Charles Gross - US grants

The long-term goal of this research is to contribute to the understanding of the physiological mechanisms of visual perception and visually guided behavior in order to facilitate the treatment, amelioration and prevention of disorders of vision caused by trauma, disease and developmental abnormalities. In addition to striate cortex, a vast expanse of the cerebral cortex of primates is involved in visual perception and visually guided behavior. This cortex includes prestriate cortex, inferior temporal cortex (IT) and the superior temporal polysensory area (STP). Ongoing research on the functions of prestriate cortex, IT cortex and STP cortex will be continued using physiological, anatomical and behavioral methods. One major aim is to determine the role of the prestriate area MT in the perception of movement and the neural circuitry underlying this role. A second major aim is to analyze the role of the superior temporal polysensory area in orientation, localization, and eye movements, to determine the source of its visual input and to ascertain the role it plays in the visual functions that survive damage to the geniculostriate system, i.e. in "blind sight". A third major aim is to analyze further the role of the inferior temporal cortex in shape and face recognition in order to understand the perceptual deficits that follow its removal. These aims are directly relevant to such health related problems as the development of visual protheses, the treatment of perceptual deficits after cortical damage, and the optimal utilization of sensory capacities after brain damage that results in impaired vision or blindness.

The long-term goal of this research is to contribute to the understanding of the physiological mechanisms of visual perception and visually guided behavior in order to facilitate the treatment, amelioration and prevention of disorders of vision caused by trauma, disease and developmental abnormalities. In addition to striate cortex, a vast expanse of the cerebral cortex of primates is involved in visual perception and visually guided behavior. This cortex includes prestriate cortex, inferior temporal cortex (IT) and the superior temporal polysensory area (STP). Ongoing research on the functions of prestriate cortex, IT cortex and STP cortex will be continued using physiological, anatomical and behavioral methods. One major aim is to determine the role of the prestriate area MT in the perception of movement and the neural circuitry underlying this role. A second major aim is to analyze the role of the superior temporal polysensory area in orientation, localization, and eye movements, to determine the source of its visual input and to ascertain the role it plays in the visual functions that survive damage to the geniculostriate system, i.e. in "blind sight". A third major aim is to analyze further the role of the inferior temporal cortex in shape and face recognition in order to understand the perceptual deficits that follow its removal. These aims are directly relevant to such health related problems as the development of visual protheses, the treatment of perceptual deficits after cortical damage, and the optimal utilization of sensory capacities after brain damage that results in impaired vision or blindness.

Inferior temporal cortex is necessary for normal visual perception and visual learning in adult humans and monkeys. Several line of behavioral, anatomical and physiological evidence suggest that inferior temporal cortex continues to develop in the first year of post-natal life. This possibility will be examined by studying the properties of inferior temporal neurons in normally reared macaques at various times in the first year of life and comparing them to the properties of inferior temporal neurons in adult monkeys. The single neuron properties studied will include responsiveness, modality specificity, receptive field size and location, and stimulus selectively. The role of specific visual experience in the development of the properties of inferior temporal neurons will also be investigated. In adult macaques some inferior temporal neurons respond selectively to faces. In animals raised from birth for one year without exposure to faces the incidence of face-selective neurons will be compared to that in normally reared animals. Some animals will also be raised with extensive exposure to an artifical stimulus and the selectivity of inferior temporal cells for this stimulus will be subsequently tested. The proposed research should enhance understanding of the development of human visual learning and perception and its interference by disease, trauma and developmental disorders.

It is believed that visual perception occurs largely based on interactions of nerve cells, or neurons, in the visual cortex of the brain. The visual cortex itself is a structure composed of several layers of different classes on neurons. These classes are distinguished by the shape of the cells, their connections, their response to particular patterns of light stimulation or motion or color, and by the chemicals called neurotransmitters that the neurons secrete at their functional connections, called synapses. Two important neurotransmitters of a group called mono-amines are known as NE (norepinephrine) and 5-HT (5-hydroxy- tryptamine). The pathways for neurons in the brain to the cells they innervate are fairly well known for both these compounds, and monoamines are known to modulate activity in several neural systems. The equipment provided will allow a new approach to understanding modulation of cortical activity. The study is a preliminary effort to determine at the level of single cells in the well-described layers of the primate visual cortex, how information processing is modulated by the similarly layered and specifically connected neurons secreting monoamines. Highly controlled visual stimuli will be used to excite visual cortical cells, and when the responses are characterized, highly localized pharmacological applications of monoamines will be made by microelectrode. Changes in visual properties attributable to the monoamines which are specific to a cell class, lamina, or cortical area may be described in terms of their potential significance for perception and behavior. This work will have impact on psychology of arousal and attention, as well as on visual and sensory neuroscience, and provide a novel bridge between these communities.

One region of the brain that appears to be involved in storage of visual information is the inferior temporal ("IT") cortex. Area IT has been implicated by behavioral studies to be a major site for visual perception or visual memory, and physiological studies on single nerve cell activity in area IT have shown particular sensitivity to spatial visual patterns. This project will combine physiology and behavior to look at the activity of single cells during either a visual task or a task requiring memory of of a visual image. Tests will be run to see if an IT neuron that responds to a visual stimulus in a serial sequence also will respond similarly during a task requiring mental recall of that sequence, without the visual stimulus itself being present. Results of this novel exploratory approach will be very important to our understanding of formation and maintenance of mental images, and will have impact on cognitive neuroscience and perceptual psychology, in additon to visual and sensory neuroscience.

It is known that there is a range of recovery to different kinds of brain damage. In the visual system of humans, damage to only the visual cortex of the brain often leaves residual functional vision, called "blindsight", that presumably depends on pathways from the eye to areas other than primary visual cortex. There is evidence that sparing or recovery of visual function is greater when cortical damage occurs during infancy rather than in an adult. This project investigates some of the mechanisms by which such visual recovery in very young animals may be more effective than recovery of older animals. Visual detection, localization and discrimination will be assessed for the field of vision normally represented in the excised tissue (the "field defect"), and recovery will be tracked as a function of time and of practice. Behavioral responses later will be compared to responses of single nerve cells in the visual regions of the brain outside the lesioned areas, and anatomical studies will explore the development of changes in connectivity. Results are likely to clarify how recovery in infants occurs better than in adults, and so will be very important to our understanding of the organization and development of the primate and human visual system.

9871186 With instrumentation provided by the National Science Foundation Drs. Marcia Johnson, Jonathan Cohen and Charles Gross will establish a Center for Cognitive and Behavioral Neuroscience (CCBN) at Princeton University. The Center will focus on understanding the brain mechanisms underlying the cognitive and motivational processes that control behavior, as well as the development of new methods for cognitive neuroscientific research. Research at all levels, from the molecular to the behavioral, will explore the brain mechanisms and subsystems underlying higher cognitive functions (such as attention, memory and decision making), and the closely-related affective processes that govern reward and motivation. Of central interest are the ways in which normal behavior is controlled by higher level goals and regulated by states of arousal, motivation and reward, as well as the ways in which these systems can fail. The Center will couple methods developed during one hundred years of research in physiological and cognitive psychology with important new technologies for investigating the brain. This combination promises to open the way to understand functions of the mind once considered intractable, such as how consciousness and thought emerge from the underlying structures of the brain, what biological systems control emotion and behavior, and what chemical, structural and functional anomalies underlie cognitive deficits and psychopathologies. Several complementary approaches will be employed: fMRI and Event-related Potential (ERP) will be used to examine the structure and function of the brain in conscious human subjects performing cognitive tasks designed to analyze higher mental processes. The separate activity of each of multiple brain cells can be measured. Likewise the expression of particular molecules in individual brain cells as a result of engaging in a specific behavior will also be determined. Two closely related laboratories will be included in the CCBN. An Im aging and Modeling Facility (IMF) will house staff and equipment for the analysis of data sets obtained from fMRI and human electrophysiological studies, and for support of neural network simulation modeling. It will also provide facilities for on site ERP, eye movement and pupilometric recording. During the initial phase of Center development, fMRI data will be gathered at a site less than a mile from the Princeton campus and through collaborations with investigators at other institutions. A closely related Neurotechnology (NTF) Facility will support research at the cellular, molecular and biochemical level. The facility will house modern equipment necessary to conduct analyses of neural substrates of behavior at all of these levels in a variety of mammals, from rodents to primates. Central to proposed research at the IMF is a SGI Symmetric Multiprocessor and associated workstations, microcomputers, networking and software. ERP and eye movement recording equipment, including a Neuro Scan 128 channel SYN-AMPS will also be purchased. A Nikon PCM 2000 confocal microscope system and related computer software will be acquired for use by the NTF. Both graduate and undergraduate students will have access to the laboratories and the instrumentation therefore will serve important educational and training functions.