PROJECT SUMMARY Loss of vestibular function causes visuospatial misperception, imbalance, and decreased visual acuity during head motion, leading to severe impairment of daily activities. Vestibular rehabilitation therapy is the standard of care for treating these associated symptoms, but it is not universally effective and there are no objective means for identifying mechanisms that contribute to the recovery when it is successful. Following loss of vestibular function, each patient may have a distinct predisposition toward relying on one or another sensory modality (e.g., vision or somatosensory inputs), or may adopt a different strategy to cope with the aberrant vestibular information (e.g., blink during head rotation). These intricate responses can result in different patterns of sensorimotor reorganization during recovery. Another major constraint rerated to vestibular recovery is the lack of objective assessments of otolith and semicircular canal function, as the current outcome measures instead rely on the clinician judgment. Such lack of quantitative measures of the vestibulo-ocular reflex (VOR) and other sensory substitutions preclude the ability to predict functional outcomes and identify those patients who could benefit most from rehabilitation. To address this issue, the objective of this project is to examine whether novel video- oculography (VOG) measures of the VOR can be used as valid markers of functional outcome following vestibular loss. To this end, we will use the video head impulse test (vHIT) to measure semicircular canal function. For assessment of the otolith function, we have developed a VOG method based on ocular counter-roll (vOCR), during which the torsional VOR is quantified with lateral head tilt. Our preliminary results show recovery in vOCR with vestibular compensation over time, whereas the VOR gain as measured by vHIT remains abnormal in all stages of recovery following vestibular loss. Some patients however generate compensatory saccades that conceal their VOR deficit, suggesting a saccade strategy that may be related to the adequacy of vestibular compensation. In addition, we have found that the difference in vOCR during en bloc head-and-body tilt versus head-only tilt can be used as a measure of sensory substitution for vestibular loss during recovery. Based on these findings, our central hypothesis is that vOCR with whole- body/head-only tilt and compensatory saccades with vHIT can be used as novel markers to (i) measure recovery and (ii) predict functional outcomes following vestibular loss. We expect that the findings in this project will also provide the basis for a future grant that investigates customized vestibular rehabilitation using discrete and easy- to-apply VOG measurements in individual patients rather than applying a fixed treatment protocol in all patients.