and autism.