Peter H. Schiller - US grants

Several parallel channel and feedback loops have been identified in the mammalian visual and oculomotor systems. In order to better understand the dynamics of interactive information processing implied by such circuitry, our approach is to selectively and reversibly disrupt various input channels and feedback loops while we examine either the visual capacities of animals or the activity of single cells in visual and oculomotor structures. The work will be carried out on alert, trained animals involving mostly rhesus monkeys. We will examine (1) how the ON/OFF and the color-opponent/broad-band systems originating in the retina contribute to vision and visually guided eye movement, (2) how the responses of single cells to behaviorally relevant and irrelevant stimuli are influenced by various channels and feedback loops in the lateral geniculate nucleus and the visual cortex (V1-V4), and (3) how the frontal eye fields, the superior colliculi and inputs to these two structures interact to produce visually guided eye movements.

Five years of renewed support is requested for three core facilities in the Department of Brain and Cognitive Sciences at MIT. Since the original core award in 1983, several significant departmental changes have occurred. The Psychology Department has been reorganized and renamed the Department of Brain and Cognitive Sciences, and Dr. Emilio Bizzi has become its new chairman. A substantial portion of the research and core facilities of the department have been moved into a new building (Whitaker College) and several new appointments have been made. Consequently the graduate program has been enlarged and the number of graduate students has been increased. In this core grant we now list 14 investigators, 8 of whom are supported by Eye Institute grants. Research in vision includes the following fields: (1) neurophysiological studies of the visual and oculomotor systems; (2) anatomical studies of the visual pathways; (3) development of vision and visuomotor function; (4) human and animal psychophysical studies of visual function; (5) neuropsychological studies of visual capacities in normals and in pathological patients; (6) computational models of vision; and (7) neurotransmitter studies of retinal function. We are now seeking continued funding for our electronic and instrument shop modules, which form an essential part of our efforts. Because of our expanded clinically related work and the need for more extensive statistical analysis in other areas, we are requesting a new module for biostatistical analysis.

The cortical control of visually guided saccadic eye movements involves of two major systems, the anterior and the posterior. The anterior system, comprised of the frontal eye fields (FEF) and the dorsomedial frontal cortex (DMFC), has direct access to brainstem oculomotor centers. The posterior system, comprised of several regions of the occipital and parietal cortices, does not appear to have direct access to the brainstem; for the most part it reaches these centers either through the superior colliculus or through the frontal lobe. The major focus of the proposed work is to understand the manner in which these two cortical systems control visually guided eye movements, how they differ from each other and how they interconnect. Behaving rhesus monkeys will be studied using recording, electrical microstimulation, reversible inactivation, and lesion methods. Part of the work will utilize chronic multiple single-cell recordings that will enable us to study neuronal properties over extended time periods to study organizational changes in individual neurons. We have devised an extensive battery of tests, some of them new, to study the visual and visuo-motor capacities of animals. One of these tests that utilizes dual targets presented with various temporal asynchronies. will be used to study the extinction phenomenon both in monkeys and patients with brain damage to the anterior and posterior eye-movement systems. The proposed research will increase our knowledge of the neural control of eye and limb movements and will allow us to compare these systems in monkeys and humans.

Information is processed along several parallel channels in the primate visual system. Some of these channels have been amply characterized with physiological and anatomical methods. In spite of this, at present we have only limited knowledge of the functions of these channels and why they have emerged in the course of evolution. The purpose of the proposed work is to obtain new evidence as to the function of two sets of channels in the visual system, the ON and OFF channels and the color-opponent and broad- band channels. To accomplish our aim, we have developed methods which allow us to reversibly or permanently inactivate some of these channels at various levels in the visual system using either pharmacological agents or lesions. Employing a combination of physiological and psychophysical methods we can then proceed to determine the neural responses and the visual capacities of monkeys while their visual system is intact or while one of the channels is blocked. The physiological methods we use are the electroretinogram and single-unit recordings in various parts of the visual system. The psychophysical methods we use involve training animals on a variety of detection and discrimination tasks allowing us to obtain reliable measures of the following visual capacities: color and luminance contrast sensitivities, stereopsis, acuity, pattern perception, motion perception and flicker sensitivity. Central to this effort is our ability to obtain psychophysical functions for specific retinal locations which we believe is an essential requirement for this kind of work. The findings of this research on the neural mechanisms of vision should provide significant new hints about the nature, cause and locus of visual deficits in patients, especially as it pertains to binocular vision where defects are most common in our society.

Five years of renewed support are requested for three core facilities in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology. Ours is a growing department which at present has 14 investigators who carry out research on vision, the visual system and the oculomotor system. We are in the process of making additional appointments in these areas. We have 10 grants from the National Eye Institute. The research carried out by the 14 investigators of the Core Group includes the following areas of research: (1) neurophysiological studies of the visual and oculomotor systems, (2) anatomical studies of the visual and oculomotor systems, (3) developmental studies of the vision and visuomotor function, (4) psychophysical studies of visual functions in non-human primates, (5) psychophysical studies of visual functions in normal human and patient populations, (6) computational analyses of vision and eye movement and (7) molecular and genetic studies of visual system formation. The three facilities supported by the Core Grant, the Instrument Shop, the Electronics Shop and the Biostatistical Module are in extensive use by the Core Group. During the past four years these investigators have been most productive and have published more than 200 papers. The Core Facilities have made a highly significant contribution to the overall research efforts of this group and have fostered interaction among investigators involved in vision and visuomotor research. Continued support of the Core Facilities will be of great benefit to our future investigations.

vision; biomedical equipment resource; biomedical facility;

Five years of renewed support are requested for two core facilities in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology. Ours is a growing department which at present has 13 investigators who carry out research on vision, the visual system and the oculomotor system. We are planning to make additional appointments in these areas. We have 9 grants from the National Eye Institute. The research carried out by the 13 investigators of the Core Group includes the following areas of research: (1) neurophysiological studies of the visual and oculomotor systems, (2) anatomical studies of the visual and oculomotor systems, (3) developmental studies of the vision and visumotor function, (4) psychophysical studies of visual functions in non-human primates, (5) psychophysical studies of visual functions in normal human and patient populations, and (6) computational analyses of vision and eye movement. The two facilities supported by the Core Grant, the Instrument Shop and the Electronics Shop, are in extensive use by the Core Group. During the past four years these investigators have been very productive and have published numerous papers. The Core Facilities have made significant contributions to the overall research efforts of this group and have fostered interaction among investigators involved in vision and visumotor research. Continued support of the Core Facilities will be of great benefit to our future investigations.

The focus of our research for the next five years will be to determine the functions of extrastriate visual cortical areas and how the neurons therein perform coding operations. Our ongoing work on rhesus monkeys suggests that extrastriate cortical areas did not evolve, as had been previously suggested, to separately analyze different basic aspects of vision such as color, depth, motion, form, and texture. Instead, many more extrastriate areas engage in higher-level analyses than had been thought. These areas co-process several visual attributes and have, in part, evolved to facilitate object recognition in three dimensional space and to recognize objects when they are partially occluded or are seen from different perspectives under various conditions of illumination. The ability to learn and store visual objects in memory is an essential part of this process. To test these hypotheses we plan to apply three kinds of experimental procedures in our research: (1) recordings with single and multiple electrodes to assess the response properties of neurons in extrastriate areas using three dimensional stimuli that are transformed in various ways, (2) chronic recordings with implanted electrode arrays to determine how the response properties of cells are altered during the process of learning new visual objects, and (3) assessment of the visual capacities of animals on a broad range of tests after the removal of selected extrastriate cortical areas. The proposed work has important clinical relevance as it will serve characterize the functions of various visual cortical areas.

[unreadable] DESCRIPTION (provided by applicant): Five years of renewed support are requested for two core facilities in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology. Ours is a growing department which at present has 13 investigators who carry out research on vision, the visual system and the oculomotor system. Due to major support from the McGovern family and the Picower Foundation, two major new centers have been formed at MIT (the McGovern Institute for Brain Research and the Picower Center for Learning and Memory) in which numerous new appointments will be made the next five years, with several of them in vision and oculomotor control. Some of these appointments have already been made. Presently we have 12 grants from the National Eye Institute. The research carried out by the 13 investigators of the Core Group includes the following areas of research: (1) neurophysiological studies of the visual and oculomotor systems, (2) anatomical studies of the visual and oculomotor systems, (3) developmental studies of the vision and visuomotor function, (4) psychophysical studies of visual functions in non-human primates, (5) psychophysical studies of visual functions in normal human and patient populations, and (6) computational analyses of vision and eye movement. The two facilities supported by the Core Grant, the Instrument Shop and the Electronics Shop, are in extensive use by the Core Group. During the past four years these investigators have been very productive and have published extensively as documented in this application. The Core Facilities have made significant contributions to the overall research efforts of this group and have fostered interaction among investigators involved in vision and visuomotor research. Continued support of the Core Facilities will be of great benefit to our future investigations. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This is a revised application that has taken into account the comments of the referees who have evaluated the initial submission of the grant. In a separate section, a point-by-point response is made to the criticisms. The Preliminary Studies section has been expanded to include a series of pilot experiments we had carried out the past six months that deal with the central criticisms advanced by the referees and provide evidence that the projects proposed are feasible and are likely to lead to significant new understanding of the role areas V1 and V2 play in target selection with visually guided eye movements. This grant application replaces EY00676 entitled Parallel information processing in the visual system that we decided not to renew because the work under that grant has been largely completed and because the new discoveries we had made dictate a shift in our effort. The aim of the proposed research is to determine what role areas V1 and V2 of the primate play in the selection of visual targets with saccadic eye movements. Rhesus monkeys will be trained on a variety of behavioral tasks to enable us to study their visual capacities and their ability to select visual targets with saccadic eye movements. Single-cell recordings, microstimulation, and the application of GABAergic neurotransmitter agonists and antagonists will be used to assess how areas V1 and V2 interact and how they contribute to the generation of saccadic eye movements to visual targets. The proposal is based on a recent set of findings from our laboratory that has established that these two areas are centrally involved in target selection with visually guided saccadic eye movements. The work has shown that electrical stimulation of the infragranular layers of V1 and V2 enhances the generation of saccadic eye movements to visual targets at very low current levels whereas stimulation of the supragranular layers interferes with target selection. In addition to clarifying the role of V1 and V2 in the generation of visually guided saccadic eye movements, the proposed research should have significant bearing on microstimulation prosthetics for the visually disadvantaged as it will specify the effects of microstimulation of different layers of the visual cortex and what roles various neurotransmitters play in the process.

[unreadable] DESCRIPTION (provided by applicant): Five years of renewed support are requested for three Core modules in the Department of Brain and cognitive Sciences at the Massachusetts Institute of Technology. Ours is a growing department which at are sent has ten NEI-supported investigators who carry out research on vision, the visual system and the oculomotor system. Due to major support from the McGovern family and the Picower Foundation, two major new centers have been formed at MIT (the McGovern Institute for Brain Research and the Picower Center for Learning and Memory) in which numerous new appointments will be made the next five years, with several of them in vision and oculomotor control. Some of these appointments have already been made. Presently we have 19 grants from the National Eye Institute. The research carried out by the ten investigators of the [unreadable] Core Group includes the following areas of research: (1) neurophysiological studies of the visual and [unreadable] oculomotor systems, (2) anatomical studies of the visual and oculomotor systems, (3) developmental studies of the vision and visuomotor function, (4) psychophysical studies of visual functions in non-human primates, (5) psychophysical studies of visual functions in normal human and patient populations, (6) computational analyses of vision and eye movement, and (7) imaging studies to elucidate the roles various visual areas play in image processing Two of the modules supported by this Core Grant, the Instrument Shop and the Electronics Shop, are in extensive use by the Core Group. During the past four years these investigators have been very productive and have published extensively as documented in this application. The Core Modules have made significant contributions to the overall research efforts of this group and have fostered interaction among investigators involved in vision and visuomotor research. Continued support of these two Core Facilities will be of great benefit to our future investigations. Additionally, we are requesting support for a new module to support ongoing and planned imaging studies conducted by eye researchers at MIT. If funded, this module will provide a central support facility for functional brain imaging by NEI-supported investigators in the BCS department. [unreadable] [unreadable] [unreadable]