Faisal Karmali - US grants

DESCRIPTION (provided by applicant): Precision in motion control and perception is critical to survival - whether prey running over rough terrain or a pilot landing on an aircraft carrier. Behavioral precision depends on precision at many levels - e.g. sensory transduction, motor units, and the central nervous system - and there are open questions about which level(s) limit overall precision. As fundamental examples, we don't know whether the majority of vestibuloocular reflex (VOR) imprecision originates in the periphery, the CNS, or the oculomotor system. Similarly, we do not know whether the majority of perceptual imprecision originates in the periphery or CNS. The long-term general goal of this research is to understand the role of precision in sensation, behavior, pathology, clinical diagnosis and neural processing. The relative simplicity of the vestibular system makes it an excellent model to study the basic principles of how the brain processes noise, which may be more broadly applicable to other sensory systems. The short-term goal of this work is to understand precision in vestibular sensorimotor reflexes and perception using novel techniques to measure and isolate sources of imprecision. For example, the sensitivity of clinical tests at diagnosing particular disorders coul be strengthened if sources of imprecision could be isolated. To achieve this goal, we propose the following specific aims. Aim 1: Study sensory, motor and perceptual noise by simultaneously assaying VOR and perceptual precision in humans. To determine the extent to which the VOR and perceptual thresholds depend on a shared noise source, we propose to measure perceptual and VOR responses simultaneously using threshold-level stimuli, and quantify trial-by-trial co-variation. We hypothesize that a shared, presumably peripheral sensory noise source underlies both perceptual and oculomotor responses for yaw rotation and inter-aural translation. Aim 2: We will separate sensory and motor precision by exploiting a unique characteristic of the translational VOR - that the sensitivity of the response can be modulated by fixation distance - allowing the effective decoupling of the sensory and motor components of the pathway. We will measure trial-to-trial VOR variability in response to repeated stimuli, while presuming that VOR variability dependent on sensory imprecision will scale with VOR sensitivity. We hypothesize that sensory noise dominates translational VOR variability.

The goal of this proposal is to investigate vestibular precision by quantifying the variability in behavioral responses that result from the neural noise inherent to the peripheral and central vestibular systems. Because neural noise contaminates the signals that are transduced by the ear and processed by the brain, vestibular- mediated behavioral responses vary even when identical stimuli are provided. In this proposal, we focus on vestibular precision in human subjects and investigate its sources, its effects on behavior, and its degradation when the periphery is damaged and its potential plasticity. Specifically, we will investigate: SA 1: Vestibular precision in normal subjects ? physiology: A) We will measure the angular and linear vestibulo-ocular reflex (VOR) using novel motion combinations that reinforce or cancel eye movement responses, which will allow us to determine the distribution and magnitude of noise produced in the sensory (canal, otolith) pathways and in the oculomotor pathway. We hypothesize that normal subjects will demonstrate a bimodal distribution of noise with either sensory or motor predominance, and that subjects with more sensory noise will demonstrate other behavioral characteristics that reflect this characteristic (e.g., higher perceptual thresholds); and B) We will assay vestibular noise from trial-trial variations in the VOR and will compare VOR dynamics with those predicted by a Bayesian model using the assayed noise. We predict variations in VOR dynamics across subjects, age and stimulus amplitudes will be consistent with Bayesian processing of noise. Potential confounding factors will be carefully controlled, including attention, fatigue, and non-vestibular cues. SA 2: Vestibular precision after peripheral damage ? pathophysiology: A) We will examine the changes in vestibular precision that occur when one vestibular nerve is damaged (by a vestibular schwannoma, VS) and after the damaged nerve is surgically sectioned, and will investigate if precision measurements can provide evidence of pathologic noise produced by the damaged nerve and therefore help predict clinical outcome when the nerve is sectioned. We hypothesize that changes in signal reliability due to the VS will be traceable to both the reduced redundancy caused by loss of afferent fibers and to aberrant noise generated by the damaged vestibular nerve and that changes in precision after neurectomy will correlate the outcome measures that characterize patient disability; and B) We will examine the plasticity of vestibular precision in the oculomotor and perceptual realms with the goal of determining if precision can be improved. Using novel training approaches that provide challenging signal extraction tasks, we hypothesize that subjects will improve their vestibular precision on the trained task. As secondary outcome measures, we will determine if training one behavior generalizes to the non-trained behavior and if patient?s symptoms are affected by improved precision.