Subthreshold vestibular stimulation as a strategy for rehabilitation - 1 Project Summary/Abstract 2 In individuals with bilateral vestibular hypofunction (BVH), vestibular responses to self-motion cues are reduced 3 bilaterally, often without a defined cause. The persistent state of desensitization yields symptoms of bouncing or 4 unstable vision, dizziness, imbalance, and falls; collectively, these symptoms lead to a substantial reduction in 5 quality of life. However, despite the sizeable impact of BVH on quality of life, health care expenditures, and falls, 6 interventions tailored to the specific needs of patients with BVH, as opposed to patients with unilateral lesions, 7 have yet to be developed. The objective of this proposal is to investigate a novel strategy for improving vestibular 8 function in individuals with BVH. The nervous system possesses a robust capacity to regulate neural activity in 9 the face of changing environmental or internal conditions. When exposed to a weak sensory stimulus (e.g., slow 10 movements of the head), a specific type of neural plasticity, “homeostatic plasticity”, has been shown to increase 11 the responsiveness of the involved neurons to subsequent motion stimuli. In this project, we aim to determine if 12 such mechanisms, prompted by periods of subthreshold (i.e., low amplitude) motion, may serve as a potential 13 strategy for driving plasticity in the lesioned vestibular system. Specifically, in individuals diagnosed with BVH 14 we will (1) measure changes in sensitivity to self-motion cues immediately following a subthreshold motion 15 stimulus (Aim 1), (2) characterize changes in vestibular function after repeated exposure to a subthreshold 16 motion stimulus (Aim 2), and (3) determine if the addition of a subthreshold motion “primer” can improve the 17 outcomes of vestibulo-ocular reflex (VOR) adaptation (Aim 3A) and balance training (Aim 3B). We hypothesize 18 that the use of a subthreshold stimulus, secondary to its capacity to drive plastic changes in the vestibular 19 system, will lead to an increased sensitivity to self-motion cues, as well as positive changes in vestibular function 20 (e.g., gaze stability, balance), in patients with BVH. In accordance with the topic of the proposed research project, 21 my long-term career goal is to establish a research lab that focuses on developing innovative treatments for 22 vestibular dysfunction. To achieve this goal, the proposed career development plan focuses on acquiring the 23 skills and knowledge required to design, implement, monitor, and analyze the results of clinical trials in the 24 rehabilitation sciences; more specifically, this includes (1) gaining a better understanding of the 25 neurophysiological principles underlying vestibular plasticity/learning, (2) learning state-of-the-art techniques for 26 analyzing the behavior of the VOR, and (3) learning current methods for adapting the gain of the VOR. The 27 mentored phase of the training plan will take place at Ohio State University in the lab of Dr. Daniel Merfeld, PhD. 28 Consistent with the translational nature of the project, the mentorship team will consist of clinician-scientists and 29 basic vestibular scientists, both at Ohio State (Daniel Merfeld, PhD & Kevin Kerber, MD) and at external 30 institutions (Michael Schubert, PT, PhD, and Soroush Sadeghi Ghandehari, MD, PhD). 31 32 33 34 35