End Of Saccade Research Articles

Learning Signals from the Superior Colliculus for Adaptation of Saccadic Eye Movements in the Monkey

Vital to motor learning is information about movement error. Using this information, the brain creates neural learning signals that instruct a plasticity mechanism to produce appropriate behavioral learning. Little is known, however, about brain structures that generate learning signals for voluntary movements. Here we show that signals from the superior colliculus (SC) can drive learning in saccadic eye movements in the monkey. Electrical stimulation of the SC deeper layers, subthreshold for evoking saccades, was applied immediately (approximately 60 ms) after the end of horizontal saccades in one or both directions. The target disappeared during saccades and remained invisible for 1 s to eliminate effects of postsaccadic visual information. Repetitive pairing of saccades with SC stimulation produced a marked, two-dimensional shift in movement endpoint relative to the target location. The elicited endpoint shift took a gradual, approximately exponential course over several hundred saccades as in visually induced saccade adaptation. The shift in movement endpoint remained nearly unchanged after stimulation was discontinued, indicating involvement of neuronal plasticity. When both rightward and leftward saccades were paired with stimulation, their endpoints shifted in similar directions. The endpoint shift was directed contralaterally to the stimulated SC. The direction and size of the endpoint shift depended on the stimulation site in the SC. We propose that the SC, a brainstem structure long known to be crucial for saccade execution, is involved in motor learning and sends signals that dictate the direction of adaptive shift in saccade endpoint.

Role of Glycinergic Inhibition in Shaping Activity of Saccadic Burst Neurons

The immediate premotor signals for saccades are created at the level of medium-lead burst neurons (MLBNs). During fixations, MLBNs receive tonic inhibition from omnipause neurons (OPNs), which use glycine as a neurotransmitter. To elucidate the role of this inhibition, we studied discharge patterns of horizontal MLBNs following iontophoretic application of strychnine, a glycine-receptor antagonist, in alert cats. Three-barrel micropipettes were used for extracellular recording and iontophoresis. After application of strychnine, MLBNs exhibited spontaneous discharge and visual responses during intersaccadic intervals. Spikes were evoked by single-pulse stimulation of the contralateral superior colliculus (SC). These results show that MLBNs receive substantial excitatory input during intersaccadic intervals and that inhibitory action of OPNs is indeed necessary to prevent MLBNs from firing. Strychnine also affected saccade-related activity of MLBNs. The burst of activity, as in normal conditions, declined rapidly before the end of saccades but was followed by low rate spike activity, which continued beyond the end of saccades. This suggests that in normal conditions, the termination of saccades is determined by resumed inhibitory action of OPNs and not by termination of excitatory input to MLBNs. In addition, the firing rate and the number of spikes during saccades increased after strychnine application, suggesting that MLBNs receive glycinergic inhibition of non-OPN origin as well. We conclude that glycinergic inhibition plays essential roles in the maintenance of stable fixation, the termination of saccades, and the regulation of saccade size and velocity.

What is adapted in saccadic adaptation?

What is adapted in saccadic adaptation?

Head-unrestrained gaze adaptation in the rhesus macaque.

The ability to adjust the amplitude of gaze shifts in response to persistent visual errors ("gaze adaptation") has been investigated primarily by introducing visual errors at the end of saccades produced by head-restrained primates. Very little is known about the behavior and neural mechanisms underlying gaze adaptation when the head is free to move. We tested alternative hypotheses about the signals that are altered during gaze adaptation by increasing (25 degrees --> 50 degrees ; "forward adaptation") or decreasing (50 degrees --> 25 degrees ; "backward adaptation") the size of large, head-unrestrained gaze shifts. In our three rhesus monkey subjects, changes to primary gaze shift amplitude occurred regardless of the particular combinations of eye and head movements that made up the amplitude-altered gaze shifts. The relative changes to eye and head movements that occurred during adaptation could be predicted based on the magnitude of gaze adaptation and the positions of the eyes in the orbits at gaze onset. These results are consistent with the hypothesis that gaze adaptation occurs at the level of a gaze shift command and inconsistent with hypotheses based on the assumption that gaze adaptation results from alterations to eye- and/or head-specific signals.

Cerebellar-dependent motor learning is based on pruning a Purkinje cell population response

The improvement of motor behavior, based on experience, is a form of learning that is critically dependent on the cerebellum. A well studied example of cerebellar motor learning is short-term saccadic adaptation (STSA). In STSA, information on saccadic errors is used to improve future saccades. The information optimizing saccade metrics is conveyed by Purkinje cells simple spikes (PC-SS) because they are the critical input to the premotor circuits for saccades. We recorded PC-SS of monkeys undergoing STSA to reveal the code used for improving behavior. We found that the discharge of individual PC-SS was unable to account for the behavioral changes. The PC-SS population burst (PB), however, exhibited changes that closely paralleled the qualitatively different changes of saccade kinematics associated with gain-increase and gain-decrease STSA, respectively. Gain-increase STSA, characterized by an increase in saccade duration, replicates the relationship between saccade duration and the end of the PB valid for unadapted saccades. In contrast, gain-decrease STSA, which sports normal saccade duration but reduced saccadic velocity, is characterized by a PB that ends well before the adapted saccade. This suggests that the duration of normal as well as gain-increased saccades is determined by appropriately setting the end of PB end. However, the duration of gain-decreased saccades is apparently not modified by the cerebellum because the PB signals ends too early to determine saccade end. In summary, STSA, and most probably cerebellar-dependent learning in general, is based on optimizing the shape of a PC-SS population response.

Saccade control and eye–hand coordination in optic ataxia

The aim of this work was to investigate ocular control in patients with optic ataxia (OA). Following a lesion in the posterior parietal cortex (PPC), these patients exhibit a deficit for fast visuo-motor control of reach-to-grasp movements. Here, we assessed the fast visuo-motor control of saccades as well as spontaneous eye–hand coordination in two bilateral OA patients and five neurologically intact controls in an ecological “look and point” paradigm. To test fast saccadic control, trials with unexpected target-jumps synchronised with saccade onset were randomly intermixed with stationary target trials. Results confirmed that control subjects achieved visual capture (foveation) of the displaced targets with the same timing as stationary targets (fast saccadic control) and began their hand movement systematically at the end of the primary saccade. In contrast, the two bilateral OA patients exhibited a delayed visual capture, especially of displaced targets, resulting from an impairment of fast saccadic control. They also exhibited a peculiar eye–hand coordination pattern, spontaneously delaying their hand movement onset until the execution of a final corrective saccade, which allowed target foveation. To test whether this pathological behaviour results from a delay in updating visual target location, we had subjects perform a second experiment in the same control subjects in which the target-jump was synchronised with saccade offset. With less time for target location updating, the control subjects exhibited the same lack of fast saccadic control as the OA patients. We propose that OA corresponds to an impairment of fast updating of target location, therefore affecting both eye and hand movements.

Hand position modulates saccadic activity in the frontal eye field

Recent neurophysiological studies have begun to uncover the neuronal correlates of eye hand coordination. This study was designed to test whether the frontal eye field (FEF) saccadic activity is modulated by hand position. Single neurons were recorded in two macaque monkeys performing visually guided saccades while holding their hand at given locations on a touchscreen. To determine the relative contributions of hand vision and its proprioception, monkeys executed the task with or without vision of the hand. We found that saccadic activity of more than half of the neuronal sample (54%; n=130) was dependent on hand position relative to the saccade end point. Both visual and proprioceptive signals contributed to this modulation. These data demonstrate that the oculomotor function of the FEF takes into account hand position in space.

Eye movements during rapid pointing under risk

We recorded saccadic eye movements during visually-guided rapid pointing movements under risk. We intended to determine whether saccadic end points are necessarily tied to the goals of rapid pointing movements or whether, when the visual features of a display and the goals of a pointing movement are different, saccades are driven by low-level features of the visual stimulus. Subjects pointed at a stimulus configuration consisting of a target region and a penalty region. Each target hit yielded a gain of points; each penalty hit incurred a loss of points. Late responses were penalized. The luminance of either target or penalty region was indicated by a disk which differed significantly from the background in luminance, while the other region was indicated by a thin circle. In subsequent experiments, we varied the visual salience of the stimulus configuration and found that manual responses followed near-optimal strategies maximizing expected gain, independent of the salience of the target region. We suggest that the final eye position is partially pre-programmed prior to hand movement initiation. While we found that manipulations of the visual salience of the display determined the end point of the initial saccade we also found that subsequent saccades are driven by the goal of the hand movement.

Enhanced Motion Sensitivity Follows Saccadic Suppression in the Superior Temporal Sulcus of the Macaque Cortex

The responses of neurons in the middle temporal and medial superior temporal areas of macaque cortex are suppressed during saccades compared with saccade-like stimulus movements. We utilized the short-latency ocular following paradigm to show that this saccadic suppression is followed by postsaccadic enhancement of motion responses. The level of enhancement decays with a time constant of 100 ms from saccade end. The speed of ocular following is also enhanced after saccades and decays over a similar time course, suggesting a link between the neural and behavioral effects. There is some evidence that maximum postsaccadic enhancement occurs when cells are stimulated at their optimum speeds. Latencies of motion responses are saccade dependent: 37 ms for saccade-generated motion, 45 ms for motion in the half-second after saccades, and 70 ms with no prior saccades. The finding that saccades alter response latencies may partially explain perceptual time compression during saccades and time dilation after saccades.

Responses of Collicular Fixation Neurons to Gaze Shift Perturbations in Head-Unrestrained Monkey Reveal Gaze Feedback Control

A prominent hypothesis in motor control is that endpoint errors are minimized because motor commands are updated in real time via internal feedback loops. We investigated in monkey whether orienting saccadic gaze shifts made in the dark with coordinated eye-head movements are controlled by feedback. We recorded from superior colliculus fixation neurons (SCFNs) that fired tonically during fixation and were silent during gaze shifts. When we briefly (<or=700 ms) interrupted gaze shifts by transiently braking head movements, SCFNs fired steadily during brake-induced gaze immobility, and their mean frequency was inversely related to the remaining distance between current gaze position and the target. After head release, a corrective gaze saccade brought gaze on the unseen goal, and SCFN firing frequency peaked. The results support gaze feedback control and show that the SC is part of a network that encodes, during orientation, the distance between eye and target, irrespective of gaze trajectory characteristics.

Discharge Properties of Monkey Tectoreticular Neurons

The intermediate layers of the superior colliculus (SC) contain neurons that clearly play a major role in regulating the production of saccadic eye movements: a burst of activity from saccade neurons (SNs) is thought to provide a drive signal to set the eyes in motion, whereas the tonic activity of fixation neurons (FNs) is thought to suppress saccades during fixation. The exact contribution of these neurons to saccade control is, however, unclear because the nature of the signals sent by the SC to the brain stem saccade generation circuit has not been studied in detail. Here we tested the hypothesis that the SC output signal is sufficient to control saccades by examining whether antidromically identified tectoreticular neurons (TRNs: 33 SNs and 13 FNs) determine the end of saccades. First, TRNs had discharge properties similar to those of nonidentified SC neurons and a proportion of output SNs had visually evoked responses, which signify that the saccade generator must receive and process visual information. Second, only a minority of TRNs possessed the temporal patterns of activity sufficient to terminate saccades: Output SNs did not cease discharging at the time of saccade end, possibly continuing to drive the brain stem during postsaccadic fixations, and output FNs did not resume their activity before saccade end. These results argue against a role for SC in regulating the timing of saccade termination by a temporal code and suggest that other saccade centers act to thwart the extraneous SC drive signal, unless it controls saccade termination by a spatial code.

Evidence for gaze feedback to the cat superior colliculus: discharges reflect gaze trajectory perturbations.

Rapid coordinated eye-head movements, called saccadic gaze shifts, displace the line of sight from one location to another. A critical structure in the gaze control circuitry is the superior colliculus (SC) of the midbrain, which drives gaze saccades by relaying cortical commands to brainstem eye and head motor circuits. We proposed that the SC lies within a gaze feedback loop and generates an error signal specifying gaze position error (GPE), the distance between target and current gaze positions. We investigated this feedback hypothesis in cats by briefly stopping head motion during large ( approximately 50 degrees ) gaze saccades made in the dark. This maneuver interrupted intended gaze saccades and briefly immobilized gaze (a plateau). After brake release, a corrective gaze saccade brought the gaze on goal. In the caudal SC, the firing frequency of a cell gradually increased to a maximum that just preceded the optimal gaze saccade encoded by the position of the cell and then declined back to zero near gaze saccade end. In brake trials, the activity level just preceding a brake-induced plateau continued steadily during the plateau and waned to zero only near the end of the corrective saccade. The duration of neural activity was stretched to reflect the increased time to target acquisition, and firing frequency during a plateau was proportional to the GPE of the plateau. In comparison, in the rostral SC, the duration of saccade-related pauses in fixation cell activity increased as plateau duration increased. The data show that the cat's SC lies in a gaze feedback loop and that it encodes GPE.

Vertical eye movement-related type II neurons with downward on-directions in the vestibular nucleus in alert cats

The vestibular nuclei and the interstitial nucleus of Cajal (INC) have been regarded as key elements of the velocity-to-position integrator for vertical eye movements. This paper reports a class of type II vestibular neurons that receives input from the INC and carries vertical eye movement signals that appear to represent an intermediate stage of the integration process. Extracellular recordings were made from neurons in and near the vestibular nuclei in alert cats. We encountered 39 neurons that exhibited an intense burst of spikes for downward saccades and a position-related tonic activity during intersaccadic intervals (d-type II neurons). They had a very high saccadic sensitivity (4.3+/-2.7 spikes/deg, mean +/- SD) as well as a high position sensitivity (3.2+/-1.6 (spikes/sec)/deg). Unlike the bursts of motoneurons, the bursts of these neurons declined gradually with an exponential-like time course and lasted well beyond the end of saccades. The mean time constant of the burst decay was 139+/-43 ms. The d-type II neurons were excited with disynaptic or trisynaptic latencies following stimulation of the contralateral vestibular nerve. The responses to vertical head rotations suggested inputs from the contralateral posterior canal. The d-type II neurons were excited with short latencies following stimulation of the ipsilateral INC, suggesting that they receive a direct excitatory input from vertical eye movement-related INC neurons with downward on-directions. The d-type II neurons were located in the rostral portion of the vestibular nuclei and the underlying reticular formation. These results suggest that d-type II neurons may be interposed between the burst-tonic neurons in the INC and pure tonic neurons in the vestibular nuclei and contribute to the oculomotor velocity-to-position integration.

What the brain stem tells the frontal cortex. II. Role of the SC-MD-FEF pathway in corollary discharge.

One way we keep track of our movements is by monitoring corollary discharges or internal copies of movement commands. This study tested a hypothesis that the pathway from superior colliculus (SC) to mediodorsal thalamus (MD) to frontal eye field (FEF) carries a corollary discharge about saccades made into the contralateral visual field. We inactivated the MD relay node with muscimol in monkeys and measured corollary discharge deficits using a double-step task: two sequential saccades were made to the locations of briefly flashed targets. To make second saccades correctly, monkeys had to internally monitor their first saccades; therefore deficits in the corollary discharge representation of first saccades should disrupt second saccades. We found, first, that monkeys seemed to misjudge the amplitudes of their first saccades; this was revealed by systematic shifts in second saccade end points. Thus corollary discharge accuracy was impaired. Second, monkeys were less able to detect trial-by-trial variations in their first saccades; this was revealed by reduced compensatory changes in second saccade angles. Thus corollary discharge precision also was impaired. Both deficits occurred only when first saccades went into the contralateral visual field. Single-saccade generation was unaffected. Additional deficits occurred in reaction time and overall performance, but these were bilateral. We conclude that the SC-MD-FEF pathway conveys a corollary discharge used for coordinating sequential saccades and possibly for stabilizing vision across saccades. This pathway is the first elucidated in what may be a multilevel chain of corollary discharge circuits extending from the extraocular motoneurons up into cerebral cortex.

Discharge Patterns of Cerebellar Output Neurons in the Caudal Fastigial Nucleus during Head‐Free Gaze Shifts in Primates

Lesion studies in both human and non-human primates indicate that the cerebellum is important for accurate and stereotyped saccadic eye movements. Based on single-unit recordings and pharmacological inactivations in head-fixed monkeys, we suggested that the caudal fastigial nucleus (CFN) provides the brainstem saccade generator with a burst that helps accelerate contraversive saccades and decelerate ipsiversive ones. Here we examine this suggestion during head-free gaze shifts where there can be a 10-fold difference in saccade duration. First, the timing of the burst does not depend on whether the gaze shift has a head component. When a family of either ipsiversive or contraversive gaze shifts with a variety of saccadic durations is aligned on gaze onset, the high-frequency burst in the associated rasters occurs progressively later as saccade duration increases. Realignment of the same rasters with the end of the saccade reveals a tight timing of burst end with saccade end for all 10 CFN burst neurons studied. The delayed bursts for contraversive saccades were unexpected based on the early burst illustrated in the published head-fixed data. One hypothesis is that the late activity helps terminate contraversive as well as ipsiversive gaze shifts. An alternative explanation is that the late CFN burst could still be used as an excitatory drive to promote the late reacceleration or prolonged velocity plateau that is present during large gaze shifts.

Adaptive modification of saccade size produces correlated changes in the discharges of fastigial nucleus neurons.

Saccade accuracy is known to be maintained by adaptive mechanisms that progressively reduce any visual error that consistently exists when the saccade ends. We used an experimental paradigm known to induce adaptation of saccade size while monitoring the neural correlates of this adaptation. In rhesus monkeys where the medial and lateral recti of one eye were surgically weakened, patching the unoperated eye and forcing the monkey to use the weakened eye induced a gradual increase in saccade size in both eyes until the viewing, weak eye almost acquired the target in one step. Subsequent patching of the weakened eye gradually reversed the situation, so that the saccades in the viewing, normal eye decreased from an initial overshooting to normal. In the caudal fastigial nuclei of unadapted monkeys, neurons typically exhibit an early burst of spikes that is correlated with the onset of contraversive saccades and a later burst of spikes that is correlated with the termination of ipsiversive saccades. Comparing the discharges of the same fastigial neurons recorded before and during adaptation, this basic pattern did not change, but some parameters of the discharges did. The most consistent changes were in the latency of the burst for ipsiversive saccades, which was positively correlated with saccade size (1.28 ms/deg), and in the number of spikes associated with contraversive saccades, which was also positively correlated (0.55 spikes/deg). The former was more important when saccade size was decreasing, and the latter was more important when saccade size was increasing. Based on current knowledge of the anatomical connections of fastigial neurons, as well as on the effects of cerebellar lesions and on recordings in other structures, we argue that these changes are appropriate for causing the associated changes in saccade size.

Resets of torsional eye position errors in different lighting conditions

To investigate a resetting mechanism of torsional eye position errors, spontaneous scanning eye movements and visually guided eye movements in different lighting conditions were recorded three dimensionally. Two monkeys ( Macaca fuscata, TS, MI) were engaged in this experiment. A dual scleral search coil method was used for three-dimensional (3-D) eye movement recordings. In complete darkness, the thickness of Listing's plane at the onset of spontaneous saccades (0.51/0.37° (TS/MI)) and that at the end of spontaneous fixation periods (0.47/0.34° (TS/MI)) were significantly ( P<0.001) smaller than that at the end of spontaneous saccades (0.59/0.45° (TS/MI)) and that at the onset of spontaneous fixation periods (0.58/0.44° (TS/MI)). Such differences in the thickness of Listing's plane were not observed in the light ( P>0.10). Amplitude of torsional drift during post-saccadic fixation period was correlated with the amount of torsional position error at the end of saccade ( P<0.001). The slope of regressed line in the dark or dim light (−0.40 to −0.50/−0.32 to −0.33 (TS/MI)) was steeper than that in the light (−0.04/−0.03 to −0.09 (TS/MI)). A resetting mechanism for torsional eye position errors during post-saccadic fixation periods is active in the dark but inactive in the light.

Activity in the parabigeminal nucleus during eye movements directed at moving and stationary targets.

The parabigeminal nucleus (PBN) is a small satellite of the superior colliculus located on the edge of the midbrain. To identify activity related to visuomotor behavior, we recorded from PBN cells in cats trained to fixate moving and stationary targets. Cats tracked moving targets primarily with small catch-up saccades, and for target speeds of 2-6 degrees /s, they did so with sufficient accuracy to keep targets within 2.5 degrees of the visual axis most of the time. During intersaccade intervals of such close-order tracking, PBN cells fired at rates related to retinal position error (RPE), the distance between the center of the retina and the saccade target. Each cell was characterized by a best direction of RPE. Most commonly, activity rose rapidly with increasing RPE, peaked at a small RPE within the area centralis, and dropped off gradually with increasing target distance. For some cells, the range over which activity was monotonically related to RPE was considerably larger, but because the PBN was not systematically sampled, the maximum range of RPE encoded is presently unknown. During saccades, activity began to change at about peak saccade velocity and then rapidly reached a level appropriate to the RPE achieved at saccade end. Most response fields were large, and stationary saccade targets presented anywhere within them evoked brisk responses that terminated abruptly on saccade offset. Spontaneous saccades in the dark had little effect on PBN activity. These data suggest that the PBN is an integral part of a midbrain circuit generating target location information.

Neural control of on-line guidance of hand reaching movements

Orienting one's gaze towards a peripheral target is usually composed of a hypometric primary saccade followed by a secondary 'corrective saccade' triggered automatically (without conscious perception) by the retinal error at the end of the primary saccade and characterised by a short latency. Due to visual suppression during the saccade, the artificial introduction of a random small target jump during that short period remains undetected and triggers after the end of the primary saccade a normal 'corrective saccade'. As a result this procedure simulates an error in the planning of the primary saccade. On the other hand optimum hand pointing (trade-off between movement time and accuracy) is considered classically to involve a natural parallel initiation of saccade and hand response based on a poor peripheral retinal location, and a further amendment of the hand motor response based on the retinal error provided by the simultaneous vision of target and hand during the movement home phase. To test the hypothesis that the retinal feedback at the end of the primary saccade is used to update the visual target position and amend the ongoing hand motor response, we developed a paradigm involving both an optimum hand pointing and an undetected random target perturbation during the orienting saccade. In order to show that the amendments were controlled by a loop comparing the perceived target location with the dynamic hand position signal, vision of the limb was removed at movement onset. Results showed that the movement was smoothly monitored on-line without additional time processing demands. This functional property of flexibility of the ongoing hand motor response, was generalized from movement extent to movement direction. The undetectability of the perturbation at a conscious level was not a prerequisite for motor flexibility, which was further shown to depend on a critical phase of the limb movement beyond which the latter was no longer amendable, even when the limb was visible. The hand pointing flexibility was further generalised from pointing to the more complex hand reaching and grasping process. It was shown that the flexibility of both the transport and the grasp components were closely coupled. A careful analysis of the data suggested the controlled variable to be the general posture of the upper limb, reaching Bernstein's intuitions about redundancy reduction in skeletomotor systems with degrees of freedom in excess. A kinematics study of the motor flexibility of reaching and grasping in a patient with a bilateral optic ataxia favoured the idea of a posterior parietal cortex involvement in the error processing underlying motor flexibility, reaching the same conclusions as other recent studies using either Positron Emission Tomography or Transcranial Magnetic Stimulation.

A hypothetical fixation system capable of extending foveation in congenital nystagmus.

The model was designed and implemented using the Simulink component of MATLAB (T he Math Works, Natick, MA). The model is of modular, hierarchical de­ sign. The SP subsystem is based on Robinson,2 chosen for its relative simplicity and ability to be induced into instability, yielding a sinusoidal oscillation characteristic of pendular nystagmus. The saccadic system was based around a resettable neural integrator 3,4 (RNI) with pulse-height and -width nonlinearities. The RNI is part of the circuit that determines saccade duration; when the RNI resets, the saccade ends. The 1M, which is the brains of the model, has a long history in ocular motor models. 3-8 The 1M makes use of visual signals from the retina, as well as position and velocity efference signals available in the brainstem, to reconstruct and properly respond to changes in target position and velocity. It can then use this information to coordinate interaction between the SP and saccadic and fixation subsystems, despite