The complex genetic and environmental factors affecting human hearing over the lifespan contribute to a large variation in audiometric profiles and suprathreshold measures of auditory function. As a result, determining mechanisms of age-related hearing loss in older adults is challenging because genetic, age, noise history, injury, disease, medication, diet, and other factors can work independently and jointly to alter human auditory function. Although morphologic findings from older humans are limited to postmortem data, experimental procedures with animals of known heredity can disrupt specific cochlear systems, model certain pathologic conditions, and introduce or minimize environmental exposures, while measuring subsequent changes in auditory function. Consistent with results from animal models linking audiometric profiles to specific cochlear pathologies, such as metabolic or sensory loss, audiograms from the Clinical Research Center's human subject database (Core B) were classified into four audiometric phenotypes, which provided a means to characterize the pathophysiology of hearing loss in older humans. Audiometric phenotypes determined using supervised machine learning classifiers were consistent with expected demographic and noise history patterns that segregate with patterns of hearing loss. Project 1 will refine and further validate these phenotyping methods using suprathreshold measures of cochlear and neural function beyond the audiogram that characterize metabolic and sensory presbyacusis, and the additive effects of morphologic and functional neural loss. To meet this goal.
Aim 1. 1 tests the hypothesis that older adults with metabolic and sensory presbyacusis differ in cochlear nonlinearities and lower frequency suprathreshold auditory function.
Aim 1. 2 tests the hypothesis that changes in auditory nerve activity result in unique and additive effects in older adults with metabolic and sensory presbyacusis. Thus, Project 1 will assess age related changes in auditory function related to metabolic, sensory, and neural pathologies and link findings to Project 2, focused on central auditory and cortical changes, and to translational Projects 3 and 4, which will determine the genetic and cellular mechanisms of age-related hearing loss using humans and human tissue. With these approaches, morphologic and physiologic changes characterizing metabolic, sensory, and neural presbyacusis provide a framework for assessing and interpreting age-related changes in human auditory function.

Public Health Relevance

Knowledge of the variations in pathophysiology underlying human age-related hearing loss may dictate different diagnostic test batteries, hearing-aid fitting algorithms, auditory-training regimens, and recommendations for communication strategies. This new information will lead to better diagnosis and treatments for this high-prevalence public health concern, and improved communication and quality of life for millions of older adults

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Specialized Center (P50)
Project #
5P50DC000422-29
Application #
9205505
Study Section
Special Emphasis Panel (ZDC1)
Project Start
Project End
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
29
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
Lewis, Morag A; Nolan, Lisa S; Cadge, Barbara A et al. (2018) Whole exome sequencing in adult-onset hearing loss reveals a high load of predicted pathogenic variants in known deafness-associated genes and identifies new candidate genes. BMC Med Genomics 11:77
Bologna, William J; Vaden Jr, Kenneth I; Ahlstrom, Jayne B et al. (2018) Age effects on perceptual organization of speech: Contributions of glimpsing, phonemic restoration, and speech segregation. J Acoust Soc Am 144:267
Panganiban, Clarisse H; Barth, Jeremy L; Darbelli, Lama et al. (2018) Noise-induced dysregulation of Quaking RNA binding proteins contributes to auditory nerve demyelination and hearing loss. J Neurosci :
Chiarello, Christine; Vaden Jr, Kenneth I; Eckert, Mark A (2018) Orthographic influence on spoken word identification: Behavioral and fMRI evidence. Neuropsychologia 111:103-111
Harris, Kelly C; Vaden Jr, Kenneth I; McClaskey, Carolyn M et al. (2018) Complementary metrics of human auditory nerve function derived from compound action potentials. J Neurophysiol 119:1019-1028
McRackan, Theodore R; Fabie, Joshua E; Burton, Jane A et al. (2018) Earphone and Aided Word Recognition Differences in Cochlear Implant Candidates. Otol Neurotol 39:e543-e549
Dubno, Judy R (2018) Beyond the audiogram: application of models of auditory fitness for duty to assess communication in the real world. Int J Audiol 57:321-322
McRackan, Theodore R; Clinkscales, William B; Ahlstrom, Jayne B et al. (2018) Factors associated with benefit of active middle ear implants compared to conventional hearing aids. Laryngoscope 128:2133-2138
Dias, James W; McClaskey, Carolyn M; Harris, Kelly C (2018) Time-Compressed Speech Identification Is Predicted by Auditory Neural Processing, Perceptuomotor Speed, and Executive Functioning in Younger and Older Listeners. J Assoc Res Otolaryngol :
Worley, Mitchell L; Schlosser, Rodney J; Soler, Zachary M et al. (2018) Age-related differences in olfactory cleft volume in adults: A computational volumetric study. Laryngoscope :

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