Presbycusis (age-related hearing loss), the number one communicative disorder in our aged population, is characterized by reduced ability to hear ambient sounds and difficulty understanding speech, especially in background noise. The Specific Aims of this grant focus on important remaining areas of enquiry regarding the neural bases of presbycusis. In the past decade noteworthy advances have been made in our neuroscientific understanding of the etiologies of presbycusis. For example, key distinctions have been discovered concerning the specialized roles of the ear and the brain and how they interact as one ages. These peripheral and central auditory factors result in two main perceptual difficulties: a loss in sensitivity biased toward the higher frequencies critical for understanding speech, and a serious reduction in the ability to understand speech in noise. Moreover, temporal processing problems, that have been linked to speech perception-in-noise difficulties of the aged, have been shown to partly reside in auditory brainstem circuitry. Theoretical interventions may lie on the horizon, however, additional aspects of the neural bases of presbycusis must be investigated before such undertakings will be successful. Specifically, further delineation is required regarding functional aspects of neural etiologies underlying age-related declines in a) the auditory brainstem inhibitory system, b) neuromodulatory components of the central auditory system, c) the auditory efferent system - that we recently demonstrated start in middle age, d) sound spatial localization abilities and age-related loss of speech perception in noise, and e) the molecular biology of neuronal channels in age-related hearing loss. In the next grant period, we propose a set of synergistically related human and animal experiments attacking theses issues. The adminstrative and animal cores will serve four multidisciplinary projects with experimental approaches ranging from audiology, speech perception, psychoacoustics and psychophysics in humans, to startle reflex, neurophysiology, evoked potentials, single unit physiology, neuroanatomy, immunohistochemistry, distortion product otoacoustic emissions, and molecular biology in animals. The primary long-term goal of the program project is to develop biomedical interventions that prevent or cure sensorimotor disorders in our aging population.