Stephen Heinen - US grants

This is a Shannon Award providing partial support for research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. Further scientific data for the CRISP System are unavailable at this time.

DESCRIPTION (adapted from application abstract): The smooth pursuit eye movement system is an exemplar of smooth motor control that relies on visual motion processing. Two relatively simple, yet powerful, models have been developed and both adequately describe many characteristics of the smooth pursuit response. The internal structures of the models are very different, and lead to different predictions for a wide variety of stimuli. Adapting procedures and stimuli from the domain of visual psychophysics, we propose experiments that test different components within the smooth pursuit models. Our experiments will also provide data on how the smooth pursuit system responds to stimuli with complex spatial and temporal characteristics. Our approach may also allow us to determine the extent that sensory motion processing limits the initial response of the smooth pursuit system and assess if common stages of motion processing underlying oculomotor and psychophysical performance. We propose to answer the following questions: 1) How precise is the pursuit system, and what limits its precision? 2) How does the pursuit system respond to directional signals? 3) What is the response of the pursuit system to acceleration? 4) What are the effects of backgrounds on smooth pursuit initiation? The results of the proposed experiments should guide further refinements of the current models of smooth pursuit. Experimental results on normal subjects may also provide fresh insights into subtleties of smooth pursuit and aid in the diagnosis of brain dysfunction that affects oculomotor control. The results may benefit strabismics, amblyopes and other individuals suffering from oculomotor pathology.

To maintain clear vision of an object at the fovea, the eyes must be moved to that object. Rapid eye movements, or saccades are used to acquire stationary objects, while smooth pursuit is used to stabilize moving objects. When an object remains stationary, high-resolution information is lost for only about 180 msec, the time required to generate a saccade. However, if an object is moving, the smooth pursuit system could never acquire that object because of this delay if it merely responded to retinal image motion. To solve this problem, the pursuit system uses past experience with tracking a familiar object trajectory and makes computations on ongoing motion to predict the future position of a moving target. Based on this neural computation, the eyes pursue the target at the appropriate time and with the appropriate speed. The substrate for predictive eye movements is not known. The dorsomedial frontal cortex (DMFC) participates in planning and other higher-order motor behavior. The principal investigator has preliminary evidence that this area may participate in planning and execution of smooth pursuit eye movements. The goal of this project is to study this area with electrophysiological techniques to understand how predictive neuronal coding of upcoming target motion is interfaced with the command to move the eyes. Specific aims are to answer the following questions: 1. Is the effect of internal planning on visually-guided pursuit multiplicative, or implemented by a switch? Neuronal activity recorded while the animal pursues a target (motor) will be compared with activity recorded while the target moves, but the animal continues to fixate (planning). 2. Does neuronal activity in the DMFC time fixation duration? We will pit an artificial timing signal against the signal in the DMFC by injecting small currents before an eye movement with durations that are different from the actual fixation period. 3. Does activity in the DMFC increase pursuit gain as a result of a release from inhibition? We propose to employ the GABAergic agents muscimol, which has an inhibitory effect on cortical function, and bicuculline, which produces a disinhibition of cortical cells to explore the balance between inhibitory and excitatory connections in the DMFC necessary to time pursuit initiation. 4. Does the smooth pursuit system use ongoing motion information to compute the trajectory of a target and thereby optimize initiation and perseveration of pursuit? We will monitor eye movements and single-neuron activity in the presence of targets that change curvature or speed in a fashion that would make a simple response to the motion inefficient.

DESCRIPTION (provided by applicant): Smooth pursuit is a voluntary eye movement that is used to view objects as they move. Although physiologists have studied many aspects of voluntary saccade control, most work on the neural control of pursuit has treated this system as if it responds reflexively to retinal-image motion. The pursuit system of primates is a sophisticated ocular movement system that has evolved to allow it to predict when and where an object will move, and to decide whether or not to pursue that object. The focus of the current grant period is to understand how the cortical eye fields cooperate to control voluntary smooth pursuit eye movements. Aims are to: 1. Compare the strength of predictive and retinal-image signals used by the cortical eye fields to execute a pursuit eye movement 2. Determine how the cortical eye fields interact to cancel a pursuit movement. 3. Determine how the decision is made to execute or cancel a pursuit movement. The results of these experiments should contribute to our knowledge of how the cortex moves the eyes to effectively view moving objects in the natural scene. The results of this work should provide basic data to facilitate diagnosis and treatment of disorders of vision such as strabismus and amblyopia, and to develop prosthetic devices to aid people who suffer from these disorders.

DESCRIPTION (provided by applicant): Most research on the smooth pursuit system has been conducted using a single spot target moving in isolation. This approach has been productive, and has resulted in elegant models that are consistent with the physiology of the motor limb of this system. However, in a natural scene many objects can move, each of which can have spatial structure and features that stimulate multiple motion detectors. Prevailing models do not describe how spatially distributed motion signals are processed to provide the driving signal for smooth pursuit. The long-term goal of this project is to determine how visual motion information is used to guide voluntary smooth eye movements in natural scenes, and to understand how eye movement systems cooperate when tracking complex moving targets with many articulated components. Our proposal addresses these issues using methodology and insight borrowed from the fields of visual psychophysics and oculomotor physiology to provide a complementary, collaborative approach to this problem. Specific aims are to: Determine the spatial organization of units that process visual motion for smooth pursuit. Determine if common motion processing limits smooth pursuit and perception of two objects. Determine signals affecting pursuit and saccadic performance while following a moving object and inspecting its features. The results should be applicable to the characterization of parameters of normal vision, and to the diagnosis and treatment of disorders of vision, strabismus and dynamic eye movement control.

Project Summary Smooth pursuit is usually studied with small, spot stimuli, yet extended natural objects stimulate peripheral retina and have features of interest. It is unknown how peripheral motion interacts with pursuit, or how attention is allocated to features during it. We have evidence that peripheral motion improves pursuit by minimizing saccades, and that attention is not locked to the fovea, but can be allocated flexibly to the periphery when the foveal pursuit burden is reduced. Furthermore, pilot data show that merely diverting attention from the fovea improves pursuit. It follows that a motion system incorporating peripheral retina can drive ocular pursuit more smoothly and allow an attentive process to simultaneously monitor local motion features, and our pilot data support this hypothesis. In addition we find that attentional resources for these pursuit and feature monitoring systems appear to be separate. Specific Aims are: Aim 1) Is attention allocation during pursuit flexible? Experiments will assess attention allocation under conditions that manipulate foveal attention demands while controlling for low-level features such as luminance transients. Aim 2) Does foveal attention increase saccades during pursuit? Experiments in this aim measure pursuit and manipulate attention and the locus of retinal stimulation. Aim 3) Do multi-element stimuli simultaneously support independent eye and attention movements? Experiments investigate whether attentional resources for pursuit and feature tracking are independent using attention operating characteristic (AOC) analysis. Other experiments will determine if only the attended elements are pursued, and if they are, if attention still arises from two sources.