European Journal of Neuroscience. Vol. 7, pp. 1005-1011, 1995 0 European Neuroscience Association

Topographic Distribution of Fixation-related Units in the Dorsomedial Frontal Cortex of the Rhesus Monkey

Kyoungmin Lee and Edward J. Tehovnik Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Keywords: oculomotor control, eye position, visual fixation, single-unit recording

Abstract

Most cells in the dorsomedial frontal cortex of the rhesus monkey had activity related to saccadic eye movement andlor visual fixation. This activity changed depending upon the position of a fixation target, which suggested coding for the target location in spatial coordinates. Further analysis of such activity revealed a topographical distribution of neurons: neurons in the rostral part of the area were more active with eyes to the contralateral position, while those in the caudal part were more active with eyes to the ipsilateral position; also, cells in the medial part of the area had higher activity with a downward fixation position, whereas those in the lateral part had higher activity with an upward fixation position. This distribution of units was in agreement with the map of termination zones of saccadic eye movements evoked by electrical stimulation of the same area. These observations provide evidence for the hypothesis that the dorsomedial frontal cortex is organized in spatial coordinates and is involved in specifying the position of visual fixation.

Introduction That the dorsomedial frontal cortex (DMFC) of the primate contains an eye field has been established by the finding that electrical stimulation of this area evokes saccadic eye movements (Schlag and Schlag-Rey, 1987; Mann et al., 1988; Schall, 1991b; Bon and Lucchetti, 1992; Tehovnik and Lee, 1993). The existence of an eye field in the DMFC is further supported by the observation that activity of single cells in this region is modulated by saccadic eye movements and fixation (Schlag and Schlag-Rey, 1987; Mann et al., 1988; Schall, 1991a; Bon and Lucchetti, 1992; Schlag et al., 1992). Presaccadic activity occurs with self-initiated as well as with visually triggered saccades (Schlag and Schlag-Rey, 1985, 1987). Also, fixation-related units have been identified that are modulated by changes in eye position (Bon and Lucchetti, 1992; Schlag et al., 1992).

Saccades elicited by stimulation of the DMFC terminate within a certain region of craniotopic space, the termination zone, irrespective of initial eye position (Schlag and Schlag-Rey, 1987; Mann et al., 1988; Schall, 1991b; Bon and Lucchetti, 1992; Tehovnik and Lee, 1993; Tehovnik er al., 1994; but see Russo and Bruce, 1993, for an opposite view). This is in contrast with stimulation of the frontal eye fields or superior colliculi where evoked saccadic eye movements have constant direction and amplitude regardless of initial eye position and, therefore, the evoked saccades do not terminate in a common space (Robinson and Fuchs, 1969; Robinson, 1972; Schiller and Stryker, 1972; Bruce et al., 1985; Tehovnik and Lee, 1993). This difference in the properties of saccades evoked by electrical stimula- tion led to the hypothesis that the DMFC is organized in craniotopic coordinates (Tehovnik and Lee, 1993), unlike the frontal eye fields or superior colliculi, which are thought to be organized in retinotopic coordinates (Robinson and Fuchs, 1969; Robinson, 1972; Schiller and Stryker, 1972; Bruce et al., 1985).

Furthermore, stimulation of the DMFC reveals a map of termination zones of the evoked saccades (Tehovnik and Lee, 1993). Saccades elicited by stimulation of the rostral DMFC terminate at extreme positions contralateral to the stimulated hemisphere, while those elicited by stimulation of the more caudal DMFC terminate at central, slightly ipsilateral positions. Similarly, stimulation of the medial DMFC elicits saccades that terminate at downward eye positions, whereas stimulation of the lateral DMFC elicits saccades that terminate at upward eye positions. This map of termination zones was invariant to changes in the position of the head with respect to the body. Therefore, the DMFCs in the two hemispheres together represent the whole range of eye positions in head-centred coordinates.

In this study, we examined responses of units in the DMFC, focusing on the modulation of these responses in relation to eye position. This is to determine if there is a correspondence between properties of unit activity and the topographic arrangement of termina- tion zones as described by electrical stimulation. Part of this work has been reported in an abstract (Lee and

Tehovnik, 1991).

Materials and methods Subjects Three adult male monkeys (Macaca rnulatta), A, L and Y, were used. The monkeys were deprived of water overnight before experimental testing, after which they were allowed to drink to satiation. The animals were provided for in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and the guidelines of the Massachusetts Institute of Technology Committee on Animal Care.

Correspondence ro: Kyoungmin Lce, Department of Neurology, The New York Hospital-Cornell Medical Center, 525 East 68th Street, New York, NY 1002 I , USA

Received 27 June 1994. revised 23 November 1994. accepted 2 December 1994

1006 Topography of fixation-related units in the DMFC

m w Y Monkeys were prepared for unit recording as well as for electrical stimulation of the DMFC with sterile surgical technique and anaes- thesia with pentobarbital (30 mgkg). Prior to the initiation of the experiments, a scleral search coil was implanted under the conjunctiva to monitor eye position and a stainless-steel post was attached to the skull to restrain the head painlessly. The scleral search coil was placed on the right eye in monkeys A and L, and on the left eye in monkey Y. After the monkeys were trained with behavioural tasks, a metal cylinder was implanted over the DMFC in contact with intact dura after a craniotomy.

Unit recording and electrical stimulation A PDP 31/73 computer was used to record action potentials ( I kHz sampling rate), eye movements (200 Hz sampling rate), and other task-related events.

Glass-coated platinum-iridium electrodes with an impedance of 0.5-2.0 MR at 1 kHz were constructed for both unit recording and electrical stimulation. Electrodes were introduced perpendicular to the dural surface with a hydraulic microdrive. The action potentials were amplified (Bak A-IB), filtered (Krohn-Hite 3750) and discrim- inated (W Instruments 121).

Electrical stimulation was delivered by constant-current biphasic pulses using a Grass S88 stimulator attached to a pair of constant- current stimulus isolation units (Grass PSIU6B). For each biphasic pulse, a cathodal pulse was delivered first followed immediately by an anodal pulse. Both pulses had the same amplitude and duration. Current was monitored by a voltage drop across a 1000 R resistor that was in series with the return lead of the stimulator, displayed on a Tektronix Oscilloscope (model 5103N) and read as the amplitude of one pulse of a biphasic pair.

Behavioural task The visual stimuli were red light-emitting diodes (LEDs) embedded into a board that was located 51 cm in front of a head-restrained monkey. The LEDs were spaced at 10 degrees with a total of 49 (7x7) LED slots subtending 60x60 degree2 of the visual space. A set of five LEDs was selected for one experimental session, typically one at the centre and others in all quadrants of craniotopic space. On a trial, two of the five LEDs were turned on and off in succession. The selection of the LED pair for illumination was randomized from trial to trial, so that the animal could not predict the location of the next target in advance of its appearance. All the experiments were conducted in complete darkness.

An animal was required to make a saccade from the first to the second LED as soon as the second LED was illuminated, and it had to remain fixated on an LED for a variable duration (ranging from 800 to 1200 ms). Apple juice was dispensed as a reward if the animal made a correct response.

Classification of unit activity Criteria for defining fixation-related and saccade-related units were as follows. Time periods were divided by events in the visually guided saccade task, as depicted in Figure 1, and then a mean impulse frequency of unit activity was computed for each period. The baseline activity for a unit was regarded as the mean impulse rate during a pretrial period (PTP) of 1000 ms prior to the appearance of the first target. Two saccadic periods (SACI and SAC2) and two fixation periods (FIXI and FIX2) were defined in relation to two visual targets (TI and T2). SAC1 and SAC2 began at the appearance of the first

Target 1 I 1

Target 2 r

Eye position

/ /

PTP SAC 1 FIX1 SAC2 FIX2 ’ 1000 r n s e c w “800 msec “ 800 mse

Reward

FIG. I . The drawing depicts events in the visually guided saccade task. Analysis of unit activity was conducted over five time periods defined by the events. A pretrial period (PTP) started loo0 ms prior to appearance of a target (TI). The saccadic period (SACI) began with the presentation of the target (TI) and ended 200 ms after the completion of a saccade to that target. The saccade period (SAC2) began with the presentation of the other target (T2) and ended 200 ms after the completion of a saccade to that target. The fixation period (FIXI) started 200 ms after the completion of the saccadic eye movement to the first target (TI) and ended when the cue to generate a saccade to the second target (T2) was presented. The fixation period (FIX2) started 200 ms after the completion of the saccadic eye movement to target (T2) and ended when a reward was delivered. The duration of FIX1 and FIX2 varied randomly between 600 and 1200 ms.

target (Tl) and second target (T2), respectively. These periods were defined to end at 200 ms after completion of each saccadic eye movement in order to .include the immediate postsaccadic activity. FIXl and FIX2 commenced at the end of each saccadic period (SACI and SAC2 respectively) and lasted until a cue to make a saccade was given by turning off the first target (in the case of FIXI) or until a reward was delivered (in the case of FIX2).

A mean and standard deviation of impulse frequencies during each period were computed for a group of trials having the same TI and T2 positions. There were a total of 20 groups [five possible fixation positions (TI) each with four possible targets (T2)], and the number of trials for each group ranged from five to 15. For units exhibiting significant change in unit activity during a task, a r-test was used to determined whether the unit displayed fixation-related or saccade- related properties.

A unit that had activity during FIXl that was significantly different (P < 0.01, two-tailed) from the activity of the pretrial period was classed as a fixation-related unit. Fixation-related units were then included in further analysis with respect to eye position as described below to determine whether or not their activity during saccadic periods was also modulated by the task. A unit that had activity during SAC2 that was significantly different from the activity of the pretrial period was classed as a saccade-related unit.

If there was no significant change in unit activity (P > 0.01) from the baseline in any of 20 groups of trials, then the unit was considered to be unmodulated and was therefore excluded from further analysis.

Quantification of fixation-position dependency We and others (Schlag et al., 1992) observed that the eye position dependency of fixation activity changes monotonically across cranio- topic space for most DMFC neurons. That is, no cells that we recorded from had increased fixation activity for only central fixations. Therefore, we computed the position bias of unit activity by comparing fixation-related activity during FIXl among four peripheral LED positions, excluding the centre position. The fixation positions were

Topography of fixation-related units in the DMFC 1007

A

Posterior

B Monkey Y Anterior

MLS ML2 I ML2 ML4

- 5 mm

FIG. 2. The areas investigated in the DMFC of monkeys A and Y are shown in panels A and B. The location of recording sites is indicated with respect to the interaural line (A26 to A32 for monkey A and A25 to A28 for monkey Y) and the midline (MLI to ML5 for monkey A and ML2 to ML5 for monkey Y). measured in millimetres. With monkey A, the recording well was positioned obliquely and slightly to the left so as to allow the exploration of the mesial surface of the hemisphere, whereas with monkey Y the recording well was centred on the midline and positioned more posteriorly. This posterior placement prevented us from examining the rostra1 third of the DMFC in monkey Y. A recording site is marked by a circle whose size indicates the number of units recorded from the site, as shown in the legend. Black circles indicate that >50% of the recorded cells were fixation-related, while the open circles indicate that <50% of the recorded cells were fixation-related. The principal sulcus (Ps), arcuate sulcus (As) and central sulcus (Cs) are indicated. A scale bar is shown at the top left comer. Monkey L is being used for other experiments.

one in each quadrant of the craniotopic space, at 30 degrees to the left or to the right from the centre in the horizontal dimension and at 20 degrees above or below the centre in the vertical dimension.

The position bias of a unit was defined as the vector-average of four activity vectors [F(i)] for the four fixation positions. An individual activity vector, F(i), for each fixation position had a direction, angle(i), indicating the direction of the fixation position from the centre of visual space, and an amplitude, fFlxI(i), indicating the mean unit discharge frequency of the unit during FIXI. This was formulated as follows:

Position bias = (Px, Py) = ( l/maxf,fFIxl(i))) (average(F,(i)), average(F,( i))) where F(i) = (Fx(i), F,(i)) = (fFIXI(i)Xcos(angle(i)), fmxl( i )X sin( angle(i))).

A

- 80 Hz

-1 400 0 1800 msec

B

. . -1 400 0 1800 msec

FIG. 3. A neuron exhibiting fixation-related activity recorded from the left DMFC of monkey L is illustrated. From top to bottom, each panel (A and B) contains an illustration of the target positions in the task, the eye traces of the horizontal component of the eye movements (where up represents a rightward movement and down represents a leftward movement), the corresponding rasters of action potentials, and the cumulative histogram of action potentials. The left and right sets of larger tick marks on the rasters indicate when TI and T2 respectively appeared on each trial. The record of eye movements and units is aligned with respect to the beginning of the fixation at T1. Trials with TI at 30 degrees to the right and 20 degrees below the centre of craniotopic space are shown in A. Trials with TI at 30 degrees to the left and 20 degrees below the centre of craniotopic space are shown in B. T2 was always at the centre of craniotopic space.

The position bias was normalized to the maximum discharge frequency exhibited by a unit, so that the amplitude of position bias could range from 0 to I , whereby 0 indicated no bias and 1 indicated a maximal bias.

Results Fixation-position dependency of neuronal activity in the DMFC Out of 274 cells that were recorded from the DMFC of the three animals (115, 93 and 66 from monkeys A, L and Y respectively), 17 1 were fixation-related (62.4%, 171/274). The proportion of fixation- related units was not different among the three animals (64.3, 59.1 and 63.6% for monkeys A, L and Y respectively, P > 0.5, x2 test). Of the fixation-related cells, 44% (7511 71) began to fire tonically before the saccade arrived on target. There were 42 neurons (15.3%, 42/274) that were related only to saccadic eye movements. The remaining 61 units were found to be unmodulated (22.3%, 611274). The recording sites of monkeys A and Y are shown in Figure 2.

In Figure 3 is an example of a fixation-related cell that had an

1008 Topography of fixation-related units in the DMFC

Position-bias vectors ES-evoked saccades

1

-30 0 30 (Deg.1 1

Horizontal eye position in degrees

FIG. 4. Mean impulse frequencies during FIX1 recorded from the unit shown in Figure 3 are plotted as a function of fixation position. For details see Figure 3 and the text.

increase in activity during fixation as well as during saccadic eye movements. High unit activity was maintained during FIX1 when the monkey fixated a target (TI ) located in the hemispace contralateral to the hemisphere containing the unit (Fig. 3A), whereas low unit activity was maintained during FlXl when the target (TI) was located in the hemispace ipsilateral to the hemisphere (Fig. 3B). When the monkey was not fixating a target, as during the pretrial period, the unit exhibited an intermediate level of activity. During the pretrial period there was no systematic relationship between the position of the eye in the orbit and the modulation of the unit. This was characteristic of all fixation-related units studied in this investigation.

Unit firing frequency during FIX1 for the same unit is plotted as a function of fixation position in Figure 4. When compared with the baseline activity during the pretrial period (22.4 Hz), the activity of this unit during FIX1 was increased for fixation positions at 30 degrees to the right side of craniotopic space, and the activity was depressed for all other fixation positions. The difference was statistically significant for all fixation positions ( P < 0.01, two-tailed t-test; see Materials and methods). Note that in this case the amount of change in FIX1 activity was not completely planar across the fixation positions.

Topographic distribution of fixation-position dependency Figure 5 illustrates the topographic distribution of position biases along the rostrocaudal axis (A3 1 to A27) of the left DMFC of monkey A (Fig. 2A) (see Materials and methods for calculation of position bias). The position bias vectors of units studied at five sites in the DMFC are shown in Figure 5 , left column, where each of the five panels represents vector space. The amplitude and direction of the position bias for a unit is represented by the distance and direction of a cross from the centre of vector space.

At the rostral site (A31), most units had position biases directed towards the visual hemispace contralateral to the hemisphere from which the units were recorded, whereas at the caudal site (A27), most units had biases directed towards the visual hemispace ipsilateral to the hemisphere investigated. There was a gradual change in the horizontal component of the position bias of units going from rostral to caudal sites in the DMFC.

This change in position bias corresponded to the change in the location of termination zones as determined by electrical stimulation of the same sites (A31 to A27) in the DMFC. Examples of saccades

1

A29

A 2 8 f i -30 O 30 (Deg.) 4

FIG. 5. In the left column, five plots of position bias vectors in polar coordinates are presented for each of the five sites (A31 to A27) studied along the rostrocaudal axis of the left DMFC of monkey A (Fig. 2A). The sites were located between 2 and 3 mm from the midline. In each plot, a cross symbolizes the end-point of a position bias vector that originates from the centre of the plot. The direction of a vector indicates the direction of position bias of a unit, and the length of the vector indicates the degree of position bias normalized to the maximal firing frequency of that unit. For details of the calculation of the position vector see Materials and methods. In the left column, stimulation-evoked saccades elicited from three of the sites (A31, A29 and A27) in the DMFC are shown. Each dotted line represents a saccadic eye movement evoked while the monkey fixated one of five target positions (represented by a circle). A dot inside a circle indicates that saccades were not evoked by the stimulation. The electrical stimulation was delivered as follows: 200 PA, 0.1 ms pulse duration, 150 Hz, 200 ms train duration.

evoked by electrical stimulation are shown for three sites (Fig. 5, right column). The termination zone was located in the hemispace contralateral to the stimulated hemisphere for the rostral site (A3 1). which corresponds to the finding that most units at this site had contraversively directed position bias. For the caudal site (A27), however, the termination zone was located near the central craniotopic position with bias towards the side ipsilateral to the stimulated hemisphere, which corresponds to the finding that most units at the site had ipsiversively directed position bias. Note that the same fixation positions were tested in the recording and stimulation experiments.

Figure 6 illustrates the topographic distribution of position biases along the mediolateral axis (ML3 to ML5) of the right DMFC of

Topography of fixation-related units in the DMFC 1009

Position bias vectors

-20 0 20

ML4 ML5

,-#(Deg.)

-20 0 20 -20 0 20 (oeg.)

FIG. 6. In the top row a plot of position bias vectors is presented for each of three sites in the right DMFC of monkey L. The mediolateral location of the sites was 3, 4 and 5 mm from the midline (ML3, M U and ML5). The rostrocaudal location of sites was 31 mm anterior to the interaural line. In the bottom row, stimulation-evoked saccades elicited from the above sites are shown. See Figure 5 for other details.

monkey L. The position bias vectors of units studied in three sites of the DMFC are shown (Fig. 6, top row). The position bias vectors were directed downwards at the medial DMFC site (ML3) and upwards at the lateral site (ML5). This concurs with the arrangement of termination zones as defined by electrical stimulation of the sites (Fig. 6, bottom row). The termination zone of the medial site (ML3) was located in lower space, while the termination zone of the lateral site (ML5) was located in upper space.

In Figure 7, the mean position bias of units for the horizontal and vertical dimensions is plotted as a function of the rostrocaudal and mediolateral locations of units within the DMFC. For the horizontal dimension, the position bias is plotted as negative for an ipsilateral bias and positive for a contralateral bias (Fig. 7A). For the vertical dimension, the position bias is plotted as negative for a downward bias and positive for an upward bias (Fig. 7B). For all the monkeys studied, the mean position bias of units changed from contralateral to ipsilateral hemispace as the site of unit collection changed from rostra1 to caudal sites of the DMFC. And the mean position bias changed from lower to upper space as the site of unit collection changed from medial to lateral. Experiments on all three monkeys showed a correspondence between the mean position bias of units at sites within the DMFC and the termination zones of those sites as determined by electrical stimulation.

Discussion DMFC unit activity related to visual fixation The current study is in concordance with previous studies of the same area (Bon and Lucchetti, 1992; Schlag et al., 1992), showing that the activity of neurons in the DMFC is modulated by visual fixation. Many of these neurons exhibited tonic activity that was maintained during the whole period of fixation in a preferred region of craniotopic space. This finding suggests that the cells code for positions in space according to craniotopic or body-centred coordin- ates. From the current study, it cannot be determined which of these coordinate systems is utilized, since we did not change the position of the head with respect to the body while recording from the cells. In the electrical stimulation experiments (Tehovnik and Lee, 1993). however, the topographic map of the termination zone did not change with changes in head position, suggesting that the DMFC codes craniotopicall y.

A * 0.5

+left DMFC, A - - - + - left DMFC, L f- -i -.*-right DMFC. <

-0.5 A31 A29 A27 A25 Coordinate from interaural line (mm)

B 0.5 I I

. -leftDMFC,A

. --+-right DMFC, L

J

0

-0.5 I I I I 1 MLZ ML3 ML4 M-5 Coordinate from midline (mm)

FIG. 7. (A) The mean and SE were calculated for the horizontal component of position bias vectors for a number of units (ranging from 7 to 14) collected at a particular rostrocaudal location (between A32 and A25) in the DMFC of three monkeys. The horizontal position bias for a group of units is plotted as function of the rostrocaudal location of those units according to their location with respect to the interaural line. The mediolateral location of the units for monkeys A and Y was between 2 and 3 mm off the midline, and for monkey L it was between 3 and 4 mm off the midline. The data points for monkey A were computed from the same data as shown in Figure 5. All plots were statistically significant by a linear regression analysis (P < 0.01). (B) The mean and SE were calculated for the vertical component of position bias vectors for a number of units (ranging from 6 to 10) collected at a particular mediolateral location (between MLI and ML6) in the DMFC of two monkeys. The vertical position bias for a group of units is plotted as a function of the mediolateral location of those units according to their location with respect to the midline. The rostrocaudal location of the units for monkey A was between 30 and 29 mm anterior to the interaural line, and for monkey L it was 3 1 mm anterior to the interaural line. The data points for monkey L were computed from the same data as shown in Figure 6. All plots were statistically significant by linear regression analysis ( P < 0.01 ).

1010 Topography of fixation-related units in the DMFC

Neurons modulated by visual fixation are not unique to the DMFC. Such cells have been found in the frontal eye fields as well as in the posterior parietal cortex (Bizzi, 1968; Lynch et al., 1977; Sakata er al., 1980; Motter and Mountcastle, 1981; Mountcastle er al., 1981; Andersen and Mountcastle, 1983; Bruce and Goldberg, 1985). Less than 10% of the cells studied in the frontal eye fields were modulated by visual fixation, whereas over 70% were modulated by saccadic eye movements (Bruce and Goldberg, 1985), suggesting that the frontal eye fields are more involved in the mediation of saccadic eye movements than visual fixation. Unlike the frontal eye fields, >50% of cells studied in the posterior parietal cortex were responsive during visual fixation (Motter and Mountcastle, 1981). Many of these cells have visual receptive fields, and the light sensitivity of these cells is modulated by changes in eye position (Andersen, 1987).

In the DMFC it is the fixation-related activity of neurons, rather than their visual receptive field properties, that is most conspicuously influenced by changes in eye position (see also Bon and Lucchetti, 1992; Schlag et al., 1992). Thus, unlike the posterior parietal cortex, which codes a craniotopic representation of visual space (Andersen, 1987), the DMFC may code a craniotopic representation of motor space, i.e. a representation that is in terms of the final position of the eyes in orbit. A craniocentric representation is important not only for acquiring a stable perception of the outside world, but also for generating spatially accurate eye movements [see below; see also Goldberg and Bruce (1990) for another view].

Topography of eye position dependency in the DMFC The neurons within the DMFC are represented topographically according to their position bias, and this representation concurs with the topographic order of termination zones as defined by electrical stimulation (Tehovnik and Lee, 1993). Cells within the rostra1 DMFC respond maximally when a monkey fixates targets in contralateral craniotopic space, cells within the caudal DMFC respond maximally when a monkey fixates targets in ipsilateral craniotopic space, cells within the medial DMFC respond maximally when a monkey fixates targets in lower craniotopic space, and cells within the lateral DMFC respond maximally when a monkey fixates targets in upper craniotopic space. Recently, this topographical representation of the DMFC was investigated in terms of its efferents to the frontal eye fields (Schall et al., 1993). The authors proposed that the efferents mediate a coordinate transformation from a craniotopic to a retinotopic representation for saccade generation.

Coding for position in craniotopic coordinates Experiments have shown that a saccadic eye movement is generated in a space-centred manner, such that the perturbation of eye position is well tolerated once the saccade is programmed (Mays and Sparks, 1980; Schiller and Sandell, 1983). What these experiments indicate is that the ‘desired’ eye position, or the termination position, of a saccade is coded in spatial coordinates (Robinson, 1975), whereby the code for the termination position remains unchanged even when the current eye position is shifted by experimental means.

As yet, the source of such a code has not been identified. The burst neurons in the brainstem code for eye movement rather than eye position (for a review see Fuchs et al., 1985). The burst activity, then, is believed to be transformed into a code for eye position by an integrator in the brainstem (Robinson, 1975; Fuchs et al., 1985). The integrator, however, does not code for the desired eye position, but keeps track of the current eye position. It is unlikely that either the frontal eye fields or superior colliculi code for the desired eye position, because electrical stimulation of these areas evokes saccades

that have constant direction and amplitude independent of initial eye position (Robinson and Fuchs, 1969; Robinson, 1972; Schiller and Stryker, 1972; Bruce et al., 1985). Also, these areas code for eye movement by specifying the direction and amplitude of saccadic eye movements in a form of perisaccadic burst activity (Schiller and Stryker, 1972; Bruce et al., 1985).

Based on our current and previous experiments (Tehovnik and Lee, 1993; Tehovnik et al., 1994). it is conceivable that the DMFC is one area that specifies the termination position of a saccadic eye movement in craniotopic coordinates. Six observations support this hypothesis: (i) the activity of DMFC units is modulated by changes in eye position; (ii) >60% of the units in the DMFC have activity related to visual fixation; (iii) of these units, 44% discharge tonically before the eyes amve on target; (iv) electrical stimulation of a site within the DMFC elicits a saccade that brings the eyes to the termination position encoded by that site; (v) the same stimulation produces inhibition of visually evoked eye movements and holds the eyes at the current position when the eyes are already at the termination position; and (vi) the termination position encoded by a given site, as defined by electrical stimulation, is invariant to changes in head position.

In conclusion, the position tuning of fixation cells within the DMFC is topographically ordered. These fixation cells may encode the future eye position before a saccade is executed in craniotopic coordinates, and they may hold the eyes on target during visual fixation.

Acknowledgements We are grateful to Dr Peter H. Schiller for his helpful comments and support (NIH EY08502). Funding was also provided by a Fairchild and a McDonnell- Pew fellowship to E. J . T.

Abbreviations DMFC FIX 1 FIX2 LED SAC 1 SAC2 TI T2

dorsomedial frontal cortex time period of visual fixation at the first target (TI) time period of visual fixation at the second target (T2) light-emitting diode time period of a saccadic eye movement to the first target (TI) time period of a saccadic eye movement to the second target (T2) first visual target second visual target

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