Place and Time Processing of Pitch in the Context of Cochlear Dysfunction

文摘:

Abstract: Sensorineural hearing loss occurs in 15% of American adults and current treatment protocols are often guided by limited and archaic diagnostics. Not all types of sensorineural hearing loss are identical in physiology and a major priority of current auditory research is to innovate in the space of precision auditory diagnostics and treatments. Understanding how specific patterns of damage to the cochlea or auditory nerve variably impair the perception of different sound features is critical to improve treatments for hearing-impaired individuals. The history of auditory research has led to considerable insight as to how anatomic components of the auditory periphery, namely inner hair cells (IHCs), outer hair cells (OHCs), and the cochlear synapse function together to transduce, amplify, and code simple sounds. However, there exists considerable gaps in our knowledge of how these peripheral components are responsible for maintaining the fidelity of more complex auditory phenomena and perception. Pitch, the perceived “highness” or “lowness” of a given sound, is an example of a complex psychoacoustic phenomenon. Pitch cues are used to listen to and compose music and to process vowels, identify talkers, and convey emotion. Without intact pitch perception, conversation becomes emotionless, a symphony becomes a cacophony. While pitch has been extensively studied perceptually, our knowledge of the underlying neurophysiology of pitch remains mostly hypothetical. Three categories of pitch theories attempt to explain pitch coding in terms of the tonotopic organization of our auditory system (place), the temporal information present in neural firing patterns (time), or a combination of these (place-time). We plan to assess these theories in the context of cochlear pathologies that are expected to differentially alter place and timing cues, hence developing a more comprehensive understanding of pitch. Based on the literature, our central hypothesis is that deficits in time and place coding both affect the neural coding and perception of pitch, but with distorted place coding playing a stronger role. We will test this hypothesis by using animal models of OHC, IHC, cochlear synapse damage, and Distorted Tonotopy to investigate SNHL effects on pitch-related electrophysiology (Aim 1). OHC damage primarily disrupts place cues, while IHC and cochlear synapse damage alter timing cues. We will then compare this animal electrophysiology to identical measures in humans with normal and impaired hearing, evaluating the implications on behavioral pitch discrimination (Aim 2). Finally, we will develop four statistical models to identify how variations in pitch coding and perception are predicted by non-invasive assays of hearing loss and profiles of SNHL (Aim 3). This cross-species approach moves the field forward by testing well- established pitch theories in the context of SNHL and by opening doors to better identifying the functional consequences of individual variations in hearing ability. Overall, the cross-species design of the proposed work will develop my potential as a physician-scientist, strengthening my ability to design translational experiments that use ideal laboratory models of neurological disorders to predict clinically relevant outcomes.