The purpose of this CDA-1 proposal is to provide Dr. Naomi Bramhall with the support and mentorship necessary to make the transition from basic science research to clinical research of noise-induced hearing loss. Dr. Bramhall's previous research has focused on hereditary hearing loss and hair cell regeneration, but as a certified audiologist, she is eager to shift to clinical hearing research. This proposal will provide Dr. Bramhall with the tools and experience necessary to engage in clinical research and generate data which will be used in applying for future funding such as the CDA-2, will guide her path towards independence as a clinical researcher. Her primary mentor for this proposal is Dr. Dawn Konrad-Martin and Dr. M. Charles Liberman is a co-mentor. Loud noise exposure is routinely experienced during military service and hearing loss is the second most common service-related disability among Veterans. Individuals with hearing loss and poor speech discrimination ability often have little success with hearing aids because amplifying sound improves the audibility, but not the clarity, of the speech signal. Loud noise exposure may result not only in damage to outer hair cells, but also lead to auditory neuronal degeneration. Neural loss can result in decreased word recognition (Schuknecht 1994) and may explain why many Veterans have poorer speech discrimination than would be expected based on their ability to detect tones, particularly in noisy environments. Mice show rapid degeneration of auditory nerve peripheral terminals followed by a slow degeneration of spiral ganglion neurons over a period of several months following loud noise exposure, even when their pure tone auditory thresholds recover completely (Kujawa and Liberman 2009). The subpopulation of neurons most vulnerable to noise exposure consists of the low spontaneous rate fibers (Furman et al. 2013), which have a high sensitivity threshold and respond to higher intensity sounds. This neuronal loss is correlated with a decrease in the amplitude of the first wave of the auditory brainstem response (ABR). Age-related reduction in the amplitude of wave I has been demonstrated in humans (Konrad-Martin et al. 2012) and is consistent with temporal bone studies showing auditory neuronal loss with age (Makary et al. 2011), suggesting this metric of auditory neuronal survival is also applicable to humans. Previously, quantification of the degree to which auditory neuronal survival influences speech understanding has been difficult due to limitations in measuring auditory neuronal loss in humans, which could only be accomplished through post-mortem temporal bone studies. The main objectives of this proposal are to use electrophysiological methods to 1) determine if decreased ABR wave I amplitude is associated with noise exposure in humans and 2) examine the impact of noise exposure and decreased wave I amplitude on auditory perception. Our hypothesis is that noise exposure will be associated with decreased wave I amplitude, consistent with animal studies, and that this change will be correlated with decreased speech recognition at high sound levels, difficulty understanding speech in the presence of background noise, and decreased tolerance to loud sounds. Developing the ability to assess auditory neuronal survival with existing clinical tools and advancing our understanding of the specific auditory perceptual deficits resulting from neuronal loss will help guide future treatment options for Veterans suffering from hearing loss.

Public Health Relevance

High noise levels experienced during military service, through use of firearms during combat or basic training or from close proximity to aircraft or other loud machinery, puts Veterans at an increased risk of developing hearing loss. Hearing loss is one of the most common service-related disabilities and can have a profound effect on communication ability. Although hearing aids (HA) can ameliorate the condition, many individuals fit with HA still experience difficulty understanding speech. Recent animal studies suggest this may be due to auditory neuronal degeneration resulting from noise exposure. We propose to look for a similar phenomenon of noise-induced neuronal degeneration in humans using auditory electrophysiology as an indicator of neuronal damage. We will also investigate the impact of noise-related electrophysiological changes on auditory perception.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Veterans Administration (IK1)
Project #
5IK1RX001484-03
Application #
9172208
Study Section
Career Development Program - Panel I (RRD8)
Project Start
2014-08-01
Project End
2016-10-31
Budget Start
2016-08-01
Budget End
2016-10-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Portland VA Medical Center
Department
Type
DUNS #
089461255
City
Portland
State
OR
Country
United States
Zip Code
97239