Monday, April 7, 2025
4/7/2025
Nonlinearities in Human Vestibular Reflexes - Project Summary/Abstract The long-term goal of our research program is to assess the natural disease state of age-related changes in the vestibular system and improve clinical diagnosis and rehabilitation efforts in adult patients with balance disor- ders. The overall objective of this application is to use novel electrophysiological methods to identify, for the first time in humans, nonlinearity in cervical and ocular vestibular evoked myogenic potentials (VEMPs) – these re- sponses reflect activation of the otolith balance organs that detect linear acceleration and are important for bal- ance function. Nonlinearities of the vestibular system are crucial to its normal function, but these nonlinearities remain unstudied in humans. The purpose of Aim 1 is to characterize nonlinear response properties and effects of aging on cervical VEMPs (cVEMPs), reflecting stimulation of the saccule. The purpose of Aim 2 is to charac- terize nonlinear response properties and effects of aging on ocular VEMPs (oVEMPs), reflecting stimulation of the utricle. Parallel experiments for each aim will use novel stimulation approaches that allow responses to sustained vestibular stimulation to be examined. It is hypothesized that stronger nonlinearities will be associated with better balance function and that a lack of nonlinearities will be associated with poorer balance function. It is further expected that nonlinear distortion products in these responses will be poorer in both middle age and older adults – earlier than what is observed with conventional, clinical VEMP measures - as reflected in measures of total harmonic distortion, consistent with a loss of nonlinear processing. Significant impacts of this research will include 1) the creation of an early-detection model of vestibular degradation in aging adults, and 2) the develop- ment of phenotypes, or profiles, of vestibular aging. To date, the largest barrier to clinical phenotyping vestibular dysfunction is lack of sensitive clinical tools, a barrier the results of this study will overcome. Once it is known how measurements of nonlinearity in the vestibular system change with age and affect functional balance, more sensitive measures of vestibular disease and interventions for risk of falls can be developed. From a basic science perspective, the proposed research will help define the biological process of aging on the processing of otolith organs and vestibular muscle reflexes – even in the case of unexpected findings with no age-related decrements observed, we will discover new knowledge regarding human vestibular function. From a clinical perspective, information gained from the proposed research plan will help to improve approaches to assessing the human balance system by using the data to identify aging phenotypes, thereby improving our understanding of both heterogeneity in the aging vestibular function and early detection of adults at risk of falls.
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