Research Project
10222641
Overall Project Summary New insights from animal studies of noise-induced and age-related hearing loss suggest that the most vulnerable elements in the inner ear are the synaptic connections between hair cells and sensory neurons. This primary neural degeneration, also called cochlear synaptopathy, does not elevate thresholds. Thus, it can be widespread in ears with intact hair cell populations and normal audiograms, where it has been called ?hidden? hearing loss. It likely contributes to difficulties understanding speech in a noisy environment and may be an instigating factor in the generation of tinnitus and hyperacusis. Cochlear synaptopathy may also be widespread in acquired sensorineural hearing loss of other etiologies and degrees of hair cell damage. Thus, it may be a major contributor to the well-known differences in auditory performance among people with identical audiometric patterns of ?overt? hearing loss. Our Research Center aims to take these paradigm-shifting ideas from animal models to human subjects. Based on the synthesis of many research threads from the study of overt and hidden hearing loss, we have devised a set of physiological, electrophysiological and psychophysical tests of hearing and cochlear function that we believe are most powerful in the diagnosis and understanding of cochlear synaptopathy in human subjects. In Project 1, we apply this test battery to gerbils exposed to noise or ototoxic drugs and test their diagnostic power by directly measuring the underlying cochlear histopathology in cases of overt or hidden hearing loss. In Project 2, we use immunostaining to directly assess the prevalence of cochlear synaptopathy in human temporal bones from subjects with overt or hidden hearing loss with a range of etiologies. In Project 3, we study hidden hearing loss in college students by applying the test battery to subjects with normal audiograms but a broad range of reported and measured sound exposures. In Project 4, we assess older adults with overt hearing loss by applying the tests to a subject pool with carefully matched down-sloping audiograms and by characterizing training-based improvements in speech-in-noise performance as reflected at different peripheral, brainstem, midbrain and cortical levels. Our preliminary studies of young adults show clear signs of hidden hearing loss in a group with repeated exposure to high-level music, suggesting the importance of this phenomenon to the public health. The success of neurotrophin-based approaches to the treatment of cochlear synaptopathy in animal models suggests that therapies may be on the horizon. Thus, the need for better understanding of the prevalence, diagnosis and functional consequences of cochlear synaptopathy is clear.
