Neuronal correlates for preparatory set associated with pro-saccades and anti-saccades in the primate frontal eye field

Abstract

Diversity in behavioral responses to sensory stimuli has been attributed to variations in preparatory set. Variability in oculomotor responses toward identical visual stimuli has been well documented, but the neuronal processes underlying this variability are poorly understood. Here, we report evidence for set-related activity for saccadic eye movements in single neurons in the frontal eye field (FEF) in monkeys trained on a task in which they either had to look toward a visual stimulus (pro-saccade) or away from the stimulus (anti-saccade) depending on a previous instruction. A portion of FEF neurons were identified as neurons projecting directly to the superior colliculus (SC) with antidromic activation techniques. Saccade-related neurons in the FEF had lower prestimulus and stimulus-related activity on anti-saccade trials compared with pro-saccade trials. The level of prestimulus activity correlated with saccadic reaction times, express saccade occurrence, and errors in the anti-saccade task. In addition, saccade-related activity in the FEF was higher for pro-saccades than for anti-saccades. These results demonstrate that the direct descending pathway from the FEF to the SC carries preparatory set-related activity for pro-saccades and anti-saccades. The results also provide insights into the neuronal basis of variations in saccadic reaction times and in the control of the prepotent response to glance to a flashed stimulus.

Fig. 1.

Experimental configuration and antidromic responses. A, Lateral view of a rhesus monkey brain illustrating single-neuron recording in the FEF and stimulation of the ipsilateral SC. B, Antidromic response of an FEF neuron (arrow, top trace) and its collision with a spontaneously generated action potential (arrow, bottom trace) that triggered microstimulation. The vertical dashed line indicates the time of SC stimulation.C, Histogram of antidromic latencies for 33 identified corticotectal neurons. Hatched bars indicate saccade-related neurons.

Fig. 2.

Spatial and temporal representation of the behavioral paradigm. A, B, The monkey was required to look at a central FP for 700–900 msec. A red FP signaled a pro-saccade trial, and a green FP signaled an anti-saccade trial. On half of the trials, the FP disappeared 200 msec before the peripheral stimulus was presented (Gapcondition). On the other half of the trials, the FP remained illuminated throughout the trial (Overlap condition). A red stimulus was then presented pseudorandomly and with equal probability either in the response field of the neuron (dashed circle) or at the mirror position. On pro-saccade trials (A), the monkey was required to look toward the stimulus (red solid arrow), whereas he had to look to the mirror position (green solid arrow) on anti-saccade trials (B). Monkeys sometimes generated incorrect responses in the gap anti-saccade condition (red dashed arrow). E, Eye position;FP, fixation point; S, stimulus.C, Cumulative distribution of SRTs of all pro-saccades (red) and anti-saccades (green) in the gap (dashed lines) and overlap conditions (solid lines) obtained while recording from neurons in the FEF. The thick dotted red line represents incorrect responses in the gap anti-saccade condition. The mean SRT ± SD (and number of responses) in each condition was pro-gap, 164 ± 130 msec (n = 5303); pro-overlap, 239 ± 142 msec (n = 5210); anti-gap, 205 ± 111 msec (n = 4455); anti-overlap, 279 ± 122 msec (n = 4532); direction errors in the anti-gap, 179 ± 233 msec (n = 1482).

Fig. 3.

Activity of a corticotectal neuron (same as Fig.1B) recorded in the FEF during the pro-/anti-saccade paradigm. Activity in the left panelsis aligned on appearance of the eccentric stimulus (S on), and activity in the right panels is aligned on the beginning of the saccade (Saccade onset).A, Activity of the neuron on overlap trials when the stimulus was presented in its response field (RF, dashed circle) on pro-saccade trials (red) and anti-saccade trials (green). Eachdot indicates the time of an action potential, and eachrow represents one trial. The trials are sorted according to saccadic reaction times (indicated by vertical tickmarks). The bottom panel shows the average activation waveforms for pro-saccades (red, thick) and anti-saccades (green, thin).B, Same as in A but for stimulus presentations at the mirror position of the response field of the neuron. C, Same as in A but for the gap condition in which the FP disappeared 200 msec before stimulus appearance. D, Same as in C but for stimulus presentations at the mirror position of the response field of the neuron in the gap condition.

Fig. 4.

Activity during the instruction period. The mean discharge rate of individual neurons in the period 400–200 msec before stimulus presentation on pro-saccade trials is plotted against the mean activity on anti-saccade trials. Filled squares indicate antidromically activated corticotectal neurons. Dashed line is the unity line (slope, 1).

Fig. 5.

Prestimulus activity on overlap and gap trials.A, Mean spike density on pro-saccade trials (thick lines) and anti-saccade trials (thin lines) in the overlap (solid lines) and gap (dashed lines) conditions. B, The mean discharge rate of individual neurons in the period 40–50 msec after stimulus presentation (A, shaded region) on overlap pro trials (mean, 11.7 ± 1.1 spikes/sec) is plotted against the mean activity on gap pro trials (mean, 19.8 ± 1.6 spikes/sec).Filled squares indicate antidromically activated neurons. Dashed line is the unity line (slope, 1).C, Same as in B but for the comparison of anti-saccades between the gap (mean, 15.7 ± 1.1 spikes/sec) and overlap condition (mean, 9.0 ± 1.4 spikes/sec). D,Same as in B but for the comparison between pro- and anti-saccades in the gap condition.

Fig. 6.

Relationship between neuronal activity and saccadic reaction times in the gap condition. A, Mean correlation coefficients between neuronal activity and saccadic reaction times in 10 msec bins from 200 msec before to 100 msec after stimulus presentation for pro-saccades (thick lines) and anti-saccades (thin lines) in the response field of the neuron (solid lines) and to opposite position (dashed lines). B, C, Distribution of correlation coefficients between the mean activity from 40–50 msec after stimulus presentation (A, shaded area) and saccadic reaction time for pro-saccades and anti-saccades, respectively. The filled bars represent neurons with statistically significant correlations (p < 0.05).

Fig. 7.

Neural activity for express and regular saccades in the gap pro-saccade condition. A, Activity of a FEF neuron aligned on the presentation of the visual stimulus. Eachdot indicates the time of an action potential relative to stimulus presentation, and each row represents one trial. The trials are sorted according to saccadic reaction times (indicated by vertical tickmarks). The bottom panel shows the average activation waveforms for express (thick) and regular (thin) saccades.B, Same as in A but aligned on the beginning of the saccade. C, Mean spike density of the sample of FEF neurons on express saccade trials (thick line) and regular saccade trials (thin line) for saccades into the response field of the neurons. D,Activity levels in the time 40–50 msec after stimulus presentation (B, shaded area) are plotted before express saccades (mean, 30.6 ± 5.7 spikes/sec) against the activity levels before regular saccades (mean, 20.8 ± 3.9 spikes/sec). Theoblique dashed line represents the unity line (slope, 1). Filled squares indicate antidromically activated neurons.

Fig. 8.

Comparison of saccade-related activity on express and regular saccade trials. A, Mean spike density of the sample of neurons on express saccade trials (thick line) and regular saccade trials (thin line) for saccades into the response field of the neurons. B, The pre-saccade activity in the interval 20–10 msec before saccade onset (A, hatched area) of individual neurons on express saccade trials (mean, 48.0 ± 7.7 spikes/sec) is plotted against the pre-saccade activity on regular saccade trials (mean, 56.8 ± 10.9 spikes/sec). The oblique dashed line represents the unity line (slope, 1). Filled squares indicate antidromically activated neurons. C, The saccade activity (A, shaded area) of individual neurons on express saccade trials (mean, 97.1 ± 16.9 spikes/sec) is plotted against the saccade activity on regular saccade trials (mean, 98.2 ± 19.4 spikes/sec).

Fig. 9.

Activity on correct and error anti-saccade trials.A, Activity of an antidromically activated corticotectal neuron on correct trials (solid line) and error trials (dashed line) for stimulus presentations in the response field of the neuron (dashed circle). B,Mean spike density of the sample of FEF neurons on correct trials (thin solid line) and error trials (thick dashed line) for stimulus presentations into the response field of the neurons. C, Activity levels in the time 40–50 msec after stimulus presentation (B, shaded area) are plotted before correct anti-saccades (mean, 16.7 ± 1.9 spikes/sec) against the activity levels before errors (mean, 22.4 ± 2.3 spikes/sec). The oblique dashed line represents the unity line (slope, 1). Filled squares indicate antidromically activated neurons. D, Same as inC but for correct anti-saccades (mean, 18.2 ± 2.9 spikes/sec) and errors (mean, 13.8 ± 2.5 spikes/sec) for stimulus presentations at the mirror position.

Fig. 10.

Stimulus-related activity. A, Mean spike density of the sample of visuomovement neurons on pro-saccade trials (thick line) and anti-saccade trials (thin line) for stimulus presentations into the response field of the neurons. B, The prestimulus activity (A, hatched areas) of individual neurons on pro-saccade trials is plotted against the prestimulus-related activity on anti-saccade trials.C, The stimulus-related activity (A, shaded area) of individual neurons on pro-saccade trials is plotted against the stimulus-related activity on anti-saccade trials after subtracting the prestimulus level of activity (A, hatched area). The oblique dashed lines represent the unity line (slope, 1). Filled squares indicate antidromically activated neurons.

Fig. 11.

Saccade-related activity. A, Mean spike density of the sample of neurons on pro-saccade trials (thick line) and anti-saccade trials (thin line) for saccades into the response field of the neurons.B, The pre-saccade activity in the interval 20–10 msec before saccade onset (A, hatched area) of individual neurons on pro-saccade trials is plotted against the pre-saccade activity on anti-saccade. The oblique dashed linerepresents the unity line (slope, 1). Filled squaresindicate antidromically activated neurons. C, The saccade activity (A, shaded area) of individual neurons on pro-saccade trials is plotted against the saccade activity on anti-saccade trials.