During fixation, the eyes are not still, but often exhibit microsaccadic movements. The function of microsaccades is controversial, largely because the neural mechanisms responsible for their generation are unknown. Here we show that the superior colliculus (SC), a retinotopically organized structure involved in voluntary-saccade target selection, plays a causal role in microsaccade generation. Neurons in the foveal portion of the SC increase their activity before and during microsaccades with sizes of only a few minutes of arc, and exhibit selectivity for the direction and amplitude of these movements. Reversible inactivation of these neurons significantly reduces microsaccade rate without otherwise compromising fixation. These results, coupled with computational modeling of SC activity, demonstrate that microsaccades are controlled by the SC, and explain the link between microsaccades and visual attention.Microsaccades are the very small (typically <12 min arc), involuntary, fast eye movements that occur during fixation (1-3). The behavioral properties and functional significance of microsaccades have been extensively studied -and sometimes vigorously debated -for many years (1-14). However, the neural mechanisms responsible for their generation are unexplored. We now show that the superior colliculus (SC), a retinotopically organized structure known to be important for selecting and initiating voluntary eye movements (15)(16)(17), is also part of the neural mechanism that controls microsaccades.We analyzed SC activity associated with 15,205 microsaccades that occurred while monkeys fixated a small stationary spot (18). Each fixation trial lasted for 3,500 ms resulting in many microsaccades with a variety of directions and amplitudes (Fig. 1A,Supp. Fig. S1). These movements had dynamics like those of larger saccades (3) (Supp. Fig. S1A), consistent with evidence that pre-motor neurons (downstream from the SC) are active during movements as small as 12-15 min arc (19).We targeted neurons in the rostral pole of the SC, which represents foveal goal locations (18,20). Figure 1A shows the spiking activity of a neuron in the left SC during a single trial containing 9 microsaccades (highlighted in green). The neuron exhibited changes in activity that were correlated with microsaccades. For example, the microsaccades labeled 1 and 2 in Fig. 1A were predominantly downward and leftward, respectively, and both were associated with a reduction in the neuron's activity. In contrast, small, predominantly rightward † This manuscript has been accepted for publication in Science. This version has not undergone final editing. Please refer to the complete version of record at http://www.sciencemag.org/. The manuscript may not be reproduced or used in any manner that does not fall within the fair use provisions of the Copyright Act without the prior, written permission of AAAS.*To whom correspondence should be addressed. E-mail: zhafed@salk.edu. NIH Public Access Author ManuscriptScience. Author manuscript; available in P...

Ocular fixation is a dynamic process that is actively controlled by many of the same brain structures involved in the control of eye movements, including the superior colliculus, cerebellum and reticular formation. In this article, we review several aspects of this active control. First, the decision to move the eyes not only depends on target-related signals from the peripheral visual field, but also on signals from the currently fixated target at the fovea, and involves mechanisms that are shared between saccades and smooth pursuit. Second, eye position during fixation is actively controlled and depends on bilateral activity in the superior colliculi and medio-posterior cerebellum; disruption of activity in these circuits causes systematic deviations in eye position during both fixation and smooth pursuit eye movements. Third, the eyes are not completely still during fixation but make continuous miniature movements, including ocular drift and microsaccades, which are controlled by the same neuronal mechanisms that generate larger saccades. Finally, fixational eye movements have large effects on visual perception. Ocular drift transforms the visual input in ways that increase spatial acuity; microsaccades not only improve vision by relocating the fovea but also cause momentary changes in vision analogous to those caused by larger saccades.This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.

The caudal fastigial nucleus (cFN) is a major nucleus by which the cerebellum influences the accuracy of saccades. In head-restrained monkeys generating saccades from a fixation light-emitting diode (LED) toward a flashed target LED, we analyzed the effects of unilateral pharmacological inactivation of cFN on horizontal, vertical, and oblique saccades. When animals were viewing the fixation LED, usually after one or more correction saccades, the positions of the eyes were slightly offset in comparison with the positions maintained before the injection (average offset = 1.1 degrees). The offset was ipsilateral to the injected side and did not depend on the target location. The horizontal component of all ipsilesional saccades was hypermetric and associated with a 32-42% increase in the amplitude of the deceleration displacement without significant change in the amplitude of the acceleration displacement. The horizontal component of all contralesional saccades was hypometric and associated with a decrease in the peak velocity and in the acceleration amplitude (30-35% decrease) without significant change in the deceleration amplitude. The amplitude of vertical saccades was not systematically affected, but their trajectory was always deviated toward the injected side. They missed the target with an error that depended on saccade duration or amplitude. If any, the effects of muscimol injections on the vertical component of oblique saccades were very small. The changes in fixation and the dysmetria are both viewed as consequences of an impairment in the cFN bilateral influence on the burst neurons located in the left and right brain stem.

When primates maintain their gaze directed toward a visual target (visual fixation), their eyes display a combination of miniature fast and slow movements. An involvement of the cerebellum in visual fixation is indicated by the severe gaze instabilities observed in patients suffering from cerebellar lesions. Recent studies in non-human primates have identified a cerebellar structure, the fastigial oculomotor region (FOR), as a major cerebellar output nucleus with projections toward oculomotor regions in the brain stem. Unilateral inactivation of the FOR leads to dysmetric visually guided saccades and to an offset in gaze direction when the animal fixates a visual target. However, the nature of this fixation offset is not fully understood. In the present work, we analyze the inactivation-induced effects on fixation. A novel technique is adopted to describe the generation of saccades when a target is being fixated (fixational saccades). We show that the offset is the result of a combination of impaired saccade accuracy and an altered encoding of the foveal target position. Because they are independent, we propose that these two impairments are mediated by the different projections of the FOR to the brain stem, in particular to the deep superior colliculus and the pontomedullary reticular formation. Our study demonstrates that the oculomotor cerebellum, through the activity in the FOR, regulates both the amplitude of fixational saccades and the position toward which the eyes must be directed, suggesting an involvement in the acquisition of visual information from the fovea.

During visual fixation, the image of an object is maintained within the fovea. Previous studies have shown that such maintenance involves the deep superior colliculus (dSC). However, the mechanisms by which the dSC supports visual fixation remain controversial. According to one view, activity in the rostral dSC maintains gaze direction by preventing neurons in the caudal dSC from issuing saccade commands. An alternative hypothesis proposes that gaze direction is achieved through equilibrium of target position signals originating from the two dSC. Here we show in monkeys that artificially reducing activity in the rostral half of one dSC results in a biased estimate of target position during fixation, consistent with the second hypothesis, rather than an inability to maintain gaze fixation as predicted by the first hypothesis. After injection of muscimol at rostral sites in the dSC, fixation became more stable since microsaccade rate was reduced rather than increased. Moreover, the scatter of eye positions was offset relative to pre-inactivation baselines. The magnitude and the direction of the offsets depended upon both the target size and the injected site in the collicular map. Other oculomotor parameters, such as the accuracy of saccades to peripheral targets and the amplitude and velocity of fixational saccades, were largely unaffected. These results suggest that the rostral half of the dSC supports visual fixation through a distributed representation of behaviorally-relevant target position signals. The inactivation-induced fixation offset establishes the foveal visual stimulation that is required to restore the balance of activity between the two dSC.

The primate superior colliculus (SC) is often viewed as composed of two distinct motor zones with complementary functions: a peripheral region that helps generate saccades to eccentric targets and a central one that maintains fixation by suppressing saccades. Here, we directly tested the alternative interpretation that topography in the SC is not strictly motor, nor does it form two distinct zones, but instead forms a single map of behaviorally relevant goal locations. Primates tracked the invisible midpoint between two moving stimuli, such that the stimuli guiding tracking were peripheral whereas the inferred movement goal was foveal and parafoveal. Temporary inactivation of neurons in the central portion of the topographic map of the SC, representing the invisible goal, caused stable offsets in eye position during tracking that were directed away from the retinotopic position encoded by the inactivated SC site. Critically, these offsets were not accompanied by a systematic inability to generate or suppress saccades, and they were not fully explained by motor deficits in saccades, smooth pursuit, or fixation. In addition, the magnitude of the offset depended on the eccentricity of the inactivated site as well as the degree of spatial uncertainty associated with the behavioral goal. These results indicate that gaze control depends on the balance of activity across a map of goal locations in the SC, and that by silencing some of the neurons in the normally active population representing the behavioral goal, focal inactivation causes a biased estimate of where to look.

Rigorous behavioral studies made in human subjects have shown that small-eccentricity target displacements are associated with increased saccadic reaction times, but the reasons for this remain unclear. Before characterizing the neurophysiological foundations underlying this relationship between the spatial and temporal aspects of saccades, we tested the triggering of small saccades in the male rhesus macaque monkey. We also compared our results to those obtained in human subjects, both from the existing literature and through our own additional measurements. Using a variety of behavioral tasks exercising visual and nonvisual guidance of small saccades, we found that small saccades consistently require more time than larger saccades to be triggered in the nonhuman primate, even in the absence of any visual guidance and when valid advance information about the saccade landing position is available. We also found a strong asymmetry in the reaction times of small upper versus lower visual field visually guided saccades, a phenomenon that has not been described before for small saccades, even in humans. Following the suggestion that an eye movement is not initiated as long as the visuo-oculomotor system is within a state of balance, in which opposing commands counterbalance each other, we propose that the longer reaction times are a signature of enhanced times needed to create the symmetry-breaking condition that puts downstream premotor neurons into a push-pull regime necessary for rotating the eyeballs. Our results provide an important catalog of nonhuman primate oculomotor capabilities on the miniature scale, allowing concrete predictions on underlying neurophysiological mechanisms. NEW & NOTEWORTHY Leveraging a multitude of neurophysiological investigations in the rhesus macaque monkey, we generated and tested hypotheses about small-saccade latencies in this animal model. We found that small saccades always take longer, on average, than larger saccades to trigger, regardless of visual and cognitive context. Moreover, small downward saccades have the longest latencies overall. Our results provide an important documentation of oculomotor capabilities of an indispensable animal model for neuroscientific research in vision, cognition, and action.

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