Behavioral evidence of tinnitus and its correlation with ABR wave metrics in chinchilla induced by blast injury. Program Description: Neurophysiology of cognition/Neuronal computation
Abstract
Tinnitus is a very commonly reported injury following blast by military personnel (VBA Annual Report, 2016). We lack sufficient understanding of mechanisms leading to the development of chronic tinnitus (International State of Science Meeting on Blast-Induced Tinnitus (2011). Several theories, and some empirical data, suggest that a reduction in peripheral auditory nerve input to the brainstem following acoustic trauma can lead to tinnitus. However, to date, there is no experimental evidence that peripheral deafferentation (now popularly known as cochlear synaptopathy) causes tinnitus. Several research groups are actively investigating the relationship among tinnitus, cochlear synaptopathy and auditory brainstem response (ABR) dependent variables such as wave I amplitude. To date, no clear direct relationship between noise exposure and tinnitus in an animal model has emerged, and to the PIÕs knowledge, this relationship has not been investigated in animals following blast exposure. To pursue such a relationship, behavioral evidence of tinnitus in an animal model following blast injury is needed. The identification of tinnitus in an animal model, combined with a non-invasive biomarker (such as ABR wave I amplitude, which can be measured in both humans and non-humans) will allow the generalization of invasive neurophysiological measures in the animal model to humans. This will also allow a more conclusive investigation as to whether synaptopathy leads to tinnitus. In this proposal, whether one or more levels of blast exposure leads to tinnitus in the chinchilla will be determined. Chinchilla is more clinically relevant and is an optimal animal model for investigating the presence of tinnitus post blast because of their good low frequency hearing (as the acoustic blast has most of its energy below 2000 Hz), the ability to train chinchillas to perform various psychophysical tasks, and the rich experimental history of using the chinchillas to investigate noise induced hearing loss, both to continuous stimuli and to impulse noise. Gap-prepulse inhibition of acoustic startle (GPIAS) has been used to investigate tinnitus, as it does not necessitate behavioral manipulation, training, motivation & is resistant to extinction in animals (Turner et al., 2006). Thus, GPIAS seems to be well suited for studies that investigate mechanisms of tinnitus development. Hence, we hypothesize that measuring blast-induced tinnitus in chinchillas using GPIAS would provide a reliable platform to investigate changes in peripheral auditory information processing causing tinnitus. In this study, we propose to characterize the behavioral evidence of blast-induced tinnitus in chinchillas using PreyerÕs reflex (flexion of pinna) as a reliable marker of the startle response (as shown in Guinea pigs, Berger et al., 2013) along with whole body movement and by adopting a new statistical approach (Schilling et al., 2017), rather than by simple averaging of measured pre-pulse inhibition (PPI) values. It is accomplished by following specific aims. Specific aim 1: To determine the optimal level of blast exposure, i.e., the level that produces a modest threshold shift (as measured using tone burst ABRs) and to relate ABR wave-I amplitude to blast level, ABR threshold shift and tinnitus presence. Specific aim 2: To compare the results of tinnitus assessment using both PreyerÕs reflex and whole body movement using the gap pre-pulse inhibition paradigm in chinchillas. This study characterizing psychophysical evidence of blast-induced tinnitus is innovative for tinnitus research as the outcome of the proposed study could provide strong evidence for the reliability of GPIAS for tinnitus assessment in chinchilla using PreyerÕs reflex. Thus, this study would set the stage for more in-depth neurophysiological studies to investigate if primary neural degeneration underlies central gain of sub-cortical areas responsible for tinnitus percept.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 09, 2020
- Source ID
- W911NF2010251
Entities
People
- Muthaiah Krishnan
Organizations
- Army Contracting Command
- United States Army
- University at Buffalo