James W. Gnadt - US grants

DESCRIPTION: (Adapted from the applicant's abstract.) Recently, considerable progress has been made in understanding the brainstem mechanisms involved in ocular vergence and lens accommodation, two of the three components of the highly integrated 'near response.' This work has emphasized the inadequacies of our knowledge of how information related to depth is processed and transmitted to the brainstem oculomotor areas. Clearly, the sensory processing of cues to depth utilizes primary visual cortex. Many striate and prestriate neurons in the monkey are sensitive to binocular disparity and the high spatial frequencies necessary for accurate binocular alignment and the adjustment of accommodation. Beyond this however, our understanding of the cortical mechanisms of perceptual and oculomotor responses related to depth is fragmentary. There are clear indications that posterior partial cortex may be involved in some of the processing of this information. Studies of lesions in humans have demonstrated deficits in both the perception of depth and in oculomotor responses to visual targets in depth. Recent neurophysiological studies in posterior parietal cortex of monkeys have shown that some neurons respond selectivity to target depth or to the oculomotor response associated with these targets. Anatomically, posterior parietal cortex receives input from prestriate visual areas and sends projections into the midbrain and pons. This project will consist of a series of neurophysiological experiments in behaving primates to investigate the involvement of parietal cortical neurons in visual-motor behavior in the depth dimension. Monkeys will be trained to fixate and follow visual targets while the responses of individual neurons to the visual stimulation and the motor behavior is investigated. Several behavioral tasks will be employed using a specialized visual display and recording apparatus which will allow independent control and measure of important aspects of the sensory and motor parameters. Specifically, the relation of the neurons to stimulus form, position, motion binocular disparity and accommodative demand will be determined; as well as to the parameters of binocular eye position and velocity, and to lens accommodation. Elucidation of basic mechanisms of parietal function related to depth perception and to disjunctive eye movements is likely to provide valuable insights into the disorders involving disease of the parietal cortex and into the neurology of the motor control of the near response triad in general.

DESCRIPTION: The ultimate goals of this proposal are to identify organizational principles of information flow and integration in sensorimotor systems of the brain. The model perhaps best suited for this is the oculomotor system, where visual percepts are integrated with high order behavioral processes for the production of highly precise saccadic eye movements. By studying this "simple" behavior, we hope to understand some of the general mechanisms by which the brain produces all behavior. Studying the brain in awake, behaving subjects allows a degree of insight into high order brain functions that is not possible in other experimental models. Globally, these studies help us to understand the biological solutions for the problem of information flow in the brain and the transformation of visual signals for movement control. This is important not only for understanding the biology of eye movements in humans, but to the problem of movement control and behavior in general. We propose to study the activity of individual neurons in the posterior parietal cortex and the superior colliculus during simple visual and eye movement behavior. We have shown that parietal neurons are part of the process for translating the spatial position of visual stimuli into the commands for moving the eyes. We will identify individual neurons that project from parietal cortex to other oculomotor centers (the superior colliculus and the frontal eye fields). By studying these neurons we can determine the transfer of information from one brain area to the next. We will use both empirical and modeling techniques. We will construct models of the transformations determined from the biological experiments. We will then use the models to make new predictions that can be tested in the lab.

Oculomotor behavior as an "ideal system" for the study of the neurophysiologic mechanisms of voluntary and reflex behavior. As an overt and measurable behavior, motor systems are ideal for study of the fundamental mechanisms for how the brain transforms sensory inputs and volitional commands into outputs. Among the motor systems, eye movements have the advantage of being relatively simple. In order to study volitional behavior in vivo, we use chronic recording techniques in trained primates. In one set of experiments, we are studying the fundamental cellular and circuit mechanism for generating saccadic eye movements, the high-velocity eye flicks that one uses to scan the surrounding environment. The brain circuit that generates saccadic behavior is essentially a biologic machine that acts like a central pattern generator, a closed-loop neural circuit that creates a stereotyped motor output in response to inputs from higher centers. Like any machine, one can attempt to understand how it works by "reverse engineering." That is, given the machine's output, how do the internal circuits function to produce that output? One systems engineering approach is to inject characteristic input signals at critical points within the circuit and compare the output to quantitative predictions based on assumptions about the biological mechanisms. Using this approach, we have addressed several fundamental issues in oculomotor physiology, which in turn reveals brain mechanisms that are general to all behavior. By studying the brain in live and behaving subjects, we obtain fundamental insight into how it computes, plans movements and represents information. We come to understand the brain's wiring diagrams and how networks of interconnected neurons function together as an effective biologic machine. Such basic biology research is essential as the fundamental underpinning for understanding brain function when compromised by disease or injury. The health relatedness of this research is that the understanding of how the normal, healthy brain works is a sine qua non for understanding the human condition in health and in illness.