David A. Robinson - US grants

The long-term objectives are to work out the neural wiring of the oculomotor system. Data are collected from human and animal experiments and interpreted in the form of control-systems models to try and provide mechanistic explanations for human oculomotor disorders. One specific aim is to try and locate the neural integrator that converts eye-velocity to eye-position commands. Lesions of the vestibular nucleus in monkeys may implicate this nucleus and recording from tonic cells in the reticular formation may reveal their involvement. The feasibility of the reverberating-collateral hypothesis for the integrator will be tested by a computer model. Another specific aim is to find whether or not plasticity of the vestibulo-ocular reflex (vor) is in the flocculus by surveying cell types in the cat flocculus, studying the appropriate types during visually-induced changes in the gain of the vor and the response of such cells to an interruption of climbing fiber signals from the inferior olive by injection of a local anesthetic. Another aim is to demonstrate plasticity in the human pursuit system by utilizing the dissociation of neural commands and eye movements that occur in muscle palsy and to incorporate the findings in a model of pursuit. Another aim is to record from burst neurons in the monkey that create vertical saccades and find out if their planes of action lie near those of the canals or eye muscles by rotating them in and around such planes to evoke quick phases. Another aim is to utilize very large eye and head movements to study and model the interaction of the vor and neural saccadic commands. The final aim is to demonstrate that subjects can cancel (suppress) their vor in roll. Since there is no torsional pursuit, this implies that there must exist a neurological system distinct from pursuit to cancel the vor. These projects are designed to quantify the behavior of human oculomotor subsystems, identify and describe new subsystems, describe interactions between them, and provide a neural scheme in the form of a model to explain their normal behavior. These measurements form a basis for the diagnosis of eye movement disorders in human beings and our hypotheses of signal processing by the neural substrates of these systems can often provide a hypothesis for the etiology of those disorders. These projects are also directed to studying the extent to which these systems can recover normal function following dysmetria caused by trauma or disease and the neural mechanisms underlying this plasticity.

The long-term objective is to understand the oculomotor system. The applied goals are to provide data for more quantitative and sensitive clinical tests that will help in determining eh locations of brain lesions. We also seek the basic mechanisms by which the nervous system repairs dysmetria after disease or trauma. The basic goals are to discover how the nervous system processes neural signals in regulating the control of movement; in particular, how this is accomplished by networks of neurons that can learn. Four initial projects are aimed at these goals. The first uses a new theoretical approach: a backward-propagating model of a learning neural network. A major feature of this network is that the tasks are distributed among its neurons just as we observed in the oculomotor system. Pursuit, saccadic and vestibular commands are distributed over the vestibulaR-oculomotor regions of the caudal pons. Action directions of second-order anal afferents are distributed over all directions as are the action directions of burst neurons that create saccades. These patterns can be accounted for with this learning network. This is the first attempt to model at the nerve-network level in the oculomotor system and we hope that it will initiate a major move in this direction. A second project addresses the neural integrator which changes eye-velocity into eye-position commands. We have located it in the nucleus prepositus hypoglossi and vestibular nucleus and believe that it depends heavily on commissural connections. We will investigate this in the alert monkey by microstimulation and micro injections of a local anesthesia in this region to provide evidence that may suggest how the neural integrator works. A third project investigates predictive tracking of the saccadic and pursuit systems and how they interact. We first explore how many state changes (change in target position or velocity for given durations) can be stored in their internal pattern generators. We next ask to what extent random fluctuations in one system interfere with the ability to predict but we have very little by way of a normal data base. The fourth project involves motor learning in the control of the gain of the vestibulo-ocular reflex (VOR) in the cat with emphasis on the role of climbing fibers. We intend to record form Purkinje cells in the flocculus and measure the gain of the VOR in normal or gain-adapted animals while either stimulating or anesthetizing the climbing fibers. We hope to provide information to test the hypothesis that motor learning is stored in the cerebellum.