MEMRI as an in vivo marker for changes in neuronal activity in central vestibular pathways

Vestibular organs transmit key information to central vestibular nuclei that control body position and movement in space as well as posture. Exposure to loud noise can result in dizziness, imbalance, and poor postural control, symptoms which suggest damage to the vestibular system. Military personnel, who are usually exposed to loud noise during training and while in theater, are more likely to experience these symptoms. Often symptoms dissipate and the system appears to be repaired. However, the subtle effect of noise damage may be cumulative and go unnoticed until the system is challenged, or symptoms manifest later in life when unsteady gait, imbalance, and poor posture become prominent. This puts our Veterans at higher risk for falls as they age. Falls account for more than 50% of accidental deaths. Current tests of otolith function are largely indirect and measures of central vestibular dysfunction are understudied. Identifying, understanding, and testing interventions for vestibular dysfunction in humans and in pre-clinical models requires central assessment tools, which are currently lacking in the field. The current studies will examine noise effects on central pathways while validating tools for future assessment of chronic effects. The goal is to provide a basis for future studies that will explore longitudinal changes centrally and correlate those changes with behavioral deficits. We propose to examine the impact of noise on the relationship between peripheral stimulation and central activity in central brain regions. First, we will compare patterns of activation centrally after stimulation of otolith vs canal using in vitro and in vivo markers of neuronal activity (Specific Aim 1). In Specific Aim 2, we will use these markers of neuronal activity to assess activity in central vestibular pathways following the same stimulation delivered in Specific Aim 1 at two time points after noise exposure. Functional and histological changes will also be assessed.