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Principal Investigator: Andrew Sivaprakasam
Organization: PURDUE UNIVERSITY
Fiscal Year: 2024
Award: $53,974
Funding agency: National Institute on Deafness and Other Communication Disorders
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.
Terms: <21+ years old><Acoustic Nerve><Acoustic Trauma><Adult><Adult Human><Affect><Age><American><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Animals><Assay><Assistive Technology><Auditory><Auditory system><Behavioral><Bioassay><Biological Assay><Categories><Cellular injury><Chinchilla><Chinchilla (genus)><Cochlea><Cochlear Hearing Loss><Cochlear Nerve><Cochlear Organ><Cochlear Root of Acoustic Nerve><Cochlear Root of Eighth Cranial Nerve><Code><Coding System><Cognitive Discrimination><Communication><Complex><Corti Cell><Cranial Nerve Eight><Cranial Nerve VIII><Cues><Cyclicity><Data><Diagnosis><Diagnostic><Difference Limen><Differential Threshold><Discrimination><Dysfunction><Eighth Cranial Nerve><Electrophysiology><Electrophysiology (science)><Emotions><Experimental Designs><Frequencies><Functional disorder><Hair Cells><Health><Hearing><Hearing Loss><History><Human><Hypoacuses><Hypoacusis><Impairment><Individual><Individual Differences><Inner Hair Cells><Inner ear hair cells><Intuition><Investigation><Knowledge><Laboratories><Link><Literature><Measures><Modeling><Modern Man><Music><Nerve Fibers><Nervous System Diseases><Nervous System Disorder><Neural Transmission><Neurologic Disorders><Neurologic Models><Neurological Disorders><Neurological Models><Neurophysiology / Electrophysiology><Outcome><Outer Hair Cells><Pathology><Pathway interactions><Pattern><Perception><Periodicity><Peripheral><Physicians><Physiologic><Physiological><Physiology><Physiopathology><Pitch Discrimination><Pitch Perception><Play><Probabilistic Models><Probability Models><Process><Protocol><Protocols documentation><Psychoacoustics><Recording of previous events><Reflex><Reflex action><Research><Research Training><Rhythmicity><Role><Scientist><Self-Help Devices><Sensorineural Deafness><Sensorineural Hearing Loss><Sensory Hearing Loss><Statistical Models><Stimulus><Synapses><Synaptic><Synaptic Transmission><Tail><Techniques><Testing><Time><Treatment Protocols><Treatment Regimen><Treatment Schedule><VIIIth Cranial Nerve><Variant><Variation><Vestibulocochlear Nerve><Voice><Work><adulthood><ages><animal data><assisted device><assistive device><auditory nerve><auditory trauma><aural muscle><base><bases><behavior measurement><behavioral measure><behavioral measurement><cell damage><cell injury><cell transduction><cellular damage><cellular transduction><clinical predictors><clinical relevance><clinically relevant><cochlear hearing impairment><cochlear synaptopathy><damage to cells><design><designing><dysfunctional hearing><ear hair cell><ear muscle><electrophysiological><experiment><experimental research><experimental study><experiments><falls><good hearing><healthy hearing><hearing challenged><hearing defect><hearing deficient><hearing deficit><hearing difficulty><hearing dysfunction><hearing impairment><hearing trauma><histories><human data><human subject><improved><individual heterogeneity><individual variability><individual variation><injury to cells><innovate><innovation><innovative><insight><intuitive><mid life><mid-life><middle age><middle aged><middle ear><midlife><model of animal><neural><neural correlate><neurological disease><neurophysiological><neurophysiology><normal hearing><otoacoustic emission><pathophysiology><pathway><response><sensorineural hearing impairment><skills><social role><sound><statistical linear mixed models><statistical linear models><synapse><synapse function><synaptic function><theories><transduced cells>