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

> **NIH NIH R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2024 · $632,334

## Abstract

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...

## Key facts

- **NIH application ID:** 10803344
- **Project number:** 1R01AG075532-01A1
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Faisal Karmali
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $632,334
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803344

## Citation

> US National Institutes of Health, RePORTER application 10803344, Contribution of vestibular dysfunction and its central multisensory integration to imbalance in aging (1R01AG075532-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10803344. Licensed CC0.

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