Observations in the military have shown that exposure to battlefield-related noise can cause balance disorders characterized by postural instability, dizziness, and vertigo; however, underlying mechanisms are not well understood. One reason for this knowledge gap may be that most previous assessments have been focused on evaluation of horizontal semicircular canal function. Recent animal and human studies, however, provide evidence that noise overstimulation impacts the sacculus; the vestibular end-organ closest to cochlea, to a much greater extent than any of the other vestibular sensory receptors (Akdogan et al., 2009; Akin et al., 2012). New developments in the use of cervical and ocular vestibular evoked myogenic potentials combined with video head impulse testing, now allow all five vestibular sensory organs (three semicircular canals and two otolith end organs - utricle and saccule) to be assessed in a comprehensive manner that allows the functional integrity of each to be differentiated. This novel test battery allows assessment in a rapid and non-invasive manner following noise exposure. The underlying hypothesis of the proposed studies is that a noise sufficient to induce hearing loss can also induce dysfunction in the sacculus, often without effects on other vestibular end-organs. This will be tested in Veterans with noise-induced hearing loss and in the rat, with the animal studies able to define and control the noise exposure conditions. The use of parallel human and animal studies provides the ability to correlate specific cellular damage (from animal studies) with the noise-induced dysfunction (found in both the human and animal investigations) as well as to identify underlying molecular mechanisms that could point to therapeutics for treatment. Manganese enhanced magnetic resonance imaging (MEMRI) is a powerful imaging modality used to map and assess whether a central nervous system pathway remains intact following insult and to determine changes in activity following peripheral damage (Pautler, 2004, 2006; Holt et al., 2010; Cacace et al., 2014). We hypothesize that sacculus evoked central vestibular activity will change following noise overstimulation.
Specific Aim 1 : Test the hypothesis that noise that causes permanent threshold shifts in hearing sensitivity will also cause vestibular dysfunction in the sacculus with less effet in the utricle and semicircular canals in humans and in animals.
Specific Aim 2 A: Test the hypothesis that noise that causes moderate loss of cochlear outer hair cells will also cause loss of vestibular hair cells and calyceal vestibular nerve connections and this loss will primarily be found in the sacculus with less effect in the utricle or semicircular canals.
Aim 2 B: Test the hypothesis that noise overstimulation that causes increased free radical formation in cochlear sensorineural epithelium will cause a similar increase in the sacculus.
Specific Aim 3 : Test the hypothesis that noise that causes moderate loss of cochlear outer hair cells will also cause changes in neuronal activity within the sacculus-associated central vestibular pathways.
of the Proposed Work to the VA Patient Care Mission. Noise-related auditory dysfunction is the most common service-connected condition in Veterans. Although the impact of noise on hearing is well known, less is understood about the effects of noise on vestibular and balance function. Interest in this area has been driven by observations in the military suggesting that battlefield-related noise can cause balance disorders characterized by vertigo, dizziness, and postural instability. Symptoms of dizziness and imbalance can impact safety and reduce quality of life for Veterans. Our proposed studies will test for the underlying cause and mechanisms of noise-induced vestibular dysfunction in parallel human and animal studies. The results will improve the ability to identify and diagnose these problems with the long term goal of developing novel therapeutics to prevent and treat noise related vestibular dysfunction.
