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JOURNALOFNEUROPHYSIOLOGY Vol. 58, No. 6, December 1987. Printed in U.S.A Functional Properties of Corticotectal Neurons in the Monkey’s Frontal Eye Field MARK A. SEGRAVES AND MICHAEL E. GOLDBERG Laboratory of SensorimotorResearch,National Eye Institute, National Institutes of Health, Bethesda,Maryland 20892 SUMMARY AND CONCLUSIONS 1. We examined the activity of identified corticotectal neurons in the frontal eye field of awake behaving rhesus monkeys (Macaca mulatta). Corticotectal neurons were antidromical y excited using biphasic cu rrent pulsespassedthrough monopolar microelectrodes within the superior colliculus. The activity of single corticotectal neurons was studied while the m.onkey performed behavioral tasks designed to test the relation of the neuron’s discharge to visual and oculomotor events. 2. Fifty-one frontal eye field corticotectal neurons were examined in two monkeys. Current thresholds for antidromic excitation ranged from 6 to 1,200 PA, with a mean of 330 PA. Antidromic latencies ranged from 1.2 to 6.0 ms, with a mean of 2.25 ms. 3. Fifty-three percent of the identified corticotectal neurons were classified as having movement-related activity. They had little or no responseto visual stimuli, but very strong activity before both visually guided and memory-guided saccades.An additional 6% of corticotectal n.eurons had v,isuomovement activity, combining both a visual- and a saccade-related response. In each case, visuomovement neurons antidromically excited from the superior colliculus had movement-related activity, which was much stronger than the visual component of their response. 4. Twenty-two percent of the corticotectal neurons were primarily responsive to visual stimulation of the fovea. These included both neurons responding to the onset and neurons responding to the disappearance of a light flashed on the fovea. 5. The remaining 20% of the corticotectal neurons were a heterogeneous group whose activity could not be classified as movement, visuomovement or foveal. Their responses included postsaccadic, anticipatory, and reward-related activity, as well as activity modulated during certain directions of smooth-pursuit eye movements. One neuron was unresponsive during all of the behavioral tasks used. There were no corticotectal neurons that could be classified as primarily responsive to peripheral visual stimuli. 6. Histological reconstructions of electrode penetrations localized corticotectal neurons to layer V of the frontal eye field. For 22 corticotectal neurons tested, each had its minimum threshold for antidromic excitation within the superior colliculus, as judged by either histological confirmation, or surrounding neuronal responsesrecorded through the stimulation microelectrode. The majority of these neurons had minimum threshold sites within the intermediate layers; a few minimum threshold sites were located within the superficial or deep collicular layers. 7. The lowest thresholds for antidromic excitation were obtained when the optimal saccade vectors associated with the frontal eye field recording and collicular stimulation sites were closely matched. There was a strong correlation between a measure of the difference between saccadesassociated with recording and stimulation sitesand the log of threshold for antidromic excitation. This relationship was such that small increases in the vector difference between frontal eye field and collicular saccadeswere accompanied by large increasesin threshold. 8. In comparison to the entire population 1387 1388 M. A. SEGRAVES AND of frontal eye field neurons examined by Bruce and Goldberg (7), we conclude that there is a selective enrichment within the population of corticotectal projection neurons for neurons with eye movement-related activity and neurons with fovea1 visual activity, and a paucity of neurons with peripheral visual receptive fields and postsaccadic activity. 9. These data suggest that the visual activity prevalent within the frontal eye field is likely to help generate the activity of movement-related neurons, but it is not a source for visual activity within the superior colliculus. 10. The frontal eye field’s projection to the superior colliculus provides several messages relevant for oculomotor performance, including information pertinent to the maintenance and release of fixation, and targeting information regarding an intended saccade. INTRODUCTION Since Ferrier’s original demonstration ( 12) that electrical stimulation of the monkey’s prearcuate frontal cortex produced conjugate eye movements, it has been postulated that this region participates in the voluntary control of gaze. However, a number of experiments have raised questions about the exact role of the frontal eye field in eyemovement control. This uncertainty results, in part, from the existence of parallel pathways that are likely to be involved in the input of eye movement control signals to the brain stem ocuomotor centers. The frontal eye field can affect the oculomotor system via three pathways (26, 33-35, 55). The first is by a direct projection to perioculomotor regions in the midbrain and pons (33). The second is by a projection to the caudate nucleus, which might then affect the inhibitory pathway from the substantia nigra pars reticulata to the superior colliculus (11, 24). The final one is a direct projection to the intermediate layers of the superior colliculus (1, 30). The relative contribution that each pathway makes to eye-movement control has not been determined. Additional problems arise when one considers the number of different neuron activity types that have been described in the frontal eye field. Bizzi (4) originally found that most frontal eye M. E. GOLDBERG field neurons were not related to spontaneous saccades made in the dark. The only neurons related to saccades were a small percentage (30/700) that became active only after the initiation of a saccadic eye movement. More recent single-neuron studies have indicated a role for the frontal eye field in the initiation of saccades. Mohler, Goldberg, and Wurtz (39) demonstrated that cells in the frontal eye field discharge in response to visual stimuli. This visual activity is enhanced when the monkey makes a saccade to the stimulus in the receptive field (62), and the enhancement only occurs before saccades and not before arm movements or other activity in which saccades do not occur (9). Bruce and Goldberg (7) recently reported that only - 19% of frontal eye field neurons have purely postsaccadic activity. The majority of neurons recorded from by Bruce and Goldberg in awake behaving monkeys had some form of activity that preceded visually guided saccadic eye movements, including a range of neuron activity from purely visual to purely movement related. It is clear there are signals in the frontal eye field that could drive saccadic eye movements and neural pathways by which these signals could reach brain stem oculomotor centers. However, to understand how the cerebral cortex controls a specific behavior, it is not sufficient to know the types of activity in the cortex and the anatomical projections of that region. One must also know what information is carried by the corticofugal signals. These output signals are likely to be produced bv a subset of the activity types within the entire neuronal population, and the output population will be enriched for some signal types and lacking others. To begin to answer this question, we identified corticotectal projection neurons by antidromic excitation from the superior colliculus and then characterized these neurons in awake behaving animals according to the scheme described by Bruce and Goldberg (7). A preliminary report of these experiments has been published elsewhere (5 3). METHODS Preoperative training Two adult rhesus monkeys (Macaca mulatta) were trained preoperatively to do a simple visual FRONTAL EYE FIELD CORTICOTECTAL fixation task using established techniques (60). The monkey was seated in a primate chair and began a trial by pressing a metal bar in front of him. This resulted in the onset of a target light on a screen in front of the monkey. The monkey was required to detect the dimming of the light and signal this detection by releasing the metal bar to receive a liquid reward. Surgery Surgery was performed under aseptic conditions. The monkey was anesthetized with ketamine hydrochloride (10 mg/kg im) followed by pentobarbital sodium through an intravenous catheter as needed. During the surgical procedure, a subconjunctival wire coil for the measurement of eye position with the magnetic search-coil technique was implanted in one eye (27,44). Trephine holes were made through the skull over the superior colliculi and over both left and right frontal eye fields. Stainless steel bolts to strengthen the bond of dental acrylic to the skull were fastened in slots cut through the skull and extending away from the edges of the trephine holes. Three recording cylinders, a steel receptacle to fix the monkey’s head during recording sessions, and the connector for the eye coil were fixed in place and bonded to the skull with dental acrylic. Immediately after surgery, the monkey was given gentamicin sulfate (5 mg/kg im) as a prophylactic measure against infection. The monkey received daily dosages of gentamicin sulfate for 1 wk postoperatively. Postoperative training was begun between 1.5 and 2 wk after surgery. Postoperative training After surgery, each monkey received additional training in several visual and saccade tasks. The computer hardware and software used to monitor and control the monkey’s behavior has recently been described in detail elsewhere (17). Briefly, the monkey was seated in a primate chair with its head fixed and centered within horizontal and vertical magnetic field coils. Visual stimuli presented to the monkey included stationary and movable light stimuli originating from yellow light-emitting diodes rear-projected onto a tangent screen 57 cm in front of the monkey. Each projected stimulus was -0.25’ in diameter with a brightness of 0.4 log units above a background of 1 cd/m*. The movable stimulus was positioned by a pair of servo-controlled mirror galvanometers (General Scanner, Watertown, MA) driven by analog signals synthesized by 12-bit digital-to-analog converters under the control of the computer. Since, after surgery, it was possible to accurately measure eye position, the monkey was no longer required to detect the dimming of the stimulus. Instead, the monkey had to meet predetermined NEURONS criteria for eye position relative to target position and for saccade amplitude and direction, in order to receive a liquid reward. Eye position was measured by the magnetic search-coil system using the C.N.C. Engineering phase-sensitive detector. Eye position measurement was accurate to 15 min of arc within a range of 20” from the center of gaze and was not corrected for cosine error. Each monkey was trained to do several behavioral tasks (Fig. 1). Each task began with the appearance of a central stationary light on the screen (Fig. 1, FP). The computer monitored the monkey’s eye position, and when the monkey had achieved fixation for 100 ms the computer then began the various timing intervals of each task: 1) FIXATION TASK (FIG. 1A). The monkey was required to hold fixation throughout the trial. During some trials the fixation light was turned off at an unpredictable moment for a brief period of time. The interval during which the light was turned off was the same in any given block of trials, but was varied from 200 to 500 ms between blocks of trials. The monkey was rewarded for maintaining eye position within a window surrounding the target such that the sum of the horizontal and vertical differences between eye and target position was ~5” (54). This was a criterion that the monkeys met easily, and usually surpassed. With practice each monkey was able to maintain fixation of the target’s initial position throughout the trial, including periods when the light was turned off. This paradigm enabled us to test the effects of visual stimulation of the fovea on neuronal activity. 2) VISUAL NO-SACCADE TASK (FIG. 1B). The monkey fixated the stationary light spot in the center of the tangent screen for the duration of the trial. During the trial, at an unpredictable time, a second light spot (Fig. lB, S) was flashed for a variable period of time. The position of the second light was controlled by mirror galvanometers and could be placed anywhere within the monkey’s visual field. The monkey was rewarded for maintaining fixation of the center light throughout the trial. The peripheral stimulus had no behavioral significance, but its position was used to map the visual receptive fields of frontal eye field neurons. 3) VISUALLY 1 C). After GUIDED SACCADE TASK (FIG. a variable period of fixation, the center light was extinguished at the same moment that a peripheral target light (Fig. 1, C and D, T) was turned on. When the peripheral target appeared, the monkey was required to make a saccade to it within 500 ms. After the saccade, the monkey was rewarded either for maintaining eye position within a window with -3-6’ radius surrounding the new target position or for having M. 1390 A. SEGRAVES AND M. E. GOLDBERG A Fixation VH L m-/ I B Visual No-Saccade VH 1 FP-I s I 1 C Visually Guided Saccade VH I IL FPJ T \ / D Memory Guided Saccade VH 10" \‘I / I FP-J T I L r 1 250 ms FIG. 1. Behavioral tasks. H, horizontal eye position; V, vertical eye position. An upward deflection signifies movement to the right for H and up for V. FP, fixation point; S, peripheral stimulus light; T, peripheral target light. For FP, S, and T, an upward deflection signifies light on. Each trial began when the monkey fixated a light in the center of the tangent screen and maintained fixation for at least 100 ms. A: fixation task. The sketch to the right of the eye position traces shows that only the fixation point appears in this task. During the trial, the fixation point was turned off for 200 ms. B: visual no-saccade task. Sketch at right indicates that both fixation point and stimulus flash occur in this task, but no saccade is made. C: visually guided saccade task. Sketch at right indicates that a saccade is made to the position of the target light after the fixation point is turned off. D: memory-guided saccade task. Sketch indicates that saccade is made to the remembered position of the target light after the disappearance of the fixation point. See text for an additional description of each task. made a saccade whose end point was within the window. The movable light spot was again used for the peripheral target and could be positioned anywhere on the tangent screen. In this task the simultaneous disappearance of the center fixation light and onset of peripheral target light were the cue for the monkey to make a saccade. 4) MEMORY-GUIDED 10). In a second SACCADE TASK (FIG. more difficult form of saccade task, the center light came on to start the trial, as before, and the monkey was required to begin and maintain fixation of the center light until it was turned off. During the central fixation period, a peripheral target was turned on for 50-300 ms. When the center light was turned off the monkey was required to make a saccade to the position of the flashed peripheral target light. The duration and time of occurrence of the target flash were adjusted so that the target light was turned off during the fixation period, requiring the monkey to maintain fixation for up to 250 ms after the target light’s disappearance and then make a sac- cade to a remembered target location. This task enabled us to distinguish between visual and movement associated neuronal activity during the trial. In this study, the location of visual stimuli and targets are expressed in polar coordinates, radius and angle, where radius is equal to the distance, in degrees of arc, of the target or stimulus from the central fixation point. An angle of 0” describes a rightward horizontal direction, and a 90” angle describes an upward vertical direction. Electrophysiology A diagram of the stimulation and recording setup is provided in Fig. 2, illustrating the antidromic excitation of a single neuron in the frontal eye field by a monopolar stimulating electrode in the superior colliculus. In these experiments, we defined the frontal eye field as the area of cortex, located primarily on the rostra1 bank of the arcuate sulcus, where eye movements can be evoked FRONTAL EYE FIELD CORTICOTECTAL NEURONS 1391 Stimulation Superior FIG. frontal Colliculus 2. Stim ulation and neuron eye field were antidromically recording configuration excited by a monopolar with thresholds of 50 PA or less (7, 8). Initial neuron recording in both the superior colliculus and the frontal eye field was done with glasscoated platinum-iridium electrodes (59) introduced through the intact dura. For the superior colliculi, penetrations through the dura were used to define the collicular topography relative to the recording cylinder. Once this topography was known, an M-gauge guide tube was introduced through the dura with the monkey under ketamine anesthesia (5- 10 mg/kg). The portion of the guide tube exposed above the dura was cemented to the wall of the recording cylinder with dental acrylic. The tip of the guide tube was positioned a few millimeters above the surface of the superior colliculus. This made it possible to make repeated penetrations with fine tungsten microelectrodes through the same region of the superior colliculus and reduced the amount of daily preparation time before the actual search for antidromically excitable neurons could begin. When the guide tube was not in use, a wire matched to the inside diameter of the 1&gauge tubing and coated with antibiotic (3% tetracycline HCl ointment) was inserted into it. In several instances, a single guide tube in the superior colliculus remained implanted for 1 mo without adverse effect. The tangential area of the superior colliculus sampled through the guide tube could be increased by slightly bending the electrode - 1 cm from its tip, resulting in the area “seen” by penetrations through the guide tube to be conical in shape. Neuronal recording in the frontal eye field was done both with platinum-iridium electrodes introduced through the dura and with tungsten electrodes passed through guide tubes. The use of guide tubes in the cortex made it easier to make Frontal . Eye Fields Single neurons isolated stimulating microelectrode by a in t icroelectrode in the superior collicul us. repeated penetrations through areas where antidromically excitable neurons were found previously and improved the recording stability. Twenty-seven (5 3%) of the antidromically excited and physiologically characterized neurons included in this report were recorded from electrodes passed through implanted guide tubes. Stimulation through the superior colliculus electrode to excite frontal eye field neurons antidromically was done with biphasic negative first pulses, with 0.2-ms pulse width. The output of the stimulus generator was connected to the electrode through constant-current optical isolators. The amount of stimulus current was determined from the voltage measured across a l-k0 resistor in series with the electrode. Searching for antidromitally excitable neurons was routinely done with stimulus currents of 1 .O mA. Once an antidromitally excitable neuron was isolated, its excitation threshold was determined and the stimulus current was then set to an amount -50% greater than threshold. We defined threshold as the current intensity at which antidromic spikes were obtained in response to -50% of the stimulus pulses. Single-shock stimulation never appeared to have any effect on the monkey; no eye or skeletal movement were ever evoked, nor did the monkey ever display a behavior that could be interpreted as resulting from an aversive stimulus. In fact, the monkey frequently fell asleep during the interval between behavioral trials when the superior colliculus stimulus was administered. Antidromically excited neuronal responses were identified by their fixed latency and by our ability to collide the neuronal spike with spontaneous spikes originating in the frontal eye field (3, 16). The amplified electrode signal was sampled at 12 1 1392 M. A. SEGRAVES AND kHz by an analog-to-digital converter and saved in computer memory. One sampling of the signal from the electrode lasted for 8.5 ms and was triggered by either the onset of the collicular stimulus or the beginning of a spontaneous neuronal spike in the frontal eye field. The digitized electrode signal trace was displayed on an oscilloscope and could be averaged with successive traces following the same trigger. Single and averaged traces were saved by the computer for future analysis and display. Figure 3 shows examples of antidromic excitation (Fig. 3, A and C) and collision (Fig. 3, B and 0). Two smaller neuronal spikes, driven by the collicular stimulus but not collidable by the larger neuron spike, are indicated by arrows in Fig. 3, C and D. Trains of pulses were occasionally applied at a frequency of 330 Hz through the recording microelectrode, to establish that the electrode was located in the low-threshold frontal eye field or the intermediate layer of the superior colliculus. Trains of stimulation in the deeper colliculus, close to the central gray occasionally evoked stereotyped skeletal movements, or, more rarely, aversive reactions. In the latter cases train stimulation was stopped and the electrode elevated to a nonaversive site. Train durations of 70 ms were used to evoke saccades, and durations >300 ms were used to evoke smooth pursuit (8). We searched for frontal eye field corticotectal neurons in two different ways. We obtained the highest yield of antidromically excitable neurons by stimulating at 50- to loo-pm intervals along a penetration through cortex, testing the activity of a neuron during behavioral tasks only when it had been identified as a corticotectal neuron. Alternatively, we made penetrations through the cortex and tested the activity of isolated neurons during the various behavioral tasks and then stimulated the colliculus to see if the neuron could be excited antidromically. The latter method was used to make sure that our electrode penetrations sampled all of the neuron types previously identified in the frontal eye field (7). Behavioral and neuronal activity were sampled at 1 kHz. Rasters and histograms were constructed with bin widths of 4 ms (250 Hz) on-line from this I-kHz sampled data and were then stored on magnetic disk for off-line analysis. Because the original I-kHz data was resampled at 250 Hz, minor quantization differences occurred between pairs of rasters and histograms constructed from the same original data set but with a fixed relative offset, for example beginning and end of a target flash. Since the precise positioning of sampling bins would not necessarily be the same for two different pairs of rasters and histograms, a given spike could fall in one bin on one raster and in an adjacent bin in the other raster. M. E. GOLDBERG c A B C * U A 1 ms * A A FIG. 3. Example of antidromic excitation, collision. Each trace begins with the occurrence of a spontaneous spike generated by a neuron isolated in the frontal eye field. Traces are aligned upon the superior colliculus stimulus artifact. A and B: single traces 8.5 ms in duration digitized by a high-speed analog-to-digital converter (see METHODS); C and D: averages of 10 consecutive traces. In A, 1 marks the spontaneous neuronal spike; 2, the superior colliculus stimulus artifact; and 3, the antidromically excited neuronal spike. When the spontaneous spike and superior colliculus stimulation were separated by 2.5 ms (A and C), the isolated neuron was excited antidromically with a latency of 1.5 ms. However, when the separation between spontaneous spike and stimulus was reduced to 0.6 ms, the antidromically evoked spike collided with the spontaneous spike and was not seen at the frontal eye field electrode (B and D). Note that two smaller neuron spikes evoked at constant latencies of 2.0 and 4.6 ms (arrow in C and D) were not affected. Time between ticks in lowest trace was 1 ms. Stimulus intensity, 50 PA. Furthermore, two spikes falling in one bin were treated as one spike, and thus a pair of spikes with frequency ~250 Hz could fall in one bin and count as a single spike in one raster, or fall in adjacent bins and count as two spikes in another raster. This effect is evident in the histograms of Figs. 8, B and C’, 10, -4 and B, and 11, B and C. These minor differences had absolutely no influence upon the classification of the firing activity of these units. FRONTAL EYE FIELD CORTICOTECTAL Data analysis NEURON CLASSIFICATION. The behavioral tasks described above were used to classify neurons according to the schema proposed by Bruce and Goldberg (7). The largest class of neurons in the frontal eye field are presaccadic neurons, which discharge before a visually guided eye movement. Presaccadic neurons are classified as visual, movement, or visuomovement. VC2& Y~~URVZSrespond to peripheral visual stimuli whether or not the monkey actually uses the stimulus as the target for a saccade. The response of a visual neuron may be enhanced when the monkey does make a saccade to the visual target, but the neuron does not fire when the monkey makes the identical eye movement in a learned saccade task in which the target light is not presented. Movement neuronshave little or no response to visual stimuli, but very strong activity before both visually guided and memory-guided saccades. Movement neurons have definable movement fields, but give little or no discharge before spontaneous saccades, of the appropriate direction, made in the dark. They do not discharge in response to visual stimulation of the fovea. Visuomovementneuronsshow both visual and movement-related activity, but their optimal discharge occurs before visually guided saccades, which distinguishes them from movement neurons whose activity is similar before both visually and memory-guided saccades. The visuomovement neurons occupy a continuum from strongly visual neurons with weak movement discharge to strongly movement neurons with weak visual activity. All presaccadic neurons can have anticipatory activity, beginning their discharge before the signal to make a saccade in paradigms where the monkey expects to make a saccade of a certain amplitude and direction. There are a number of neurons that cannot be classified as presaccadic. Two types are of interest to this study: fovea1 neurons and postsaccadic neurons. Fovea/ neuronsrespond to visual stimulation of the fovea and include neurons with on or off responses to fovea1 stimulation. We found uncomplicated foveal neurons that could only be driven by fovea1 stimuli and complex fovea1 neurons whose fovea1 responses were combined with visual, visuomovement, or movement anticipatory activity. Postsaccadicneuronsbegin to discharge during and after saccades, but not before. Histology Marking lesions were made at the site of an antidromically excited neuron in each hemisphere and at the lowest threshold collicular sites from which these neurons could be antidromitally excited. At the conclusion of the experiment, the monkeys were given a lethal dose of pento- NEURONS 1393 barbital sodium and were perfused transcardially with saline followed by 10% formalin. The brains were then removed, photographed, and frozen sectioned at 48 pm. Two planes of section were used. Sections through the superior colliculus were made in the coronal/frontal plane. Sections through the arcuate sulcus were made in a plane running rostrocaudally, parallel to the principal sulcus (see Fig. 5). Every 10th section was mounted and stained with cresyl violet. Additional sections were stained as needed. RESULTS Physiological antidromically classzj?cation of. excited neurons We physiologically characterized 5 1 antidromically excited neurons. Twenty-four neurons were recorded from the left frontal eye field of monkey M30, and 22 neurons from the right and 5 neurons from the left frontal eye field of monkey IM50. Table 1 shows the number and percentage of corticotectal neurons in each category of neuronal activity. LMOVEMENT NEURONS. Fifty-three percent of the corticotectal neurons (27 neurons) identified and characterized in this study belonged to the movement category. Figure 4 shows the activity, recorded during the memory-guided saccade task (Fig. 1D), from a movement neuron antidromically excited from the superior colliculus. The neuron did not discharge in response to the appearance of the target flash (Fig. 4A) but discharged briskly before the saccade (Fig. 4B), with a burst starting - 160 ms before, 1. Distribution neurons antidromically the superior colliculus TABLE Monkey Activity Type Visual Visuomovement Movement Postsaccadic Fovea1 Others Nonresponsive Totals See METHODS M30 ofactivity typesjtir excited from Monkey hf.50 Total Percent 0 0.0 12 3 27 2 4 9 11 5.9 52.9 2.0 21.6 15.7 2.0 24 27 3 1.5 for description 8 of neuron 51 activity 100.1 categories. M. 1394 A. SEGRAVES AND A M. E. GOLDBERG B Frontal Hvv Eye Field / r loo FP L p1 f T H vv FP ‘-1 T1 1 ..... .--. ... . . . . w . ... . ... ..... . . . . . . . . . . . . ... . .s- . . .. . . ..... . , -. ..... . ... . . . W” . ..... .... . . ” ... ..... . ... . . ... . . . . . .“_ . ..e . . .. ... . ......... .” . . I. . .. ..-. ............... . ....... .I . . . . . .. . .... ....... . "S. -.a- ._.” ... . . ..-w. . . .... . . ....... ... . . ... ..” . . w . . ... ..“. ... ......... . ..- . . . . .w . ..s .” . . ..“. .” . . ... .m -.- .. .... .... ..-. .-- ..... . . ..” ...... . . .. ... “M. . . . .... ..-.s . . ....... . ... . .. WV . .-.- . . .w ... .-. . .. . . ...... .. ..e- . s . ..-.s. .I ... ....... . B-.-w . . . . ..q ..“-. . . .. ..-. . ..... m ..... .... .- ...... w-..- . Activity . .... . . .. *- .. -. “W . .... , . ... I. ; . . . . ...... ... ’ .: . 200 ms/div C D Superior vv FP T 1 Activity Hv\ loo I I1 Colliculus 1 11 I FP T1 1 I I I I I I ~-1 I I I I I I I I 200 ms/div FIG. 4. Activity of a frontal eye field movement neuron antidromically excited from the superior colliculus (A, B) and multineuron activity recorded at the collicular stimulation site with lowest threshold for antidromic excitation of the frontal eye field neuron (C, D). Activity was obtained during performance of the memory-guided saccade task (Fig. lD), and each pair of illustrations compares activity synchronized on the appearance of the target (A, C) with activity synchronized on the beginning of the saccade (B, D). Each portion of this figure includes a raster, histogram, and sample eye movement traces for the paradigm employed. Each raster dot represents one neuron spike (sampled at 250 Hz), every raster line includes the neuron activity from a 2-s interval of a single trial. Each histogram is the summation of the raster illustrated above it with 4-ms bin width. The calibration mark to the left of each histogram FRONTAL EYE FIELD CORTICOTECTAL and peaking at the beginning of the saccade. The center of the movement field for this neuron was 5’ from the fixation point in the lower right quadrant (5” radius, 308’ angle in polar coordinates). The latency for antidromic excitation from the superior colliculus was 1.4 ms. An antidromic excitation threshold of 110 PA was first recorded for this neuron while stimulating from a depth within the superior colliculus where purely visual activity was recorded prior to stimulation. However, the minimum threshold for this neuron was obtained when the stimulating electrode was lowered 1 mm deeper into the superior colliculus. At this depth, the antidromic excitation threshold was 70 PA. The threshold for excitation increased as the electrode was advanced further, reaching a level of 115 PA at a depth of 1.5 mm below the initial stimulation site. Multiunit activity recorded at the superior colliculus stimulation site with lowest threshold showed a preponderance of activity surrounding the beginning of the eye movement, with only a slight visual response as is shown in Fig. 4, C and D. The center of the movement field for this multiunit activity was of greater amplitude, but in roughly the same direction into the lower right quadrant ( 11 O radius, 328’ angle). The lesions marking the recording site for this neuron in the frontal eye field, as well as the stimulation site with lowest threshold in the superior colliculus are illustrated in Fig. 5. The lesion marking the location of the corticotectal neuron was within cortical layer V. The site of lowest threshold for antidromic excitation was within the intermediate gray layer of the superior colliculus. 2. VISUOMOVEMENT NEURONS. we anti- dromically excited three visuomovement neurons (5.9%), one of which is shown in Fig. 6. In the memory-guided saccade task, this neuron had a weak visual response (Fig. 6A) followed by much stronger activity associated with the eye movement (Fig. 6B). Note that for this task, the beginning of the visual response and movement activity are FIG. 4, cont. NEURONS 1395 separated in time by ~750 ms. The activity of this neuron in the visually guided saccade task is shown in Fig. 6, C and D. Note the brisker response for the visually guided saccade, in which both the movement and the visual components occur simultaneously. The latency for antidromic excitation of this neuron was 1.2 ms. The minimum current threshold for excitation was 160 PA. Figure 7 shows photomicrographs of the recording and stimulation sites for this neuron. As was the case for the movement neuron described above, the recording site was localized to cortical layer V, and the stimulation site with lowest current threshold was within the intermediate gray layer of the superior colliculus. Neurons with visuomovement activity occurred infrequently in our sample of frontal eye field corticotectal neurons (3 neurons, 5.9%). Each of the other identified visuomovement neurons had activity that resembled that shown in Fig. 6 with a weak visual response overshadowed by strong movement activity. The activity preceding saccades for both visuomovement and movement corticotectal neurons occurred before both visually guided and memory-guided saccades. 3. FOVEAL NEURONS. Eleven neurons (21.6%) responded to visual stimulation of the retinal fovea. Fovea1 neurons included six neurons that exhibited a relatively uncomplicated response to either the onset or disappearance of a fovea1 stimulus. The remaining five neurons exhibited fovea1 responses in combination with activity that was anticipatory, evoked by peripheral visual stimuli, or related to some other behavioral or environmental parameter. The response of a foveal-on neuron is illustrated in Fig. 8. This neuron increased its firing rate immediately after the appearance of the central fixation light at the start of the trial (Fig. 8A) in the fixation task. Its activity level decreased during the time when the fixation light was turned off during the trial (Fig. 8B) and was reactivated following the reappearance of the light (Fig. 8C). Figure 9 shows the activity of represents a firing rate of 100 spikes/s. The vertical line passing through both raster and histogram is the point of alignment for the activity. The abbreviations and conventions for the eye movement and stimulus traces at the top of each raster are identical to those of Fig. 1. 1396 M. A. SEGRAVES AND M. E. GOLDBERG anterior ran B .i-3 ‘i a cm FIG. 5. Recording and stimulation sites for the same corticotectal neuron illustrated in Fig. 4. A: recording site for antidromically excited neuron marked by a lesion in cortical layer V in the fundus of the arcuate sulcus--blackened in drawing of section through arcuate sulcus, and indicated by white arrowhead in photomicrograph of same section. Cortical sections were made in a plane that was roughly parallel to that of the principal sulcus. The neuron was located in the left frontal eye field, and the cortical sections are oriented so that anterior is to the left, posterior to the right. In the section drawing, the shaded area on the anterior bank ofthe arcuate sulcus marks a region of necrotic tissue, probably resulting from the effects of previous penetrations. P.S.,principal sulcus; AS, arcuate sulcus. B: lesion marking stimulation site in the intermediate gray layer of the left superior colliculus. Coronal section. SGS, stratum griseum superticiale; SGI, stratum griseum intermediale; SGP, stratum griseum profundum. FRONTAL FP L T I . w . ,* . . . . ..s. . . . . . . . , . . . . . ..-m. . . . . . . . . . . . s-.--w * . . . _..L . IS . . . . . . . . . . . . m--w.” . . . . . . . . . . e . . . .. . . . . .. . . . . NEURONS 1397 . . . . . . . . e . ..“.-... . . . . .w-.-.m. . .-we-. . “.--.... ..w.-.-.- . . . . . .MLI.... . . . . . . . .e... m--m . . . , . . . . . . . . . . -. .M . CORTICOTECTAL FP 1 T . . FIELD L . w . EYE . . . . .* 200 ms/div C i f l loo FP [ FP - 200 ms/div 6. Corticotectal visuomovement neuron activity. A, B: activity during memory-guided saccade task. C, D: visually guided saccade task. Rasters and histograms aligned on the onset of the peripheral target in A and C and on the beginning of the saccadic eye movement in I? and D. Note that the visuomovement neuron has both visual activity, seen in the first burst in A and B, and movement activity, seen in the second burst in A and B. In Cand D the visual activity burst and the movement activity burst are superimposed, and the activity is greater than either of the bursts in A and II. The visual nature of the onset of the burst is illustrated by its excellent synchrony with the appearance of the target in C. The burst continues through the movement in each trial. FIG. M. A. SEGRAVES 1398 AND M. E. GOLDBERG As anterior posterior $jj - 3? 1 FIG. 7. Recording and stimulation sites for the corticotectal neuron illustrated in Fig. 6. Same conventions as used in Fig. 5. A: the lesion marking the recording site for this neuron was in layer V in the posterior bank of the arcuate sulcus near the fundus of the sulcus. B: the stimulation site was in the intermediate gray layer of the superior colliculus. a neuron that at first appeared to be movement related (Fig. 94. However, this activity occurred before saccades in every direction in the memory-guided saccade task and was, in fact, best interpreted as a visual response to the disappearance of the fixation light FRONTAL A EYE CORTICOTECTAL NEURONS B FP H V [ H V loo FP ,-I f II 1399 C H V I FIELD 1 III I III I I FP I I I I I I I I I I I 1 I I I I I I I I I I I 200 ms/div IG. 8. Corticotectal neuron with foveal-on response. Fixation the fixation light at the beginning of the trial. B: disappearance fixation. C: reappearance of the fixation light 500-ms later. (Fig. 9B). In the fixation task, this neuron became quiet when the fixation light was turned on at the beginning of the trial (Fig. 9C). It fired during the period when the fixation point was off in the middle of the trial (Fig. 90) and ceasedfiring -75 ms after the reappearance of the fixation point (Fig. 9E). It became active once more, 100 ms after the disappearance of the fixation point at the end of the trial (Fig. 9F). It should be noted that the activity of this neuron in the saccadetask is not fully explained by a foveal-off response, since the increase in firing rate actually occurs before the disappearance of the fixation light (Fig. 9B). This may represent activity that anticipates the impending eye movement. In the fixation task, where saccades are suppressed,the neuron’s firing rate did not increase until after the disappearance of the fixation light (Fig. 90). As mentioned above, about one-half (5/ 11) of the fovea1 corticotectal neurons exhibited more than a simple on or off response.The activity of one of these complex fovea1 neurons is illustrated in Fig. 10. In the fixation task, this neuron stopped firing when the fixation point was turned off during the trial (Fig. 1OA) and resumed firing in response to the reappearance of the fixation light (Fig. 1OB). However, its firing rate was affected by more than fovea1 visual stimulation alone. Figure 10, C and D, shows this neuron’s activity during a variation of the task. Rasters and of fixation light histograms aligned. A: while the monkey onset of maintained visually guided saccade task where the peripheral target light was continually present. The omnipresence of the peripheral target prevented it from evoking a phasic response from the neuron. The neuron was active while the monkey fixated the central fixation point, but it showed a suppressionof activity when the fixation point disappeared. This suppressionwas followed by a reactivation of the neuron’s activity coincident with the onset of the saccade that would attain the target, that is the future fixation point, in the periphery. Note that this increase in firing occurs before the target light is foveated. There did not appear to be a preferred target location associated with this activity. The neuron’s activity was linked to the fixation of a peripheral target light, rather than the retinotopic location of that target. Corticotectal fovea1 neurons did not appear to be localized to a particular portion of the topographic map of the frontal eye field. They were found in the vicinity of movement neurons with preferred saccadeamplitudes ranging from 6 to 30’. Likewise, the fovea1 neurons were antidromically excited from a wide range of points within the topographic representation in the superior colliculus. NEURONS. There was one neuron (2.0%) in our sample of corticotectal neurons classified as postmovement. 4. POSTMOVEMENT M. A. SEGRAVES 1400 FP; T1 FP FP 1 I T1 . .-. . . - .. ...... .... ... ..- .m .. .. ..... . ..... . ... .... . *.*I * . . . ..w . . ........ ..” . . . . . . ... .. w . . . ..... . . . . . . . -. .. ... -. . .-. . ..m . - . .. ... . .... ... -. ...... ...... - ... ... ..... . ... w.- ........ .. ........... ... .. . , . . . . . . .. . . .. . . . .. . -. . . . . . . . . -. .-. . . .-... . . . . . . . . . . . . . . . . .. .. . . . . ... .... “._. ... .... . . . ..- .... . ........... ...... SW.“..“. - . .. -.-.. . ...... . ........... . s ......... ..... ...... .... . ... .... . . . . ....... ..... ...-. . . ... C.. . ........ ........ .. . ..w ..... . ..... ......... ...... .. . ... .s.... .. . ..-. ......... .. . . .... w . ._...“. ..... . . . . .-. ..- .... .... . . ..... .. ... .......... ...... . . ...... .... . . .“. ... . .... . ... .-. ... .... . AND M. E. GOLDBERG - .. . . -----**. --.....* ‘I” ... .... ... .... . . . .-, . .. . ..-. .-...- . .. . . .. . .. . .. . . . . * ‘ I I I II 1 I 1 200 ms/div D E H V FP F H H V [ V loo I 1 FP t FP 1 I . . . .-. . . . 1. . . - . . . . . . . ..^.. . ..“.. FIG. 9. Neuron responsive to disappearance of fixation light. A, B: memory-guided saccade task. Data in A aligned to beginning of eye movement, B aligned to disappearance of fixation point-the signal to make a saccade. C-l? fixation task. Data in C aligned to when the fixation light appeared at the beginning of the trial. D, disappearance of fixation light during the trial; E, reappearance of the fixation light; and F, disappearance of the fixation light at the end of the trial. Its activity was related to saccades, but began after the beginning of the eye movement. There were eight antidromically excited neurons ( 15.7%), four in each monkey, that could not be classified as visual, visuomovement, movement, postsaccadic, or foveal. They were a heterogeneous group, and included neurons with I) high spontaneous activity that was suppressed 100 ms before and during saccades to the contralateral hemifield (1 neuron), 2) activity that began after the eye movement in 5. OTHER NEURON TYPES. the visually guided saccade task and anticipated the occurrence of the reward (1 neuron), 3) a burst of activity before an eye movement followed by a high activity rate up to the start of the next trial (1 neuron), 4) a sustained response to visual stimuli in the ipsilateral hemifield (1 neuron), 5) activity that combined an enhanced visual response, anticipatory, and postmovement activity (1 neuron), or anticipatory and postmovement activity (1 neuron), and 6) neurons that discharged briskly during smooth pursuit in certain directions (2 neurons). The activity of FRONTAL EYE FIELD ... . .” . ” .... . CORTICOTECTAL . . ..- m. . . . 1401 . . .” ... . . ...... . .m”. . . . - ........" . NEURONS . ..... ....... ..... ... . . .w ..“. .... ....... . . . . .“. . . . . . . . . . . ..... . . -a.. . . . . . . . . . . “...““. . . . . . . . . .” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .” . . . . . . . . . . . . . . . . . . . . . . .” . ..” . , .” . . . . . . 8 . . . . ” . . . . .W..” m . . . a.. , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .“.. . . . . . . . . . em. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . u.. . . . . . . “m . . . . .” . . . . . . . . . . . . . “. . ” 200 ms, div FP T FP . . .““. “. -...-. ” .“. . . .. ” ... ... . .. . .... ” .... . . “. .” .“. ... .. ” ...... .-.-.e...” ...... m- ..” . .w .... . . . ... .. ..- ““.” . ... .... - . .“_. . w . m . . . . . . . m ... ...... . ... ._.““. ........ . .” S..“.“. .L . . “. ...... . ... .... .. ..” .... . . - “. .... ..-..B” . .rn..” “. “I . . . . . . . . . . . . . . . . ... . . . ... . . . ..... .. ..” ..” ” .. ... . ..... -- . . ..... . ... . ... “.N.W” ..““. . ... .. .- I .. ... .” . . “” . . ” .. ...... ..... ...... ..... . .“. . .” ...... . ... ... ........... . . me .... . . . . . . . . . . ... *.. .“..“. ... “. . . .“.. .... . ... . . . . ........ ..” . ..w.m.- .... . ... . ..““.o. . . .. . . ..... . ..w . . . . . . ...... .... . ... . . . . . .w ..... . .-. ..-. . ....... . .“. ... ... ... . . .... “. .... .“.” . .“-m.o.-. ....... ............ .- . ““. _....“.“. .... . - .......... ... ...... * .. ........... .. . ... . - .. .“. . . 200 ms/div FIG. 10. Response of a complex fovea1 neuron in the fixation (A-B) and saccade (C-D) tasks. A: aligned on disappearance of fixation light during fixation task trial. B: reappearance of fixation light. C-D: activity in a variation of the visually guided saccade task where the peripheral target is always on. C: aligned on disappearance of fixation light. D: aligned on the beginning of the saccade. Note that in C and D, the target light status line begins and ends in the “on” condition, since the target light was never turned off in this task. The monkey was trained to always fixate the central light whenever it was present and make a saccade to and fixate the peripheral target light only when the central light was turned off. two of these neurons is described in more detail below. Figure 11 illustrates the activity of a neuron whose greatest activity occurred after the monkey attained fixation at the very beginning of the trial in the memory-guided saccade task (Fig. 1 IA). This neuron did not respond to either the onset or disappearance of the stimulus light (Fig. 11, B and C). After the initial large burst of firing at the beginning of fixation, the neuron’s activity remained at a high rate throughout the trial and ended with a burst of activity that began after the start of the eye movement (Fig. 11D). This postmovement component of the activity was strongest after saccades to targets located on the horizontal meridian in the contralateral hemifield at - 12’ away from 1402 M. A. SEGRAVES AND *+==== M. E. GOLDBERG B!y=E FP J T I -. . -. . T”“” FP T 1 ..-.w. . . . . . . . . . . . . . . . am.. J . .---w- lp ..“..S. . . . . . . . . . . . . . . . Wm.. 200 ms, 7 FP T T.I”. . .... -M.-w. . ... .... S”. ..... m..-m-. . .... . . ....... . . ..... ......... .-- . ............... .. -. .... . . . ..... . -*- w. . 6 . --.m . . ... . -- . .. . ..w ... . ... 1 . . . ..w.- ... .. ..... .. . .... .” .... . I ..... .. . . . .... . .. / . ... ... . ..I .-..-. . . .... s-.-. --. ... . . .. -..-. - . . . .. .. B-w .... . . .WW” -w- “-w-w-. . s . .- ..w .. .................... .- . . “.I, .... .a.....-- . .... ... ..M ...... ..-...a.-_. . . . . . -...w . .................. ..- .. ., ..-. ... . .... . -. .... -. m.. ... W”. . ..... . -...-. ... ..I “.....- ... - ....... . . . . .... -..- - ... . . . .. . . .. .. ....... . . . . ..- . , . ....... . -. .... “.w”...-.... .... ...... . ... .- .... . ........ .... ... * . .... . . ..- .-. . M”..“. - ..M”.. ........ / .. -” .. .-S.W”. ... ..-. . ...... ........ m... . .. I. .... ....... - , . ... ...... .... . s-s . ........ .- ..a-- . ...... ... .... . a.. ..-e- , “...“. ..“. ..-.. “I.. . . ..- . w.. .... . ...... . .... ... .s- ..... . .. -w..#. ....... .... S.-s. SW. em ..... ... ..-. ........ L 1 . . . ... . ... ... . *- 200 ms/div FIG. 11. Activity of a corticotectal neuron with combined anticipatory and postmovement activity, during a memory-guided saccade task. A: activity aligned on the achievement of fixation, at the beginning of the trial. B: activity aligned on the appearance of the target. C: activity aligned on the disappearance of the target. D: activity aligned on the beginning of the saccade. the center of gaze. It also occurred after saccades made in the dark. Although this neuron responded weakly to the reappearance of the fixation light in the fixation task, the magnitude of the activity occurring before the eye movement in the task illustrated is best described as a form of anticipatory activity. In general, anticipatory neuron activity in the frontal eye field is strongest when the monkey is required to make eye movements to the same target location in consecutive trials. Under these conditions, the events of the trial become predictable, and the monkey anticipates their occurrence (7). For the neuron shown in Fig. I 1, the early activity was not a response to a visual stimulus. The activity preceded the beginning of the eye movement by - 1,200 ms, so it could not FRONTAL EYE FIELD CORTICOTECTAL be considered strictly movement related. Instead, it appears to have anticipated events that would occur near the end of the trial, in particular, the saccade and its associated reward. Another neuron showed a modulation of response during different directions of smooth-pursuit eye movements. It did not respond to either peripheral or fovea1 visual stimuli, and it did not respond in saccade tasks. However, it was active while the monkey tracked~ slowly moving targets with smooth-pursuit eye movements. The neuron preferred tracking movements directed up to the left, a direction contralateral to the neuron’s location in cortex. It was also active, to a lesser extent, during smooth-pursuit eye movements down to the left, but was nearly silent during tracking movements directed ipsilaterally. The neuron was best activated by slow stimulus velocity in the preferred direction. Using a target with sinusoidally varied velocity, and a peak-to-peak excursion of 20”, the preferred frequency was 0.1 Hz, producing a mean eye speed of 4”/s. This neuron had a high rate of activity during the inter-trial interval, and its best activity during smooth pursuit tasks did not exceed its activity during the intertrial interval. Electrical stimulation (0.2-ms pulse width, 330 Hz, 400-ms train, 75PA pulses) at the recording site of this neuron in the frontal eye field produced upward slow eye movements that began -45 ms after stimulus onset, and lasted until the stimulus was turned off. 6. NONRESPONSIVE NEURONS. one neuron (2.0%), antidromically excited from the su- NEURONS 1403 perior colliculus, could not be activated during any of the behavioral tasks. Neurons adjacent to ant idrom ically excitable neurons Most antidromically excitable neurons were isolated during electrode penetrations where only responses to electrical stimulation of the superior colliculus were routinely examined, and neuron activity during visual and eye movement tasks was studied only after an antidromically excitable neuron had been isolated. However, we frequently recorded the activity characteristics of all neurons encountered in a single penetration to ascertain the overall distribution of neuron types that were being sampled by the electrode. As an example, Fig. 12 illustrates the activity of neurons encountered during a penetration through 6 mm of cortex made with a platinum-iridium electrode. Because of the length of this penetration, it is likely that the electrode traveled obliquely through the cortical layers of the frontal eye field, beginning at layer I and ending in white matter after passing through layer VI. The thickness of the frontal eye field cortex from surface to white matter is normally ~2 mm. Two antidromically excitable neurons were isolated during this penetration. Neuronal activity recorded at the beginning of the penetration contained only visual responses, including tonic multineuron visual responses recorded at a depth of 1,502 pm (Fig. 12A). Movement-related activity was first encountered at 3,300 pm, and at this depth the movement component of the multineuron activity was stronger than the visual component. The first FIG. 12. Neurons encountered during penetration through 6 mm of frontal eye field cortex. A-G shows neuronal activity. In each truce H and V are horizontal and vertical eye position, respectively, with 10” calibration mark shown for each pair. For each example of neural activity (A-G) two rasters and histograms are shown. In the left of each pair activity is synchronized on the appearance of the target. In the right of each pair activity is synchronized on the tonic visual activity recorded at 1,502 pm. Memory-guided saccade task. beginning of the saccade. A: multineuron excited neuron with movementNote that activity starts with stimulus and ends at movement. B: antidromically related presaccadic activity, 3,75 1 pm. Memory-guided saccade task. Note absence of response to target onset (left). C and D: neurons with postmovement activity recorded at 3,742 and 3,841 pm. Memory-guided saccade task with zero delay between target light and fixation point disappearance. Note lack of response to target onset (left) and excited neuron isolated, premoveresponse beginning with beginning of saccade (right).E: second antidromically ment activity combined with strong anticipatory activity. Memory-guided saccade task with zero delay. Note activity neurons. Note preceding target onset (left) and burst occurring before movement (right).F and G: postmovement no activity synchronized on target onset. (left) and activity beginning after the beginning of the saccade (right).H indicates the locations of the recording sites for the neurons illustrated in A-G. The vertical rule shows distance traversed by electrode. The asterisks mark the sites at which antidromically excited neurons were found. The activity of these antidromically excited neurons is shown in B and E. See text for additional details. 110° r FP 1 T H v FP T - f I ‘I I 200 ms/div _. FP T- FP T1 _____ . FP T 1loo I ...... ...... ... -. -..... _ ...... ............. .... t_. .. -. . .. .-. -.--. .... . ......... _. _ ... ....... .___ -__._ __ . ..... . -_..... . ........ _ ........... .... .._. -._. _ .... ...... _ ..... ....... .. _. .. ” .. .._. I.. .. .... -_-. -. ....... . ...... __... ..... I, ............ ........... ...... - _ .... ..... .......... . -..... ..... ........ 7 1 200 ms/div FP T- 1 ... .. FRONTAL 7 *. . *... . : . . . . * . , . . . . * *. *. : : . *-. . . . . . . . . ‘1.: *. .- * . . ’ . . ..‘i* a....... ;;: .:I:: :;,* .i .: . . * : ,l;‘fl;!.~~;“i . . . .: * *. . :‘. . . . Iiq!WI$/i !ii~!!!!li:l.:/ $iI;;]]i[ji;j .:I i’I;‘!: 0 0 LJ : -, : ;;!ii;i!i;. a* -.,I’ : . *I. a..;..,. . r-: :-!.. :. :.. . . . : : . .:i . . . ..* . . ; . . . Ii’t ;:i: I ;’ . . . . . . ; . : EYE FIELD CORTICOTECTAL NEURONS 1405 M. 1406 A. SEGRAVES AND antidromically excitable neuron was isolated at 3,75 1 pm (Fig. 12B). This neuron was classified as a movement neuron. It increased its firing rate - 100 ms before the start of the eye movement. However, the bulk of its activity occurred after the beginning of the eye movement. A neuron isolated adjacent to the corticotectal neuron at a depth of 3,742 pm (Fig. 12C) had entirely postmovement activity; it did not begin to fire until after the beginning of the eye movement. A second postmovement neuron was encountered at 3,841 pm (Fig. 120). At 4,050 pm, the second antidromically excitable neuron was encountered (Fig. 12E). This was also a movement neuron, however, its activity was very different from that of the first corticotectal neuron. It exhibited strong anticipatory activity, beginning immediately after the target flash onset in the memoryguided saccade task, and included a premovement burst of activity that peaked before the start of the eye movement. Two additional postmovement neurons were isolated at 4,176 and 4,70 1 pm (Fig. 12, F and G). The penetration was ended at 6,000 pm when the electrode entered white matter. One of the most impressive components of the activity of the corticotectal neuron iso- M. E. GOLDBERG lated at 4,050 pm (Fig. 12E) was the suppression of its activity surrounding eye movements in the off direction. When the monkey was required to make a saccade directed away from the optimal direction for the movement activity of the neuron, there was a strong suppression of the neuron’s activity beginning 100 ms after the onset of the target light in the visually guided saccade task, and continuing through the eye movement (Fig. 13). The optimal presaccadic activity for this neuron was obtained when the target light was presented on the horizontal meridian, 10’ to the right. The suppression of activity surrounding the eye movement was optimal when the target light was presented at 10’ to the left of the center of gaze, near the horizontal meridian. It is interesting to note that the optimal target location for the postmovement neurons illustrated in Fig. 12 was in the lower left (Fig. 12, C, D, and F) and lower right (Fig. 12G) quadrants. The optimal target location for the visual neurons recorded at the beginning of this penetration were in the upper right quadrant. Together these results suggest that frontal eye field visual neurons have an excitatory effect upon movement neurons, and postmovement neurons have an inhibitory effect. However, B A H V loo FP T 1 t FP I T 1 t . . . . . . . . . . . . . . . . . . . . . ..s. . . . 200 ms/div FIG. 13. Suppression surrounding eye movements in the off direction for antidromically excited neuron isolated at 4,050 pm in the penetration illustrated in Fig. 12 (this neuron’s activity is shown in Fig. 12~9. Suppression begins 100 ms after the onset of target light ( 12,176”) in visually guided saccade task (A) and continues until after the end of the eye movement (B). FRONTAL EYE FIELD CORTICOTECTAL NEURONS 1407 n n = 45 Mean = 330 pamps SD = 324 pamps O- ~0 :B $1 2 o= n = 24 SD = 265 n = 26 Mean = 1.97 ms SD = 0.89 ms 0 5 10 n 0 1000 1500 0 1000 1500 0 0 0 d0 m 0 cl 0 - Threshold 5 Latency 10 (ms) FIG. 14. Percent distribution of latencies for antidrofor all corticotectal mic excitation. A: distribution neurons isolated in this study. B: distribution for neurons classified as movement. C: neurons classified as foveal. Bin width is 0.5 ms. these effects do not fully account for the activity of the corticotectal neuron illustrated in Figs. 12E and 13, since the suppressionof its activity begins 100 ms before the start of the eye movement, and thus precedes the activity in the postmovement neurons. One of the striking results of this study was our failure to excite antidromically neurons that had nerinheral visual recebtive fields but pamps FIG. 15. dromic (pamps) Percent distributions of thresholds excitation. Bin width is 50 PA. for anti- not movement activity. We isolated more than 100 of these neurons during the course of our exploration of the frontal eye field, and we were never able to excite one antidromically. We made a number of penetrations specifically looking for visual neurons, both through guide tubes from which we successfully isolated corticotectal neurons, and from simple searching penetrations made after passing through the dura with glass-coated platinum-iridium electrodes. Because visual neurons were common, and antidromic excitation technically feasible in our hands. we feel it is unlikelv that the fron- M. TABLE A. SEGRAVES AND 2. Mean latencies jbr antidromic All neurons Movement neurons Fovea1 neurons Compare movement SD SE n 0.16 0.17 0.42 50 26 11 P latenciesjor ail neurons 2.25 1.97 3.19 1.12 0.89 1.41 with fovea1 B. All neurons Movement neurons Fovea1 neurons Compare movement E. GOLDBERG excitation Mean A. AlI M. NS <o.o 1 co.002 A4ean latencies with latencies G.0 excluded 2.04 1.83 2.62 with fovea1 0.74 0.58 0.68 0.11 0.12 0.26 47 25 NS <0.02 <0.002 Entries include all corticotectal neurons isolated in the frontal eye field, neurons whose activity was classified as movement, and those classified as foveal. Significance levels are for comparison of movement or fovea1 to all neurons, and comparison of movement to foveal. A, includes all latencies for all neurons in each category; B, latencies >5.0 ms have been excluded. tal eye field sends a significant visual signal to the superior colliculus. a standard deviation equal to 324 PA, and ranged from 6 to 1,200 ,uA (Fig. 15). To ensure that high stimulation currents Antidromic Latencies were not exciting extracollicular frontal The latencies for antidromic excitation fibers, we studied the threshold for antidrowere unimodally distributed (Fig. 14). The mic stimulation as a function of location of mean latency for all corticotectal neurons the collicular electrode for 22 of the 5 1 isowas 2.25 ms (range 1.2-6.0 ms). Movement lated antidromically excitable neurons. To neurons had a mean latency of 1.97 ms that do this we moved the stimulating electrode was slightly shorter than that for all corticothrough the superior colliculus and recorded tectal neurons, but this difference was not the threshold current for antidromic excitasignificant. Fovea1 neurons had a mean la- tion at 250-pm intervals in depth. In a few tency of 3.19 ms, which was 0.9 ms longer cases,an electrolytic lesion was made at the than the mean for all corticotectal neurons, minimum threshold site so that its position and 1.2 ms longer than the mean for move- could be determined histologically. Two ment neurons. This difference was signifisuch lesions have been reconstructed, and cant in both instances (Table 2A). Three each was located within the intermediate neurons had latencies >5 ms, and appear gray layers of the superior colliculus (see separate from the main distribution in each Figs. 5 and 7). However, it was difficult to graph. However, when these longer latencies recover electrolytic lesionsmade more than a were excluded from the calculation and com- few weeks before the time at which the monparison of means, the same relationships de- key was perfused, and the number of lesions scribed above were maintained (Table 2B). made in each monkey was limited so that The estimated conduction velocity of single lesion sites could be identified with a frontal eye field corticotectal neurons based high degree of certainty. As an alternative upon their mean antidromic excitation la- means for identifying the anatomical sites tency is 18 m/s (range 7-34 m/s). This as- with lowest threshold, the locations in depth sumesan estimated distance from fundus of where minimum thresholds were obtained the arcuate sulcus (AP+22.0), through interwere correlated with the neuronal activity nal capsule and thalamus, to midcolliculus properties recorded at those depths. For 14 of (AP- 1.5) of 40.5 mm. the 22 antidromic neurons examined, such comparisons could be made directly with Antidromic thresholds collicular neuronal activity recorded during The current thresholds for antidromic ex- the threshold determination experiment. For the other eight antidromic neurons neuronal citation had a mean of 330 PA (n = 45), with FRONTAL EYE FIELD CORTICOTECTAL Multiunit NEURONS Responses: 0 Surface Visual Visual Visual 1 Visual Saccade > Saccade > Visual Saccade > Visual 2 Saccade > Visual Deep layer t”“l”“l”“l”“l”“I”“; 0 100 Threshold 200 for 300 Antidromic 400 Activation 500 600 (ramps) FIG. 16. Threshold for antidromic excitation compared with depth from collicular surface. Based upon multineuron activity indicated on the right side of the figure, the transition between superficial and intermediate layers was at a depth of 1 mm from the collicular surface. The border between intermediate and deep layers was at 2.5 mm. The minimum threshold for antidromic excitation occurred at the transition point between intermediate and deep layers. Antidromic excitation thresholds increased both above and below this depth. activity could not be recorded by the stimulation electrode, but the stimulating electrode depths could be determined by comparison with other penetrations. By these criteria each of the 22 neurons tested had their minimum thresholds within the superior colliculus. The minimum thresholds for these neurons ranged from 7 to 500 PA. For all but one neuron, the minimum threshold site in the colliculus was a reversal point, with increasing thresholds above and below the minimum threshold depth. For one neuron, thresholds were only tested above the minimum threshold site, so we cannot rule out the possibility that its threshold would have decreased at lower depth. Figure 16 shows a comparison of antidromic threshold and collicular neuronal activity for a single neuron stimulated at various sites on a colliculus penetration. Note that the threshold reached a minimum at a depth in the colliculus of 2.5 mm. This depth corresponded to the transition between intermediate and deep layer activity. Just above the reversal point, at 2.250 mm, the threshold for electrically evoked eye movements began to increase with increasing depth, and the movement component of the multiunit ac- tivity was diminished in strength relative to that recorded at 1.750 mm. At 2.500 mm, the phasic movement burst associated with intermediate layer neuron activity was replaced by activity that increased before the monkey achieved fixation and continued until after the end of the eye movement in the memory-guided saccade task. Of the 13 neurons where accurate correlations could be made between threshold reversals and collicular neuronal activity, the reversal points of three neurons were located at depths where superficial layerlike properties were present, including a prominent visual response,little or no movement activity, and a relatively high threshold (generally >50 PA) for electrically evoked eye movements. Nine neurons had reversal points at depths where movement activity was recorded and thresholds for electrically evoked eye movements were low ~50 PA). These include the following. I) Two neurons with reversal points at the transition between superficial and intermediate layerlike activity-identified by the presenceof both visual and movement activity components, with a prominence of visual over movement activity. 2) Five neurons with reversal points located at 200 ms/dlv 200 ms/dlv FIG. 17. Comparison of frontal eye field and superior colliculus premovement activity for low-threshold corticotectal neuron. A: activity in visually guided saccade task for a frontal eye field neuron excited from the superior colliculus with a threshold of 7 PA. B: single-neuron activity recorded at low-threshold site within the superior colliculus. Rasters are aligned upon target onset. In both A and B the amplitude of the target’s displacement from the fixation point was 10”. ii 8~~ B FRONTAL EYE FIELD CORTICOTECTAL 1411 NEURONS -2 4 f4 .\ / \ / 4 ) zq 001 1412 M. A. SEGRAVES AND sites where activity characteristic of the intermediate layers was recorded. These characteristics include strong movement activity, weak or no visual response, and the lowest threshold for electrically evoked eye movements. 3) Two neurons with reversal points at the transition between intermediate and deep collicular layers. At this depth, there was a decrease in the strength of the movement activity, a return of visual activity, and an increased threshold for electrically evoked eye movements. One neuron’s reversal point was localized to a depth with deep layerlike activity where, in addition to increased visual and decreased movement activity, the electrical stimulus train used to evoke eye movements appeared to be mildly aversive to the monkey at currents of 75 PA, suggesting that the electrode was in the vicinity of the central gray matter. In general, the lowest thresholds occurred when the movement fields of the collicular multiunit activity and the frontal eye field neuron were alike. An example of this relationship is provided in Figs. 17 and 18. The corticotectal neuron illustrated in Fig. 17A had movement activity that was strongest preceding saccades to target positions on the vertical meridian, 10’ below the horizontal meridian. This neuron was antidromically excited from the superior colliculus with a minimum threshold of 7 PA. Premovement single neuron activity recorded at the collicular stimulation site (Fig. 17B) had a preferred target location that was similar to the best target location for the frontal eye field neuron. In contrast, the optimal target locations for the corticotectal neuron illustrated in Fig. 18A and multineuron activity recorded at its collicular stimulation site (Fig. 18B) differed in both amplitude and direction from the center of gaze. The center of the movement field of the frontal eye field neuron was at 15” radius and 45” angle, and at 10’ radius and 270” angle for the collicular activity. The minimum threshold for antidromic excitation of this visuomovement neuron was 160 PA. The ideal situation exemplified by the electrode pair illustrated in Fig. 17 was rarely realized, however, because of the different topographical organizations of the superior colliculus and frontal eye field. M. E. GOLDBERG We have con rpared antidromic excitation thresholds with a value expressing the vector difference between frontal eye field and collicular saccade vectors for data obtained for 25 frontal eye field visuomovement and movement neurons (Fig. 19). The “index of vector difference” was equal to the amplitude of the vector difference between optimal frontal eye field and collicular saccade vectors divided by the sum of the amplitudes of the two saccade vectors. This method was chosen to enable us to compare data from both large and small eye movement sites. Our hypothesis was that stimulation and recording sites with similar optimal saccade vectors would have low thresholds. Since equal saccade vectors result in an index of vector difference of 0, and opposite saccade vectors result in an index value of 1, it was expected that low thresholds would be associated with index values near 0, and high thresholds with index values approaching 1. In fact, there was a significant linear correlation (Y = 0.62) between the regression of index of vector difference upon log of threshold for antidromic excitation (P < 0.001). These data suggest that small increases in the vector difference between the stimulation 0 n = 25 r = 0.62 p < 0.001 1 o-o,,, I I rI11.., 10 Threshold l I 100 l 8 l 1 a l I I .““7 1000 (ramps) FIG. 19. Effect of topography of recording and stimulation sites upon threshold for antidromic excitation. Index of vector difference is equal to the amplitude of the vector difference between optimal saccade vectors at frontal eye field and collicular sites divided by the sum of the amplitudes of the two vectors. The index of vector difference would equal 0 for identical saccade vectors and 1 for saccade vectors that are in opposite directions. The data were taken from 25 antidromically excited visuomovement and movement neurons. Threshold is ‘. nlotted on a log scale. FRONTAL EYE FIELD CORTICOTECTAL NEURONS 1413 and recording sites result in large increases in threshold. For example, a 23% increase in difference between saccade vector angles, that is for saccades of equal loo amplitude but increase in angular difference from 44 to 54”, would be accompanied by a doubling of threshold for antidromic excitation from 50 to 100 ,uA. frontal eye field and superior colliculus, as well as several technical aspects concerning these experiments. Nonhomogeneous projection of frontal eye jield activity to the colliculus Figure 20 compares the distributions of our population of identified corticotectal neurons (solid bars) with the population of all frontal eye field neurons described by DISCUSSION Bruce and Goldberg (hatched bars) (7). In this study, we have demonstrated that Fifty-three percent of the corticotectal the projection from the frontal eye field to neurons were classified as having movement the superior colliculus, first described using activity, compared with 11% in the general anatomical techniques, can also be shown sample. The second largest single group of using electrophysiological techniques in corticotectal neurons were those with fovea1 awake monkeys. The most striking result is responses. They included 20% of the corticothat there seems to be a selective enrichment tectal neurons, but only 7% of all frontal eye for two neuron types, those in which movefield neurons. There were no neurons antiment activity predominates, and those with dromically excited from the superior collicfovea1 visual activity. There is also a selection ulus that could be classified as preferring against two types of neurons, those with pe- purely peripheral visual stimuli. Neurons ripheral visual receptive fields and those whose predominant activity occurs during whose discharge only occurs during and after and after the saccade only rarely project to saccades. We will discuss the implications of the superior colliculus. these results for our understanding of the Given such a striking difference between generation of saccadic eye movements by the all the neurons in the area and the collicular 0 GO q q All frontal Neurons eye activated field neurons antidromically (Bruce & Goldberg, from superior 1985), colliculus, n = 752 n = 51 Movement Visual movement FIG. 20. Comparison of distribution among activity categories of frontal eye field neurons from the superior colliculus (solid bars) to the distribution of all frontal eye field neurons Goldberg (7) (hatched bars). excited reported antidromically by Bruce and M. A. SEGRAVES AND projection neurons, we must consider whether or not this difference could be an experimental artifact. The first possibility is always sampling error. However, in order to gather our modest population of antidromic neurons we had to record from a much larger population of frontal eye field neurons. We made a special effort to find neurons of the types that we could not drive antidromically. Therefore probabilistic sampling error is unlikely. The second possibility is that there is a physical difficulty that makes it possible for antidromic spikes to invade the somata of some corticotectal neurons, but not others. This is unlikely because anatomical studies showing the somata of frontotectal projection neurons fail to distinguish multiple morphologies for such neurons. They are all large layer V pyramidal neurons (15, 34). Therefore it is likely that the population of antidromically excited neurons was not terribly biased by a systematic error. The next problem is whether or not an electrode in the superior colliculus excites frontal eye field fibers other than frontotectal ones. This might seem especially likely in view of the large currents needed to excite some neurons. Threshold currents for antidromic excitation ranged from 6 to 1,200 PA, with a mean of 330 PA and standard deviation of 324 PA. The administration of these currents within the superior colliculus undoubtedly resulted in both passive and transsynaptic spread of electrical activity for some distance away from the tip of the stimulating electrode (2, 38, 42). An estimate based upon Ranck’s review of several studies of mammalian CNS stimulation suggests that the spread of passive current from a 330-PA source could excite axons l,OOO1,500 pm from the electrode tip. A ~-PA source (one standard deviation below the mean threshold in this study) could excite axons from 70 to 140 pm away, and a 654-PA stimulus has a potential range of 1,3001,800 pm. Our stimulation sites were presumably in the vicinity of unmyelinated axonal endings and terminals of frontal eye field neurons. The experiments reviewed by Ranck involved stimulation of myelinated axons only. Unfortunately there have been no reports of the relative sensitivities of axon terminals versus axons en passage to applied extracellular current. Thus our estimates of M. E. GOLDBERG current spread are only rough approximations. Frontal eye field axons projecting to the midbrain and pons follow both transthalamic and pedunculopontine pathways (26, 32) (Stanton, personal communication). Transthalamic fibers travel within and adjacent to the internal medullary lamina. At the level of the posterior thalamus, the transthalamic pathway bifurcates, with corticotectal axons passing dorsally through the pretecturn to terminate in the superior colliculus, and the remaining axons passing ventrolaterally toward the mesencephalic reticular formation and pontine tegmentum. Frontal eye field axons within the pedunculopontine pathway travel within the cerebral peduncle and project to the pontine and reticularis tegmentis pontis nuclei. Recent evidence suggests that this pathway does not include corticotectal axons (Stanton, personal communication). Although the potential range of our stimulating currents were often large, there was no indication that neurons antidromically excited in the frontal eye field were being excited by current spread outside of the superior colliculus. In every case tested (4 1% of the antidromically excited neurons), the reversal point in depth where the minimum threshold for antidromic excitation was obtained was located within the superior colliculus. Thus it is unlikely that we were stimulating frontal axons projecting to the mesencephalic reticular formation or the region of the oculomotor nuclei instead of frontotectal axons. It is most likely that high thresholds for antidromic excitation were the result of a lack of overlap between the movement fields at the site of the collicular electrode and the movement field of the antidromically excited neuron. The frontal eye field-collicular pathway connects equivalent points within each topographic representation (29, 55), and our efforts to stimulate and record from sites with similar movement fields were meant to take advantage of this relationship. However, it was often difficult to position our electrodes within overlapping movement fields because of the different topological representations of the intermediate layers of the superior colliculus and the frontal eye field. The colliculus contains a simple visuotopic map FRONTAL EYE FIELD CORTICOTECTAL of desired movement (45), but the frontal eye field combines a dorsoventral representation of saccade amplitude superimposed upon repetitive representations of saccade direction, such that a single saccade vector is represented at multiple nonadjacent locations (8, 46). This produced frequent changes in saccade direction during a single frontal eye field penetration and resultant mismatches with the fixed collicular saccade vector. In the cases where the saccade vectors overlapped, the threshold was usually quite low; when they did not overlap, the threshold was higher. Functional aspects offrontal neuron types eye field NEURONS. We have demonstrated that the principal component of the frontal eye field’s input to the superior colliculus consists of increased neuronal activity preceding saccadic eye movements, both visually and memory guided. This input originates from neurons with presaccadic activity in cortical layer V that terminate in the superior colliculus in a topographic manner. Our results complement the findings of recent stimulation and neuron recording studies (7, 8) showing that minimum threshold stimulation sites (as low as 10 PA) within the frontal eye field are likely to be located near neurons with movement activity. Low-threshold sites were generally located within cortical layers V and VI, and 63% of the movement and visuomovement neurons were located within this region. In addition, Bruce and colleagues found a close correspondence between the optimal direction within the movement fields of adjacent neurons and the saccade vector generated by electrical stimulation. These present results suggest, therefore, that one pathway by which electrical stimulation or natural neuronal activity in the frontal eye field can initiate saccades is through this direct projection to the intermediate layers of the superior colliculus. This contribution will be better understood when we are able to determine the information content of the signal carried by the axons of corticotectal movement neurons. It is possible that the frontal eye field’s movement output is specifically related to motor parameters for the impending saccade, since lesions of the frontal eye field and superior colliculus both have an MOVEMENT NEURONS effect upon saccade dynamics, cadic velocity ( 10, 25). 1415 including sac- NEURONS. An unexpected finding in these experiments is the strength within the frontotectal projection of foveally responsive neurons. Fovea1 neurons comprised a small fraction of the total population of frontal eye field neurons examined by Bruce and Goldberg (7), but formed the second largest population of frontal eye field corticotectal neurons. Twenty-two percent of antidromically excited neurons were classified as fovea1 neurons versus 7% in the total population of frontal eye field neurons. These neurons were typically suppressed or excited by fovea1 light stimuli and discharged most strongly in our task at the signal to make a saccade or during attentive fixation, respectively. There were equal numbers of fovealon and foveal-off neurons. The observation that frontal eye field neurons discharge during fixation was first made by Bizzi (4). The neurons were studied most extensively by Suzuki and his co-workers (56, 57), who showed that the fovea1 responsiveness of these neurons explained much but not all of their activity. Fovea1 neurons may play a role in the act of attentive fixation, which is known to be physiologically different from merely maintaining the eye in a given orbital position (14, 19, 40). They send a message complementary to that of the movement neurons: a signal either to suppress or initiate a saccade. It is possible that the artificiality of our task, in which a visual stimulus bears the signal to suppress or initiate a saccade, may be responsible for the fovea1 responsiveness of these neurons, which are otherwise more closely associated with a fixation or end-of-fixation role in the untrained monkey. Presumably neurons active during attentive fixation would provide a suppressive effect upon superior colliculus movement neurons and thereby assist in the maintenance of fixation. This effect may be direct or indirect. Layer V pyramidal neurons in the frontal eye field do not appear to contain the inhibitory transmitter y-aminobutyric acid (52), although they may use another inhibitory neurotransmitter. It is more likely that they act indirectly via collicular interneurons. This potential inhibitory effect of frontal eye field FOVEAL M. 1416 A. SEGRAVES AND neurons is similar to that demonstrated for substantia nigra neurons that project to the colliculus (24). The frontotectal suppressive effect would be stronger specifically during attentive fixation, unlike the nigra signal, which is always maximal, except around a saccade. OTHER CORTICOTECTAL NEURON TYPES. Two neurons in our sample of corticotectal neurons seemed to have activity related to the performance of smooth-pursuit eye movements. This finding is of interest in light of recent reports of deficits in smoothpursuit eye movements in monkeys with frontal eye field lesions (28, 36). Neurons active during smooth pursuit have been described previously in the frontal eye field (5), where they were found at the same sites associated with the evocation of smooth pursuit by electrical stimulation (8). These neurons have not been exhaustively characterized to determine if they could be movement neurons for pursuit or if they are instead discharging in response to target movement or the retinal slip induced by the stationary environment on the moving retina. The superior colliculus has not been shown to have a role in smooth pursuit, and it is possible that these neurons are, in fact, suppressing small saccades, similar to the role postulated for the fovea1 neurons. A few other neurons discharged in relation to anticipation of the reward or the next trial, were suppressed around saccades, or combined anticipatory, postmovement activity, and/or visual activity. These neurons were unusual in these experiments and unusual in previous ones, and it is difficult at this point to understand their function or significance. NEURONS FIELDS. WITH PERJPHER +t VISUAL None of the corGcotecta1 neurons in our sample could be classified as peripheral visual neurons. Thus one can assume that the visual activity present in the superior colliculus does not originate from the frontal eye field. Only 10% of the visual neurons characterized in the work of Bruce and colleagues (8) were located within a region where thresholds for evoked eye movements were ~50 PA. Although they do not project to the superior colliculus, visual neurons are still likelv to be involved in the generation of M. E. GQLDBERG saccades. Fifty percent of frontal eye field visual neurons are enhanced before saccades to the stimulus in their receptive field (62), and, unlike other types of attentive movements, this enhancement is spatially selective and specific to saccades (18). Our results suggest that these neurons participate in the intrinsic generation of a movement signal within the frontal eye field, rather than project directly to the oculomotor system. Of the visuomovement neurons, some with strong movement activity project to the tectum, but those with visual predominance do not. This result reaffirms the likelihood that visuomovement neurons do not comprise a unique class of neurons by themselves, but rather belong to a continuum extending from visual to movement-related activity. Comparison to other corticotectal neurons Corticotectal neurons within striate cortex have been examined in both cats (41) and monkeys (13). In both species these neurons belong to a subset of complex visual receptive-field types. In cats, removal of visual cortical input to the colliculus results in a loss of direction selectivity as well as input from the ipsilateral eye in superficial layer neurons and also affects receptive-field properties of deep layer neurons (47, 58). However, in the monkey, ablation or cooling of visual cortex only affects the visual responses of neurons within the intermediate and deep layers of the superior colliculus (50). The average conduction latencies for corticotectal neurons in monkey striate cortex were longer (4.6 ms) (13) than those in our sample of frontal eye field neurons (2.25 ms). The conduction velocity reported for striate corticotectal neurons was an average of 8 m/s (range 3- 19 m/s) versus an estimated 18 m/s for frontal eye field corticotectal neurons. Although prestriate and parietal neurons have been shown by anatomical methods to project to the intermediate layers of the superior colliculus (3 1, 37) antidromic studies have not been done to characterize them physiologically. Other prefrontal neurons, especially those more anterior to the frontal eye field, have also been shown by anatomical methods to project to the colliculus (20, 34), but the nature- of this projection is also STRIATE CORTICOTECTAL. FRONTAL EYE FIELD CORTICOTECTAL not known. We did not attempt antidromic excitation in frontal areas that we had not characterized as being in the low-threshold arcuate frontal eve 4 field. The role of the frontal eyefield in the generation of eye movements These results contribute to the growing evidence that the arcuate frontal eye field is important in the initiation of purposive saccadic eye movements. We have now established that the oculomotor region of the superior colliculus, the intermediate layers, receives a distinct oculomotor message from the frontal eye field. The message is twofold: it tells about the state of fixation and fovea1 stimulation and sends a command to make a movement of certain dimensions. The superior colliculus and the frontal eye field can function independently in the generation of saccades. Lesions of the superior colliculus do not affect the generation of saccades by electrical stimulation of the frontal eye field (48), and monkeys can make visually guided saccades in the absence of the frontal eye field or the superior colliculus, although they cannot make visually guided saccades at all when both are ablated (5 1). Recent results suggest that some types of saccades do, in fact, require the frontal eye field. We have shown that monkeys with unilateral frontal eye field lesions have difficulty learning to make saccades to remembered targets, and when they do learn, the motor performance of memory-guided but not visually guided saccades is impaired ( 10). Bruce has shown that although normal monkeys can make predictive saccades, monkeys with frontal lesions cannot (6). Guitton and colleagues have shown that humans with frontal lesions have difficulty making saccades away from a visual target, and instead make inappropriate saccades toward the target (2 1). Thus there is a repertory of saccades, characterized by behavioral complexity, that require the presence of the frontal eye field. Our results suggest that in normal monkeys the signal for these as well as visually guided saccades progress from the frontal eye field to the intermediate layers of the superior colliculus, which in normal monkeys then serve as a final common path for saccades (49). Neurons in the superior colliculus NEURONS 1417 discharge before all saccades (49, 6 1) and the region has a monosynaptic projection to the long-lead bursters in the brain stem reticular formation (43). The arcuate frontal eye field can affect this presaccadic final common path in three ways. The first is through the direct targeting signal to the colliculus that we have demonstrated here. The second is through the fovea1 signals, which could directly trigger or suppress a collicular saccadic signal. The third is by affecting the substantia nigra. The frontal eye field projects to the head of the caudate, which contains a presaccadic signal similar in quality but reversed in sign from that of the substantia nigra. This frontal-caudate signal could inhibit the subtantia nigra and result in a presaccadic release of the nigral suppression of the superior colliculus. Thus the frontal command to the colliculus would be exceedingly powerful because it combines an excitatory signal with the release of a suppressive one. When a monkey is actively fixating, thresholds for evoking saccades from the superior colliculus (22) are elevated. Presumably this is true because saccades that occur without changes in frontal and nigral activitv must overcome the suppression which inhibits them. Since monkeys and humans can make normal saccades after lesions of the frontal eye field, the colliculus must be able to function on its own, and under certain circumstances, for example spontaneous saccades made in total darkness, there is little or no frontal signal (4, 7). We submit, however, that when the normal monkey makes purposive saccades, these saccades are organizaed by the frontotectal pathways discussed here. ACKNOWLEDGMENTS The authors are grateful to the technical staff of the Laboratory of Sensorimotor Research for their invaluable help: A. 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