The impact of cochlear synaptopahty on brainstem mechanisms of monaural temporal processing and binaural hearing

University Of Colorado Denver, Aurora CO

Investigators

Abstract

PROJECT SUMMARY Binaural hearing allows localization of sounds and confers advantages in complex environments, workplaces, classrooms, etc., where competing speech, noise, and reverberation abound. Unfortunately, an increasing population, spanning infancy through elderly and of diverse etiology, experiences difficulty in such environments despite having normal audiometric thresholds. Such difficulties are a hallmark of auditory processing disorders, or listening difficulties (LDs), which refers to difficulties in processing sound in the central auditory system as demonstrated by poor performance, often specifically in binaural hearing tasks. LDs can emerge from noise exposure, temporary hearing loss, aging, autism, and neurodegenerative diseases. The consequences of LDs can be severe; in children, LDs impact speech and language learning and academic performance and in adults, quality of life, job performance, fitness for duty, etc. Regardless of etiology, a limitation in LDs is that clinical diagnosis is based on a cluster of symptoms, many of which overlap with other disorders such as attention deficit disorder, learning disabilities and language deficits. An additional barrier to diagnosis and development of future treatments to alleviate LDs is that neither the neural mechanisms nor the loci in the auditory system that produce these LDs are yet fully understood. We hypothesize that many LDs are attributable to reductions in peripheral temporal coding that in turn impact binaural processing at the brainstem level. We think binaural hearing is essentially ‘a canary in the coal mine’ for LDs that aren’t associated with audiologically-diagnosed hearing loss. Here we test the hypothesis that two hearing deficits, namely cochlear synaptopathy and extended high frequency hearing loss (EHFL), can cause LDs. The LDs resulting from these deficits are often called “hidden hearing loss” because the hearing impairment is typically hidden from standard audiological assessments. To better identify and treat subjects with such LDs requires understanding the mechanisms that lead to and therefore predict LDs. In this proposal, we hypothesize that noise-induced cochlear synaptopathy causes reduced monaural peripheral temporal coding leading to impaired binaural brainstem function and deficient binaural hearing abilities. The underlying contributions of synaptopathy to LDs are unclear, and there may be confounding/coexisting factors occurring following noise exposure. One suspected factor is loss of hair cells in extended high frequency regions of the cochlea, resulting in EHFL. Therefore, we also study the joint impact of synaptopathy and EHFL. Finally, based on preliminary data we explore the hypothesis that synaptopathy leads to activity-dependent demyelination, due to persistently reduced neural activity, in the brainstem circuits that support initial binaural processing. Because myelin is essential for the precise encoding of temporal information, we hypothesize that even subtle changes in myelin in these circuits can impair binaural processing and thus monaural temporal and binaural hearing ability.