This proposal to examine classic indicators of sensorimotor gating - the acoustic startle response (ASR) and prepulse inhibition (PPI) - in humans with tinnitus and hyperacusis is both important and timely. It is motivated by (i) the almost complete absence of data on either ASR or PPI in relation to human tinnitus or hyperacusis, despite the success of these measures in objectifying and elucidating a variety of other conditions also thought to involve failures of inhibition and over-excitation, including schizophrenia, obsessive compulsive disorder and Tourette's syndrome, (ii) suggestions that enhanced ASR in animal models indicates hyperacusis, but a lack of data testing this hypothesis and, (iii) the recent surge of interest in a gap-detection startle reflex (GDSR) test fo tinnitus in animals, which has yet to be validated in humans and is reliant on the ASR and neural circuitry mediating PPI. The proposed experiments measuring ASR, PPI and GDSR in human subjects will test (1) whether insights into the mechanisms of tinnitus and hyperacusis might be leveraged from other more heavily studied neurological conditions for which the ASR and PPI are already well-characterized, and (2) whether ASR and GDSR measures thought to indicate hyperacusis and tinnitus in animals actually do. The proposed work is crucial to understanding clinical tinnitus and hyperacusis and, specifically, relating it to animal data on th underlying neural mechanisms of these increasingly prevalent disorders.
The proposed work moves into largely unexplored territory by examining the acoustic startle response (ASR) and prepulse inhibition (PPI) in humans with tinnitus and hyperacusis. The work will test whether insights into the mechanisms of tinnitus and hyperacusis might be leveraged from other more heavily studied neurological conditions for which the ASR and PPI are already well-characterized. ASR/PPI-based measures thought to indicate tinnitus and hyperacusis in animals will be tested in humans, thus building a bridge between clinical tinnitus/hyperacusis and animal data on the underlying neural mechanisms of these disorders.
|Plotkin, Scott R; Ardern-Holmes, Simone L; Barker 2nd, Fred G et al. (2013) Hearing and facial function outcomes for neurofibromatosis 2 clinical trials. Neurology 81:S25-32|