This research program is motivated by two interrelated goals. First, we seek to understand the neural mechanisms by which the brain recovers after loss of vestibular (inner ear balance) sensation on one or both sides. Second, we seek to advance development new treatment approaches to maximize quality of life for individuals disabled by disequilibrium and unsteady vision after loss of vestibular sensation. In the United States alone, about 150,000 people suffer disabling vertigo and unsteadiness each year due to acute unilateral loss of vestibular function, while about 250,000 suffer chronic imbalance and unsteady vision typical of severe bilateral loss that fails to resolve despite existing treatments. Sudden, permanent loss of vestibular nerve input from one labyrinth causes disequilibrium and visual blurring due to disruption of the vestibulo-ocular reflex (VOR), which normally maintains stable vision during head movements. This disruption is usually followed by impressive but incomplete recovery. During the previous funding period, we made excellent progress toward defining the dynamics of VOR compensation and the neural mechanisms upon which it depends. In the proposed research program, we will build upon this solid foundation of progress through three interrelated and synergistic aims. Experiments addressing Aim 1 will characterize the role of floccular target neurons [FTN] during VOR compensation after acute unilateral injury, examining dynamic changes in their sensitivity to vestibular, proprioceptive and efference copy signals. We predict that compensation involves a coordinated sequence of adaptive changes in two largely parallel paths (i.e., FTN and position-vestibular-pause [PVP] neurons), because our recent results show that changes in PVP neurons alone are insufficient to explain VOR recovery.
Aim 2 is to characterize and optimize the pattern of vestibular nerve activity engendered by a multichannel vestibular prosthesis (MVP) we recently created to restore balance sensation to individuals disabled by loss of inner ear function. These experiments are essential for optimizing MVP performance prior to the start of a clinical trial. Finally, studies in Aim 3 will merge the approaches used in Aims 1 &2, using the MVP to realize a previously impossible experimental paradigm that will characterize and correlate central vestibular neuron responses and VOR responses during both loss and restoration of sensory input from the vestibular labyrinth. Combined, these studies will (1) enhance our understanding of how the central nervous system adapts after initially disabling injuries;(2) advance development of a potentially revolutionary tool for replacement of labyrinthine sensation;and (3) clarify how neuronal mechanisms thought to underlie learning at a cellular level can be leveraged to optimize recovery of complex behaviors like the VOR in alert animals and, ultimately, in individuals disabled by loss of vestibular sensation.
After complete loss of vestibular (inner ear balance) sensation on one or both sides, most patients ultimately recover enough to do well, but some fail to compensate and remain disabled by chronic imbalance and inability to see clearly while moving. This research project will define neural mechanisms that underlie how the brain compensates after vestibular injury and advance development of an implantable bionic inner ear device that can replace lost vestibular sensation.
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|Brooks, Jessica X; Cullen, Kathleen E (2014) Early vestibular processing does not discriminate active from passive self-motion if there is a discrepancy between predicted and actual proprioceptive feedback. J Neurophysiol 111:2465-78|
|Oman, Charles M; Cullen, Kathleen E (2014) Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology. Exp Brain Res 232:2483-92|
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|Mitchell, Diana E; Dai, Chenkai; Rahman, Mehdi A et al. (2013) Head movements evoked in alert rhesus monkey by vestibular prosthesis stimulation: implications for postural and gaze stabilization. PLoS One 8:e78767|
|Ward, Bryan K; Agrawal, Yuri; Hoffman, Howard J et al. (2013) Prevalence and impact of bilateral vestibular hypofunction: results from the 2008 US National Health Interview Survey. JAMA Otolaryngol Head Neck Surg 139:803-10|
|Dai, Chenkai; Fridman, Gene Y; Chiang, Bryce et al. (2013) Directional plasticity rapidly improves 3D vestibulo-ocular reflex alignment in monkeys using a multichannel vestibular prosthesis. J Assoc Res Otolaryngol 14:863-77|
|Rine, Rosemarie M; Schubert, Michael C; Whitney, Susan L et al. (2013) Vestibular function assessment using the NIH Toolbox. Neurology 80:S25-31|
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