Vestibular dysfunction due to ototoxic hair cell injury is a common cause of significant disability due to disequilibrium and inability to stabilize gaze during head movements. Although some patients with bilateral vestibular dysfunction are able to compensate through physical rehabilitation and reliance on other senses, those who fail to compensate currently have no good therapeutic options. Because the vestibular nerve should be intact in these patients, selectively applied electrical currents should be able to drive the nerve and elicit eye movements that can stabilize gaze. ? The central goal of this project is to further development toward an implantable neuroelectronic prosthesis capable of restoring vestibular function to people with symptomatic bilateral vestibular dysfunction. Although vestibular prosthesis development has lagged that of cochlear implants, one group has recently described a first prototype vestibular prosthesis. However, the eye movements it evoked were insufficient to stabilize gaze during natural head movements, and the experiments were performed on animals with normal vestibular function. It is unclear whether their results generalize to the case of a labyrinth damaged by ototoxicity or Meniere's disease. ? The proposed project will establish a physiologic and morphologic basis for vestibular prosthesis development, by refining a mammalian model of vestibular ototoxicity and by testing the biologic premises upon which prosthesis design is based. Because viable vestibular nerve afferents must exist for a prosthesis to stimulate, we will determine the effects of gentamicin toxicity on morphology and physiology of afferent fibers in semicircular canal crista. We will characterize the vestibulo-ocular reflex before and after bilateral treatment with ototoxic doses of intratympanic gentamicin. We will characterize the eye movements of bilaterally vestibular-deficient animals in response to single- and multi-canal patterned electrical stimulation of the semicircular canal cristae. We will test whether stimulation of canals in a single labyrinth can be combined to drive eye movements that cover the normal physiologic range. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DC006216-03
Application #
6887377
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
3
Fiscal Year
2005
Total Cost
$200,286
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Dai, Chenkai; Fridman, Gene Y; Chiang, Bryce et al. (2011) Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis. Exp Brain Res 210:595-606
Dai, Chenkai; Fridman, Gene Y; Davidovics, Natan S et al. (2011) Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel vestibular prosthesis. Hear Res 281:74-83
Rahman, Mehdi A; Dai, Chenkai; Fridman, Gene Y et al. (2011) Restoring the 3D vestibulo-ocular reflex via electrical stimulation: the Johns Hopkins multichannel vestibular prosthesis project. Conf Proc IEEE Eng Med Biol Soc 2011:3142-5
Hayden, Russell; Sawyer, Stacia; Frey, Eric et al. (2011) Virtual labyrinth model of vestibular afferent excitation via implanted electrodes: validation and application to design of a multichannel vestibular prosthesis. Exp Brain Res 210:623-40
Chiang, Bryce; Fridman, Gene Y; Dai, Chenkai et al. (2011) Design and performance of a multichannel vestibular prosthesis that restores semicircular canal sensation in rhesus monkey. IEEE Trans Neural Syst Rehabil Eng 19:588-98
Migliaccio, Americo A; Meierhofer, Robert; Della Santina, Charles C (2011) Characterization of the 3D angular vestibulo-ocular reflex in C57BL6 mice. Exp Brain Res 210:489-501
Della Santina, Charles C; Migliaccio, Americo A; Hayden, Russell et al. (2010) Current and future management of bilateral loss of vestibular sensation - an update on the Johns Hopkins Multichannel Vestibular Prosthesis Project. Cochlear Implants Int 11 Suppl 2:2-11
Migliaccio, Americo A; Minor, Lloyd B; Della Santina, Charles C (2010) Adaptation of the vestibulo-ocular reflex for forward-eyed foveate vision. J Physiol 588:3855-67
Fridman, Gene Y; Davidovics, Natan S; Dai, Chenkai et al. (2010) Vestibulo-ocular reflex responses to a multichannel vestibular prosthesis incorporating a 3D coordinate transformation for correction of misalignment. J Assoc Res Otolaryngol 11:367-81
Tang, Shan; Melvin, Thuy-Anh N; Della Santina, Charles C (2009) Effects of semicircular canal electrode implantation on hearing in chinchillas. Acta Otolaryngol 129:481-6

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