Smooth-pursuit eye movements allow primates to track moving objects. Efficient pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Prediction depends on expectation of future object motion, storage of motion information and use of extra-retinal mechanisms in addition to visual feedback. We present behavioral evidence of how cognitive processes are involved in predictive pursuit in normal humans and then describe neuronal responses in monkeys and behavioral responses in patients using a new technique to test these cognitive controls. The new technique examines the neural substrate of working memory and movement preparation for predictive pursuit by using a memory-based task in macaque monkeys trained to pursue (go) or not pursue (no-go) according to a go/no-go cue, in a direction based on memory of a previously presented visual motion display. Single-unit task-related neuronal activity was examined in medial superior temporal cortex (MST), supplementary eye fields (SEF), caudal frontal eye fields (FEF), cerebellar dorsal vermis lobules VI–VII, caudal fastigial nuclei (cFN), and floccular region. Neuronal activity reflecting working memory of visual motion direction and go/no-go selection was found predominantly in SEF, cerebellar dorsal vermis and cFN, whereas movement preparation related signals were found predominantly in caudal FEF and the same cerebellar areas. Chemical inactivation produced effects consistent with differences in signals represented in each area. When applied to patients with Parkinson's disease (PD), the task revealed deficits in movement preparation but not working memory. In contrast, patients with frontal cortical or cerebellar dysfunction had high error rates, suggesting impaired working memory. We show how neuronal activity may be explained by models of retinal and extra-retinal interaction in target selection and predictive control and thus aid understanding of underlying pathophysiology.

Changes in oculomotor behaviors with aging were studied in normal young and elderly subjects. Saccadic eye movements induced by presentation of a visual target were analyzed. Elderly subjects commonly showed an elongation of the time to locate the target, accompanied by an increase in reaction times (mean increase, 100 ms) and a decrease in saccadic velocities. The decrease in the velocity was particularly notable when a large-amplitude saccade was executed. In spite of the slowed motor responses, most elderly subjects preserved the function necessary to execute a correct saccade toward the visual target. The saccadic slowing was accompanied by an increase in saccade duration. Although a longer time was necessary for elderly subjects to locate the target, the accuracy of the initial saccades was not different from that of young subjects. One group of elderly subjects showed extremely long reaction times. These subjects, displaying no abnormal neurological symptoms, were not able to locate the visual target with initial saccades. They had to execute multistep saccades typically seen in patients with degenerative neurological diseases.

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