Validating an Animal Model of Hyperacusis
By Kelly Radziwon, Ph.D.
Hyperacusis is a debilitating hearing condition in which normal everyday sounds are perceived as exceedingly loud, annoying, aversive, or even painful. The prevalence of hyperacusis approaches 10 percent, making it an important but understudied medical condition. To learn what is happening in the brain and nervous system when hyperacusis is present, we used sound-evoked, functional magnetic resonance imaging (fMRI) to locate regions of abnormal activity in the central nervous system of rats with behavioral evidence of hyperacusis induced with an ototoxic drug (sodium salicylate). We observed enhanced central auditory gain and were able to confirm this electrophysiologically.
This graph shows reaction time measurements in the rat model. Initial baseline measurements were acquired without any drug administration. In the weeks following, saline or the ototoxic drug sodium salicylate was administered and reaction times measured. Salicylate reduces reaction times at high sound pressure levels, providing behavioral evidence of hyperacusis.
As published in Hearing Research in April 2020, our results demonstrate for the first time that noninvasive, sound-evoked fMRI can be used to identify regions of neural hyperactivity throughout the brain in an animal model of hyperacusis. In addition, we showed we can experimentally manipulate the degree and type of hearing loss and to objectively quantify biomarkers of hyperacusis that may be used for clinical diagnosis.
One significant impediment of using fMRI to investigate hyperacusis in humans is that hyperacusis patients cannot tolerate the loud sounds generated by MRI scanners. Sound protective devices offer some relief, but an advantage to using mice and rats for these studies is that they have poor low-frequency hearing in regions where there is considerable scanner noise and are not as affected by it. Overall this study allows us to connect human fMRI data with data from the animal model, advancing a greater understanding of hyperacusis.
A 2015 and 2018 ERG scientist funded by Hyperacusis Research Ltd., Kelly Radziwon, Ph.D., is a research assistant professor in the department of communicative disorders and sciences at the University at Buffalo, State University of New York.
In addition, Radziwon and colleagues, including Senthilvelan Manohar, Ph.D. (a 2017 Hyperacusis Research-funded ERG recipient) and Richard Salvi, Ph.D. (a 1978–79, 1988, 1990–92 ERG scientist), contributed the chapter “Preclinical Animal Behavioral Models of Hyperacusis and Loudness Recruitment” in the book “New Therapies to Prevent or Cure Auditory Disorders,” published by Springer in March 2020.