The information about head motion and orientation provided by the vestibular labyrinth is constrained by several features, but the brain is still abl to generate relatively accurate perceptual and eye movement responses during vestibular stimulation. One major problem the vestibular system must deal with is the noise inherent in all aspects of neural processing. In this proposal we will use several novel techniques (including vestibular psychophysics in non-human primates, high-frequency electrical stimulation of semicircular canal afferents, and measures of the vestibulo-ocular reflex (VOR) threshold and central vestibular noise) to investigate how noise affects the central processing that is responsible for vestibular-mediated eye movement and perceptual responses. More specifically, we propose three hypotheses which we will test in three specific aims that focus on the brain's ability to optimize perceptual and eye movement responses despite the limitations in the information provided by the labyrinth. In the first two specific aims, we will vary the amount of noise on the canal afferent signals by using very high-frequency electrical stimulation of the canal ampullary nerves superimposed on the normal canal afferent cues. We will investigate how noise on the canal rotational inputs affects perceptual and eye movement responses, and predict that when the noise increases the velocity storage integrator in the brain will become less effective (aim 1) and that the misperception of low-frequency translation as tilt will be accentuated (aim 2).
In specific aim 3, we will investigate the hypothesis that peripheral vestibular ablation increases central vestibular noise by inducing different degrees of peripheral vestibular hypofunction with aminoglycosides and measuring changes in the VOR and in a behavioral measure of vestibular noise, based on changes in the variance of eye velocity during fixation of a punctate target with the head stationary. In sum, these experiments will help answer longstanding and fundamental questions about how vestibular information is processed centrally, and this work will not only improve understanding of normal vestibular physiology but may also help elucidate the mechanisms responsible for the abnormal perceptual and eye movement responses that occur with disorders of the peripheral and central vestibular system.

Public Health Relevance

This project will investigate the mechanisms used by the brain to optimize perception of head motion and orientation and eye movement responses despite the noise that is present in all aspects of neuronal processing. The goal is to improve understanding of normal vestibular physiology, which should help to elucidate the mechanisms responsible for the abnormal perceptual and eye movement responses that occur in patients with disorders of the vestibular system in the inner ear or in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC013069-05
Application #
9388976
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Poremba, Amy
Project Start
2013-12-01
Project End
2019-11-30
Budget Start
2017-12-01
Budget End
2019-11-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
Dahlem, Kilian; Valko, Yulia; Schmahmann, Jeremy D et al. (2016) Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis. J Neurophysiol 115:2280-5
Lewis, Richard F (2016) Vestibular implants studied in animal models: clinical and scientific implications. J Neurophysiol 116:2777-2788
Thompson, Lara A; Haburcakova, Csilla; Lewis, Richard F (2016) Vestibular ablation and a semicircular canal prosthesis affect postural stability during head turns. Exp Brain Res 234:3245-3257
Lewis, Richard F (2015) Advances in the diagnosis and treatment of vestibular disorders: psychophysics and prosthetics. J Neurosci 35:5089-96
Lewis, Richard F (2015) Vestibular Prostheses Investigated in Animal Models. ORL J Otorhinolaryngol Relat Spec 77:219-226