Contribution of vestibular dysfunction and its central multisensory integration to imbalance in aging

Project Summary The primary contributors to age-related imbalance remain poorly understood because nearly all contributors to balance deteriorate with age, including sensory inputs, central processing, motor outputs, biomechanics, cardiovascular function, and cognition. This proposal examines the contributions of age-related sensory

dysfunction and changes in central sensory processing to imbalance and falls. While vestibular, visual, and somatosensory contributions to imbalance will be broadly studied, vestibular (head motion and orientation cues) contributions are emphasized because these potentially important mechanisms have often been

overlooked. This topic is timely because new therapeutics (vestibular prosthetics, hair cell regeneration, non- invasive brain stimulation) are moving into clinical trials, so knowledge resulting from our project will provide a foundation for the long-term goal of mitigating fall risk by assigning patients to targeted interventions. While this

project is focused on understanding imbalance in older adults, it will also advance knowledge about the general neural principles underlying balance. Two specific aims will be studied: Aim 1) Investigate the contributions of vestibular, somatosensory, and visual dysfunction to imbalance in older adults and those with a

history of falls; and Aim 2) Investigate how standing balance is impacted by deficits in central sensory processing and closed-loop control in older adults. To investigate these aims, a large cohort of older adults, including those with a history of falls associated with loss of balance, will be studied using several synergistic

methods, including sensory (vestibular, visual, somatosensory) and non-sensory (muscle strength, cardiac and cognitive function) assays and quantitative measures of posture, gait, and falls. A sensitive threshold test will be used to quantify each individual’s sensory function on a continuum (rather than a binary classification) and

can be applied across sensory modalities using consistent physical units, offering a major advantage over other experimental approaches. Deficits in central sensory integration will be studied using closed-loop computational models applied to experimental data. A template for the effects of vestibular damage on

imbalance will be developed by testing young adults with peripheral vestibular damage who are otherwise healthy, allowing imbalance to be partitioned into that arising from vestibular dysfunction vs. other non- vestibular age-related sensory decline. The proposed research is innovative, in the applicant’s opinion,

because it: 1) determines how imbalance depends on the continuum of vestibular, visual and somatosensory function – a personalized, holistic understanding of imbalance; 2) develops strategies to study dysfunction in central sensory integration that will determine if the brain is correctly weighting sensory information based on

the quality of each sensory cue; and 3) advances a theoretical framework in which sensory measures and imbalance are related to neural noise/variability. These studies will help elucidate how sensory dysfunction and central integration contribute to imbalance in older adults, toward the long-term goal of mitigating fall risk.