Contrasting neuronal activity in the supplementary and frontal eye fields during temporal organization of multiple saccades

The organization of a series of actions into an appropriate temporal order is of particular importance in the voluntary control of motor behavior. Previous reports have emphasized the importance of medial motor areas for the temporal organization of movements. The aim of this study was to compare the neuronal activity in the supplementary and frontal eye fields (SEF and FEF) during sequential performance of multiple saccades to clarify the role of the two cortical oculomotor areas in the temporal organization of saccades based on memorized information. We analyzed neuronal activity while monkeys performed three saccades to peripheral targets in orders that were instructed and memorized. We found that activity that reflected saccade sequence or the numerical position of a saccade within a sequence (rank) was more prevalent in the SEF, whereas activity reflecting saccade direction was more dominant in the FEF. Furthermore, a sizeable number of SEF neurons exhibited an increase in activity when the animals were required to discard a current sequence and compose a novel sequence. We propose that the SEF is primarily involved in the process of planning, decoding, and updating saccade sequences, whereas the FEF plays a major role in determining the direction of forthcoming 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.     

Neuronal activity in macaque supplementary eye field during planning of saccades in response to pattern and spatial cues

The aim of this study was to determine whether neuronal activity in the macaque supplementary eye field (SEF) is influenced by the rule used for saccadic target selection. Two monkeys were trained to perform a variant of the memory-guided saccade task in which any of four visible dots (rightward, upward, leftward, and downward) could be the target. On each trial, the cue identifying the target was either a spot flashed in superimposition on the target (spatial condition) or a foveally presented digitized image associated with the target (pattern condition). Trials conforming to the two conditions were interleaved randomly. On recording from 439 SEF neurons, we found that two aspects of neuronal activity were influenced by the nature of the cue. 1) Activity reflecting the direction of the impending response developed more rapidly following spatial than following pattern cues. 2) Activity throughout the delay period tended to be higher following pattern than following spatial cues. We consider these findings in relation to the possible involvement of the SEF in processes underlying attention, arousal, response-selection, and motor preparation.     

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.     

Incomplete suppression of distractor-related activity in the frontal eye field results in curved saccades

Saccades in the presence of distractors show significant trajectory curvature. Based on previous work in the superior colliculus (SC), we speculated that curvature arises when a movement is initiated before competition between the target and distractor goals has been fully resolved. To test this hypothesis, we recorded frontal eye field (FEF) activity for curved and straight saccades in search. In contrast to the SC, activity in FEF is normally poorly correlated with saccade dynamics. However, the FEF, like the SC, is involved in target selection. Thus if curvature is caused by incomplete target selection, we expect to see its neural correlates in the FEF. We found that saccades that curve toward a distractor are accompanied by an increase in perisaccadic activity of FEF neurons coding the distractor location, and saccades that curve away are accompanied by a decrease in activity. In contrast, for FEF neurons coding the target location, there is no significant difference in activity between curved and straight saccades. To establish that the distractor-related activity is causally related to saccade curvature, we applied microstimulation to sites in the FEF before saccades to targets presented without distractors. The stimulation was subthreshold for evoking saccades and the temporal structure of the stimulation train resembled the activity recorded for curved saccades. The resulting movements curved toward the location coded by the stimulation site. These results support the idea that saccade curvature results from incomplete suppression of distractor-related activity during target selection.     

Neuronal activity related to visually guided saccades in the frontal eye fields of rhesus monkeys: comparison with supplementary eye fields.

1. The purpose of this study was to analyze the response properties of neurons in the frontal eye fields (FEF) of rhesus monkeys (Macaca mulatta) and to compare and contrast the various functional classes with those recorded in the supplementary eye fields (SEF) of the same animals performing the same go/no-go visual tracking task. Three hundred ten cells recorded in FEF provided the data for this investigation. 2. Visual cells in FEF responded to the stimuli that guided the eye movements. The visual cells in FEF responded with a slightly shorter latency and were more consistent and phasic in their activation than their counterparts in SEF. The receptive fields tended to emphasize the contralateral hemifield to the same extent as those observed in SEF visual cells. 3. Preparatory set cells began to discharge after the presentation of the target and ceased firing before the saccade, after the go/no-go cue was given. These neurons comprised a smaller proportion in FEF than in SEF. In contrast to their counterparts in SEF, the preparatory set cells in FEF did not respond preferentially in relation to contralateral movements, even though most responded preferentially for movements in one particular direction. The time course of the discharge of the FEF set cells was similar to that of their SEF counterparts, except that they reached their peak level of activation sooner. The few preparatory set cells in FEF tested with both auditory and visual stimuli tended to respond preferentially to the visual targets, whereas, in contrast, most set cells in SEF were bimodal. 4. Sensory-movement cells represented the largest population of cells recorded in FEF, responding in relation to both the presentation of the targets and the execution of the saccade. Although some of these sensory-movement cells resembled their counterparts in SEF by exhibiting a sustained elevation of activity, most of the FEF sensory-movement cells gave two discrete bursts, one after the presentation of the target and another before and during the saccade. Like their counterparts in SEF, the sensory-movement cells tended to be tuned for saccades into the contralateral hemifield, but this tendency was more pronounced in FEF than in SEF. The FEF sensory-movement cells discharged more briskly, with a shorter latency relative to the presentation of the target, than their counterparts in SEF. In addition, the FEF sensory-movement neurons reached their peak activation sooner than SEF sensory-movement neurons. Most FEF sensory-movement cells exhibited different patterns of activation in response to visual and auditory targets.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Neuronal activity related to rule and conflict in macaque supplementary eye field

Neuronal activity in macaque supplementary eye field (SEF) is enhanced during performance of the antisaccade task. This could be related to the selection of targets by a difficult rule (move to a location diametrically opposite the cue) or to conflict between the automatic tendency to look at the cue and the voluntary intention to look away. To distinguish between rule- and conflict-based mechanisms of enhancement, we monitored neuronal activity in the SEF during performance of a delayed response task in which monkeys selected saccade targets in response to peripheral visual cues. In spatial trials, the monkey had to select as target the location marked by the cue. In color trials, the monkey had to select as target the location associated with the color of the cue. 'Color-congruent' trials resembled spatial trials in that saccades were directed to the location occupied by the cue. Nevertheless, many SEF neurons were sensitive to the rule being used, with the majority firing more strongly under the color-rule condition. 'Color-incongruent' trials resembled 'color-congruent' trials in that a color rule guided target selection. Nevertheless, many SEF neurons were sensitive to the spatial relation between cue and saccade, with the majority firing more strongly on trials in which they were incongruent. We conclude that neuronal activity in the SEF is enhanced in connection both with the use of a more difficult rule and with conflict.     

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.     

Neuronal activity related to anticipated and elapsed time in macaque supplementary eye field

It is essential to sense anticipated and elapsed time in our daily life. Several areas of the brain including parietal cortex, prefrontal cortex, basal ganglia and olivo-cerebellar system are known to be related to this temporal processing. We now describe a number of cells in the supplementary eye field (SEF) with phasic, delay activity and postdelay activity modulation that varied with the length of the delay period. This variation occurred in two manners. First, cells became active with the shorter delay periods (GO signal presented earlier). We call these cells “short-delay cells”. Second, cells became active with the longer delay periods (GO signal presented later). We call these cells “long-delay cells”. However, such changed neuronal activity did not correlate with reaction time. These results suggest that the delay-dependent activity may reflect anticipated and elapsed time during performance of a delayed saccadic eye movement.     

Frontal eye field contributions to rapid corrective saccades

Visually guided movements can be inaccurate, especially if unexpected events occur while the movement is programmed. Often errors of gaze are corrected before external feedback can be processed. Evidence is presented from macaque monkey frontal eye field (FEF), a cortical area that selects visual targets, allocates attention, and programs saccadic eye movements, for a neural mechanism that can correct saccade errors before visual afferent or performance monitoring signals can register the error. Macaques performed visual search for a color singleton that unpredictably changed position in a circular array as in classic double-step experiments. Consequently, some saccades were directed in error to the original target location. These were followed frequently by unrewarded, corrective saccades to the final target location. We previously showed that visually responsive neurons represent the new target location even if gaze shifted errantly to the original target location. Now we show that the latency of corrective saccades is predicted by the timing of movement-related activity in the FEF. Preceding rapid corrective saccades, the movement-related activity of all neurons began before explicit error signals arise in the medial frontal cortex. The movement-related activity of many neurons began before visual feedback of the error was registered and that of a few neurons began before the error saccade was completed. Thus movement-related activity leading to rapid corrective saccades can be guided by an internal representation of the environment updated with a forward model of the error.     

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.     

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     

Properties of attentional selection during the preparation of sequential saccades

We examined the allocation of attention during the preparation of sequences of saccades in a dual task paradigm. As a primary task, participants performed a sequence of two or three saccades to targets arranged on a circular array. The secondary task was a two-alternative discrimination in which a critical discrimination stimulus (digital “E” or “3”) was presented among distractors either at one of the saccade goals or at any other position. The findings show that discrimination performance is enhanced at all the saccade target locations of the planned sequence, while it is close to chance level at the positions that are not relevant for the saccade sequence. An analysis of the discrimination performance at the intermediate locations indicates that saccade target selection involves spatially distinct, non-contiguous foci of attention. Further, our findings demonstrate that the movement-relevant locations are selected in parallel rather than serially in time. We conclude that during the preparation of a saccade sequence––well before the actual execution of the eye movement––attention is allocated in parallel to each of the individual movement targets.     

Activity in the supplementary motor area related to learning and performance during a sequential visuomotor task

Monkeys were trained in a serial reaction time task to produce hand movements according to changing locations of visual targets. In most trials, targets followed the same sequence repeatedly, whereas in other trials targets were presented in random locations or switched unpredictably between two alternative sequences. Single-unit activity was recorded from the caudal supplementary motor area (SMA-proper). Based on the activity associated with random movement sequences, effects of hand position and movement direction were evaluated. Activity was influenced by the hand position in ~60% of the neurons, and the movement direction influenced the activity of 51% of the neurons. In addition, 37 and 71% of SMA neurons displayed nonstationarity in their activity across successive movements within a given trial and across trials, respectively. Such nonstationarity in the ongoing neural activity and the effects of performance-related variables were evaluated using a regression model and separated from learning-related activity changes. About a third of SMA neurons displayed gradual changes in neural activity related to experience with a movement sequence across trials. Furthermore, about a quarter of SMA neurons showed similar changes within individual trials. When the individual movements included in the frequently repeated movement sequences were introduced unexpectedly, learning-related changes in neural activity were reduced, indicating that many SMA neurons changed their activity in relation to the learning of particular movement sequences. These results suggest that the pattern of neural activity in the cortical network involved in the control of movement sequences can be modified continuously by experience.     

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.