Spatial Orientation, Navigation, and Neuropsychologic Function in Patients With Vestibular Implant

Overview

The vestibular system, located in the inner ear, provides information to the brain information about how head acceleration and orientation relative to gravity. Damage to the vestibular system is usually permanent and can contribute to a lower quality of life. The goal of this research is to to examine how vestibular implants (VI) may improve performance of cognitive tasks in patients with severe vestibular damage. These higher-level cognitive behaviors include (1) orientation relative to gravity, (2) navigation, and (3) neuropsychologic function. VI patients will be tested in these three cognitive domains across study sessions: pre-stimulation (VI implanted but stimulation OFF), following chronic stimulation (12 days, VI-ON), and then again 1 month later with the VI turned off. There will be both "true" stimulation experiments during which the VI will provide motion-modulated stimulation and also "placebo" stimulation (no motion cues, tonic stimulus). The order of these experiments will be randomized and separated by 3 months. Researchers will compare VI data in the three cognitive domains (spatial orientation, navigation, \& neuropsychologic function) with control data from non-implanted bilateral vestibular loss (BVL) and unilateral vestibular loss (UVL) patients and normal subjects.

This project will test the capability of a vestibular implant (VI) to improve cognitive dysfunction in patients with severe vestibular damage. At Mass Eye and Ear (MEE), we will test non-implant vestibular patients with differing degrees of vestibular damage. At the University of Geneva (UNIGE), they will recruit and implant patients with severe vestibular and auditory deficits with a combined cochlear and vestibular implant. These are the patients with VIs we intend to test in collaboration with the UNIGE team. Notably, all implant surgeries are done at UNIGE as part of their ongoing vestibular implant research. The team at MEE submitting this CT.gov study is not involved with any aspect of the recruitment, surgery, or post-operative care of the patients receiving implants at UNIGE. We will work with the team at UNIGE to study these patients after they have received the VI on the protocols described below before, during, and after they receive stimulation from the VI. Specifically, we will measure how higher-level behaviors, including spatial orientation, navigation, and neuropsychologic function, are affected by stimulation provided by the vestibular implant, and in parallel will study these behaviors in non-implanted patients with different degrees of vestibular impairment. Our goal is to determine if the cognitive dysfunction experienced by patients with severe vestibular damage can be improved with prosthetic stimulation, findings which would expand the clinical utility of the vestibular implant while concomitantly improving understanding of the role of vestibular information in cognition. Damage to the vestibular periphery is typically permanent and untreatable (aside from physical therapy), and when it is bilateral, can result in severe degradation of vestibular-dependent behaviors. The VI was developed as a vestibular analogue to the widely employed cochlear implant, senses the head's angular velocity in three-dimensions, and provides this information to the brain by stimulating semicircular canal afferents using implanted electrodes. While VI research has progressed from animal models to human patients with vestibular damage, it has focused almost exclusively on eye movements and to a lesser extent balance and gait (although recent human studies also queried subjective measures of dizziness and quality of life). Cognitive processes have been ignored in prior VI studies, even though cognitive symptoms (often referred to as "brain fog") can be prominent and disabling in vestibular-deficient patients. More generally, vestibular contributions to cognition remain controversial and poorly characterized. In this study, we will investigate the effects of VI stimulation on (1) spatial orientation, (2) navigation, and (3) neuropsychologic function by characterizing these behaviors in patients with bilateral vestibular loss (BVL) who have unilateral VIs, with and without chronic vestibular stimulation. To serve as benchmarks for the BVL patients with/without VI stimulation, and to define the effects of vestibular loss on cognitive behavior, we will also study non-implanted BVL and unilateral vestibular loss (UVL) patients and normal subjects. Subjective assessments of cognitive function, dizziness and perceived disability will be also be measured using patient reported outcome measures (PROMs) and we will also assess more general quality-of-life metrics. We predict that the VI will improve spatial orientation, navigation, and visuo-spatial neuropsychologic function in BVL patients and that these measures will display correlations with the PROMs that characterize symptom severity and quality-of-life metrics. In sum, the proposed work will be the first to examine the capability of chronic VI stimulation to improve the cognitive deficits caused by severe vestibular damage, and will also examine the association between the severity of vestibular damage and the degree of cognitive deficits, and the relationship between vestibular-mediated cognitive deficits and the metrics that quantify subjective disability. This work will advance scientific knowledge while promoting the development of the VI as a therapy that has the potential to improve the clinical status and quality-of-life for vestibular-deficient patients.