Mark A. Segraves, Ph.D. - US grants

Description: The long-term goal of this laboratory is to understand the contributions made by the primate's cerebral cortex to the control of motor behavior. Current experiments are focused on the role of the rhesus monkey's frontal eye field (FEF) in the generation of eye movements. The FEF is a cortical region that is closely tied to sensorimotor processing. The FEF is found in both human and non-human primates and appears to be particularly important for eye movements that are driven by cognitive processes, for example, when a saccade is made to a remembered location or for the patterns o eye movements generated during reading or the examination of a complex visual scene. The FEF contains neurons whose firing is related to the generation of saccades, and projects to the superior colliculus as well as to other oculomotor regions of the brainstem. This project has three components designe to increase our understanding of FEF function in the generation of individual saccades, including contributions to initiation, velocity and amplitude, as well as in the planning of generation of complex sequences of saccades such as those used to survey a visual scene. In the first component, we will employ a behavioral paradigm developed in our laboratory to evoke natural scanning eye movements. In this paradigm, eye movements and neural activity can be recorded while a monkey freely views projected visual images. For the current project, we intend to examine this behavior before and after the injection of GABAergic drugs in the FEF. This manipulation will help to reveal FEF contributions to natural scanning eye movements either by the short-term removal of FEF input, with the inhibitory drug muscimol, or by making the FEF temporarily hyperactiv with the excitatory drug bicuculline. In the second component we will use the same microinjection techniques to examine the activity of saccade-related cell in the superior colliculus before and after the inhibition or excitation of FE input to the colliculus by microinjection. Comparing the resultant eye movemen behavior to changes in collicular cell activity will enhance our understanding of both the FEF and collicular contribution to the generation of these movements. In the third component, we will attempt to enhance our understandin of the functional organization of the FEF by using electrophysiological and anatomical techniques to generate a complete topographical map of the organization of saccade vectors in the FEF. This map will serve as an invaluable tool for future studies of the FEF. Because of known and expected similarities between rhesus monkey and human oculomotor cortex, these experiments will also provide a model for the functional organization of the cortical control of voluntary movement in humans.

DESCRIPTION (provided by applicant): The overall goal of these experiments is to understand how the brain controls where we look. To accomplish this, it is important to study brain activity and behavior under conditions that closely approximate those in the real world. All of the experiments we propose to do will use awake behaving rhesus monkeys as subjects. In prior work, we have studied activity in the cortical frontal eye field while monkeys looked at images of natural scenes. The frontal eye field (FEF) is closely involved in the control of purposive voluntary eye movements. While the monkey searched for a target hidden in the images of natural scenes, the activity of FEF neurons consisted of combinations of activity related to planning upcoming eye movements, as well as activity that was sensitive to salient visual features of the image. In parallel with the development of our understanding of how the brain controls eye movements, there have been substantial advances in our understanding of the features of natural images that guide both human and monkey eye movements. These behavioral studies are at the advanced level of being able to accurately predict patterns of eye movements. Our goal in this proposal is to take advantage of these advancements in predicting patterns of eye movements in natural environments to help us understand the brain events that are responsible for this behavior. We will focus upon neuron activity in the FEF due to its essential role in the control of voluntary eye movements. The proposal has 3 Aims each focused upon a different factor that is known to guide eye movements under natural conditions. Salience describes how different a small part of a visual scene is from the remainder of the scene based upon stimulus features such as color, contrast, shape, and orientation. Our first aim will define the effects that salience has upon FEF activity. In our second aim, we'll quantify the effects of relevance. Relevance refers to the importance of visual features for the task at hand; for example, if we're looking for a red target, the red items in the image will be more likely to attrat our attention and ultimately be the target for an eye movement. Knowing the broad composition of a scene, a quality that is called scene gist, can tell us the places where an object is more likely to be found. For example, if we are looking for a bicycle, we are more likely to search the sidewalks and roadways of a street scene and ignore other places where bicycles are unlikely to be found. Our final aim will look for the effects of scene gist upon monkey behavior and the FEF activity driving that behavior. In addition to the brain recording experiments outlined above, a large part of our effort will be devoted to mathematical analysis and modeling of the behavioral and neuronal data we obtain. Our ultimate goal is to provide a model that predicts the contributions of salience, relevance, and gist to the activity of FEF neurons. The successful model will be a mathematical representation that predicts search-related activity in the FEF for both artificial and real world conditions. PUBLIC HEALTH RELEVANCE: Due to the known and expected similarities between monkey and human eye movement systems, these experiments provide a model for the functional organization of frontal eye field cortex in humans. The ability to make appropriate eye movements is a function that can be damaged by a number of diseases, including cerebral stroke, Alzheimer's, Parkinson's, and Schizophrenia. More specifically, deficits in the proper control of fixation during search of complex visual stimuli have been described in patients suffering from simultanagnosia, as well as in individuals with a diagnosis of autism spectrum disorder.

DESCRIPTION (provided by applicant): The mammalian superior colliculus (SC) is a subcortical structure that integrates visual and other sensory information to initiate orienting movements of the eyes and head. A fundamental feature of SC organization is that the representations of sensory inputs and motor outputs are topographically arranged and aligned. While great progress has been made in understanding the development of the visual representation in the SC, how the motor maps are formed and aligned with the visual map remains unknown. In order to take advantage of the available genetic tools in mice, the investigators propose to perform a comprehensive investigation of the organization and development of motor maps in the mouse SC. First, electrical microstimulation will be conducted in the deep layers of the SC to evoke saccade-like rapid eye movements in mice. The topographic organization of the eye movement map will be revealed by systematically varying the stimulation sites in the SC and determining the amplitude and direction of the evoked movements. Single-unit recording will also be performed in the deep layers to determine how individual neurons encode eye movement direction and amplitude, and how such movement fields are mapped in the mouse SC. Second, the same experiments will be performed in mice deprived of visual experience from birth and in an existing transgenic mouse line that have altered visual maps in the SC. These experiments will determine whether visual inputs provide an instructive signal for motor map development and visuomotor alignment. Together, the proposed experiments will provide the first systematic mapping of the deep layers of the mouse SC and initiate studies on factors influencing sensorimotor development. These studies will have important implications for the understanding and potential treatment of human eye movement disorders and other diseases that result from miswiring of neuronal connections. 6