Combination of neuronal signals representing object-centered location and saccade direction in macaque supplementary eye field

Neurons in the macaque supplementary eye field (SEF) fire at different rates in conjunction with planning saccades in different directions. They also exhibit object-centered spatial selectivity, firing at different rates when the target of the saccade is at the left or right end of a horizontal bar. To compare the rate of incidence of the two kinds of signal, and to determine how they combine, we recorded from SEF neurons while monkeys performed a task in which the target (a dot or the left or right end of a horizontal bar) could appear in any visual field quadrant. During the period when the target was visible on the screen and the monkey was preparing to make a saccade, many neurons exhibited selectivity for saccade direction, firing at a rate determined by the direction of the impending saccade irrespective of whether the target was a dot or the end of a bar. On bar trials, many of the same neurons exhibited object-centered selectivity, firing more strongly when the target was at the preferred end of the bar regardless of saccade direction. The rate of incidence of object-centered selectivity (33%) was lower overall than that of saccade-direction selectivity (56%). Signals related to saccade direction and the object-centered location of the target tended to combine additively. The results suggest that the SEF is at a transitional stage between representing the object-centered command and specifying the parameters of the saccade.     

Relationship of presaccadic activity in frontal eye field and supplementary eye field to saccade initiation in macaque: Poisson spike train analysis

The purpose of this study was to investigate the temporal relationship between presaccadic neuronal discharges in the frontal eye fields (FEF) and supplementary eye fields (SEF) and the initiation of saccadic eye movements in macaque. We utilized an analytical technique that could reliably identify periods of neuronal modulation in individual spike trains. By comparing the observed activity of neurons with the random Poisson distribution generated from the mean discharge rate during the trial period, the period during which neural activity was significantly elevated with a predetermined confidence level was identified in each spike train. In certain neurons, bursts of action potentials were identified by determining the period in each spike train in which the activation deviated most from the expected Poisson distribution. Using this method, we related these defined periods of modulation to saccade initiation in specific cell types recorded in FEF and SEF. Cells were recorded in SEF while monkeys made saccades to targets presented alone. Cells were recorded in FEF while monkeys made saccades to targets presented alone or with surrounding distractors. There were no significant differences in the time-course of activity of the population of FEF presaccadic movement cells prior to saccades generated to singly presented or distractor-embedded targets. The discharge of presaccadic movement cells in FEF and SEF could be subdivided quantitatively into an early prelude followed by a high-rate burst of activity that occurred at a consistent interval before saccade initiation. The time of burst onset relative to saccade onset in SEF presaccadic movement cells was earlier and more variable than in FEF presaccadic movement cells. The termination of activity of another population of SEF neurons, known as preparatory set cells, was time-locked to saccade initiation. In addition, the cessation of SEF preparatory set cell activity coincided precisely with the beginning of the burst of SEF presaccadic movement cells. This finding raises the possibility that SEF preparatory set cells may be involved in saccade initiation by regulating the activation of SEF presaccadic movement cells. These results demonstrate the utility of the Poisson spike train analysis to relate periods of neuronal modulation to behavior.     

Evidence for a supplementary eye field

Electrical microstimulation and unit recording were performed in dorsomedial frontal cortex of four alert monkeys to identify an oculomotor area whose existence had been postulated rostral to the supplementary motor area. Contraversive saccades were evoked from 129 sites by stimulation. Threshold currents were lower than 20 microA in half the tests. Response latencies were usually longer than 50 ms (minimum: 30 ms). Eye movements were occasionally accompanied by blinks, ear, or neck movements. The cortical area yielding these movements was at the superior edge of the frontal lobe just rostral to the region from which limb movements could be elicited. Depending on the site of stimulation, saccades varied between two extremes: from having rather uniform direction and size, to converging toward a goal defined in space. The transition between these extremes was gradual with no evidence that these two types were fundamentally different. From surface to depth of cortex, direction and amplitude of evoked saccades were similar or changed progressively. No clear systematization was found depending on location along rostrocaudal or mediolateral axes of the cortex. The dorsomedial oculomotor area mapped was approximately 7 mm long and 6 mm wide. Combined eye and head movements were elicited from one of ten sites stimulated when the head was unrestrained. In the other nine cases, saccades were not accompanied by head rotation, even when higher currents or longer stimulus trains were applied. Presaccadic unit activity was recorded from 62 cells. Each of these cells had a preferred direction that corresponded to the direction of the movement evoked by local microstimulation. Presaccadic activity occurred with self-initiated as well as visually triggered saccades. It often led self-initiated saccades by more than 300 ms. Recordings made with the head free showed that the firing could not be interpreted as due to attempted head movements. Many dorsomedial cortical neurons responded to photic stimuli, either phasically or tonically. Sustained responses (activation or inhibition) were observed during target fixation. Twenty-one presaccadic units showed tonic changes of activity with fixation. Justification is given for considering the cortical area studied as a supplementary eye field. It shares many common properties with the arcuate frontal eye field. Differences noted in this study include: longer latency of response to electrical stimulation, possibility to evoke saccades converging apparently toward a goal, and long-lead unit activity with spontaneous saccades.     

Executive control of countermanding saccades by the supplementary eye field

The supplementary eye field registers the occurrence of conflict, errors and reward in macaque monkeys performing a saccade-countermanding task. Using intracortical microstimulation, we determined whether the supplementary eye field only monitors or can actually influence performance. Weak microstimulation of many sites in the supplementary eye field improved monkeys' performance on a 'stop signal' task by delaying saccade initiation. This effect depended on the context of the task because simple visually guided saccades were not delayed by the same stimulation. These results demonstrate that the supplementary eye field can exert contextual executive control over saccade generation.     

The frontal eye field provides the goal of saccadic eye movement

Summary Microstimulation of oculomotor regions in primate cortex normally evokes saccadic eye movements of stereotypic directions and amplitudes. The fixed-vector nature of the evoked movements is compatible with the creation of either an artificial retinal or motor error signal. However, when microstimulation is applied during an ongoing natural saccade, the starting eye position of the evoked movement differs from the eye position at stimulation onset (due to the latency of the evoked saccade). An analysis of the effect of this eye position discrepancy on the trajectory of the eventual evoked saccade can clarify the oculomotor role of the structure stimulated. The colliding saccade paradigm of microstimulation was used in the present study to investigate the type of signals conveyed by visual, visuomovement, and movement unit activities in the primate frontal eye field. Colliding saccades elicited from all sites were found to compensate for the portion of the initial movement occurring between stimulation and evoked movement onset, plus a portion of the initial movement occurring before stimulation. This finding suggests that activity in the frontal eye field encodes a retinotopic goal that is converted by a downstream structure into the vector of the eventual saccade. Offprint requests to: J. Schlag, Department of Anatomy and Cell Biology     

Interaction of the frontal eye field and superior colliculus for saccade generation

Both the frontal eye field (FEF) in the prefrontal cortex and the superior colliculus (SC) on the roof of the midbrain participate in the generation of rapid or saccadic eye movements and both have projections to the premotor circuits of the brain stem where saccades are ultimately generated. In the present experiments, we tested the contributions of the pathway from the FEF to the premotor circuitry in the brain stem that bypasses the SC. We assayed the contribution of the FEF to saccade generation by evoking saccades with direct electrical stimulation of the FEF. To test the role of the SC in conveying information to the brain stem, we inactivated the SC, thereby removing the circuit through the SC to the brain stem, and leaving only the direct FEF-brain stem pathway. If the contributions of the direct pathway were substantial, removal of the SC should have minimal effect on the FEF stimulation, whereas if the FEF stimulation were dependent on the SC, removal of the SC should alter the effect of FEF stimulation. By acutely inactivating the SC, instead of ablating it, we were able to test the efficiency of the direct FEF-brain stem pathway before substantial compensatory mechanisms could mask the effect of removing the SC. We found two striking effects of SC inactivation. In the first, we stimulated the FEF at a site that evoked saccades with vectors that were very close to those evoked at the site of the SC inactivation, and with such optimal alignment, we found that SC inactivation eliminated the saccades evoked by FEF stimulation. The second effect was evident when the FEF evoked saccades were disparate from those evoked in the SC, and in this case we observed a shift in the direction of the evoked saccade that was consistent with the SC inactivation removing a component of a vector average. Together these observations lead to the conclusion that in the nonablated monkey the direct FEF-brain stem pathway is not functionally sufficient to generate accurate saccades in the absence of the indirect pathway that courses from the FEF through the SC to the brain stem circuitry. We suggest that the recovery of function following SC ablation that has been seen in previous studies must result not from the use of an already functioning parallel pathway but from neural plasticity within the saccadic system.     

Trajectory interpretation by supplementary eye field neurons during ocular baseball

Good performance in the sport of baseball shows that humans can determine the trajectory of a moving object and act on it under the constraint of a rule. We report here on neuronal activity in the supplementary eye field (SEF) of monkeys performing an eye movement task inspired by baseball. In "ocular baseball," a pursuit eye movement to a target is executed or withheld based on the target's trajectory. We found that a subset of neurons in the SEF interpreted the trajectory according to the task rule. Other neurons specified at a later time the command to pursue the target with the eyes. The results suggest that the SEF can interpret sensory signals about target motion in the context of a rule to guide voluntary eye movement initiation.     

Attention-related neurons in the supplementary eye field of the macaque monkey

This study investigated whether the neuronal activity of a cortical area involved in the control of eye fixation is affected by the covert orienting of attention. We recorded single-unit activity from the supplementary eye field (SEF) of two macaque monkeys performing fixation and peripheral-attention tasks. Ninety-nine out of four hundred and fifteen cells were related to eye movements. The other neurons showed relationship with postural adjustments, and arm and ear movements. Fifty-five neurons were active during fixation (fixation cells) and 44 discharged in relation to saccades. The experiments reported here primarily concern the fixation cells. The activity of 64% (35/55) of fixation cells started with the onset of visual stimulus, before the visual input reached the fovea, and continued during active fixation. The activity of 27% (15/55) of fixation cells started with the onset of fixation. The activity of 9% (5/55) of fixation cells modified their timing trial by trial. Sixty-four percent of the fixation cells (35/55) were position-dependent, showing a selective spatial field of activity, 36% (20/55) were position-independent and characterized by a full spatial field. None of the 55 cells showed a visual receptive field. We tested both types of fixation cells by means of a peripheral attention task. When attention was oriented peripherally toward a target located in the selective spatial field, the cells discharged as if the gaze was held toward it. When attention was oriented peripherally toward a target, lying outside the selective spatial field, the cells were inactive as if gaze was held in that position. These results suggest that the supplementary eye field neurons may code for oriented attention in space and might be involved in the preparation of motor action. Preliminary results were presented at the 1994 ENA meeting in abstract form     

Flexible interpretation of a decision rule by supplementary eye field neurons

Since the environment is in constant flux, decision-making capabilities of the brain must be rapid and flexible. Yet in sensory motion processing pathways of the primate brain where decision making has been extensively studied, the flexibility of neurons is limited by inherent selectivity to motion direction and speed. The supplementary eye field (SEF), an area involved in decision making on moving stimuli, is not strictly a sensory or motor structure, and hence may not suffer such limitations. Here we test whether neurons in the SEF can flexibly interpret the rule of a go/nogo task when the decision boundary in the task changes with each trial. The task rule specified that the animal pursue a moving target with its eyes if and when the target entered a visible zone. The size of the zone was changed from trial to trial in order to shift the decision boundary, and thereby assign different go/nogo significance to the same motion trajectories. Individual SEF neurons interpreted the rule appropriately, signaling go or nogo in compliance with the rule and not the direction of motion. The results provide the first evidence that individual neurons in frontal cortex can flexibly interpret a rule that governs the decision to act.     

Head movement evoked by electrical stimulation in the supplementary eye field of the rhesus monkey

Although the supplementary eye field (SEF) has been implicated in the control of head movements associated with gaze shifts, there is no direct evidence that SEF plays a role in the generation of head movements independent of gaze. If the SEF does, varying the duration of stimulation should selectively alter the head-movement kinematics during the postgaze-shift period. The duration of the stimulation was manipulated while head-unrestrained monkeys maintained stable head forward postures. The initial positions of the eyes in the orbits were systematically varied. Although combined movements of the eyes and head were produced in the majority of the trials, head movements were sometimes evoked in the absence of gaze shifts. These head-alone movements were most frequent when the initial eye position was contralateral to the stimulated side. When the stimulation produced eye and head movements, gaze onset was sometimes preceded by a relatively low-velocity phase of the head movement. Evoked head movements were primarily horizontal, unlike the gaze shifts, which typically had vertical components that varied according to the initial positions of the eyes in the orbits. The postgaze-shift head movements tended to be of low velocity and in many cases persisted until stimulation offset. In general, prolonging the stimulation resulted in improved centering of the eyes in the orbits. These findings suggest that, in addition to its previously described role in the generation of coordinated eye-head gaze shifts, the SEF is also involved in the control of head movements in the absence of a change of gaze.     

Reward-predicting and reward-detecting neuronal activity in the primate supplementary eye field

In addition to cells specifically active with visual stimuli, saccades, or fixation, the supplementary eye field contains cells that fire in precise temporal relationship with the occurrence of reward. We studied reward-related activity in two monkeys performing a prosaccade/antisaccade task and in one monkey trained in memory prosaccades only. Two types of neurons were distinguished by their reciprocal firing pattern: reward-predicting (RP) and reward-detecting (RD). RP neurons linearly increased their firing as early as 150 ms before saccade onset until the occurrence of reward, at which time they abruptly ceased firing. In contrast, RD neurons fired in phase with reward delivery, even when its duration was varied and when it was repeated at different frequencies. RD discharges were little affected or unaffected by the position of a visual cue that briefly anchored the goal at the onset of reward. The complementary firing patterns of the RP and RD neurons could provide a feedback mechanism necessary for learning and performing the task.     

Discharge of frontal eye field neurons during saccadic and following eye movements in unanesthetized monkeys

Summary The cortical mechanism of eye-movement control was investigated by recording single cell activity from the frontal eye field (FEF) in unanesthetized monkeys seated in a primate chair with head restrained. Two types of cells (I and II) were found. Type I neurons fired during voluntary saccades occurring in a given direction and during the fast phase of nystagmus. Cells of this type were silent during slow pursuit movement. Type II cells showed steady discharge when the eyes were oriented in a specific direction. These cells discharged also during smooth pursuit movements and the slow phase of nystagmus, provided that the eyes were moving across positions which would have been associated with neuronal activity had the eyes come to rest there. All of Type II and a few of Type I neurons were identified by antidromic response to stimulation of the cerebral peduncle. These results indicate that cortical neurons have patterns of discharge distinctly related either to saccadic or to pursuit movements, in line with the view that these two different types of eye movement are generated by distinct neuronal mechanisms.     

Chronometry of visual responses in frontal eye field, supplementary eye field, and anterior cingulate cortex

The latency and variability of latency of single-unit responses to identical visual stimulation were measured in the frontal eye field (FEF), supplementary eye field (SEF), and anterior cingulate cortex (ACC) of macaque monkeys performing visually guided saccades. The mean visual response latency was significantly shorter in FEF (64 ms) than in SEF (81 ms) or ACC (100 ms), and latency values determined by four methods agreed. The latency variability of the visual response was respectively less in FEF (21 ms) than in SEF (37 ms) or ACC (41 ms). Latency, variability of latency, and magnitude of the visual responses were correlated within FEF and SEF but not ACC. These characteristics of the visual response are consistent with the degree of convergence of visual afferents to these areas and constrain hypotheses about visual processing in the frontal lobe.