INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Neurophysiological studies using spatial working memory tasks have revealed that many neurons in the prefrontal cortex exhibit tonic activation during the delay period (delay-period activity) (Funahashi et al. 1989, 1993; Fuster 1973; Fuster and Alexander 1971; Kojima and Goldman-Rakic 1982, 1984; Kubota and Funahashi 1982; Kubota et al. 1974; Niki 1974; Niki and Watanabe 1976; Rainer et al. 1998; Rao et al. 1997; Wilson et al. 1993). Most of this delay-period activity has been shown to have directional selectivity, such that delay-period activity was observed only when visual cues were presented at a particular location in the visual field (Funahashi et al. 1989, 1993; Niki 1974; Niki and Watanabe 1976; Rainer et al. 1998; Rao et al. 1997; Wilson et al. 1993). In addition, delay-period activity was observed only when the monkey performed correctly in the task. When the monkey made an error, delay-period activity either was not observed or was observed but truncated (Funahashi et al. 1989, 1997; Fuster 1973; Niki and Watanabe 1976). Based on these observations, delay-period activity has been considered a neuronal correlate of temporary active storage mechanisms in working memory processes (Funahashi and Kubota 1994; Fuster 1997; Goldman-Rakic 1987, 1995, 1996).

A few studies have analyzed the information encoded by delay-period activity (Funahashi et al. 1993; Niki and Watanabe 1976). Niki and Watanabe (1976) examined the same neuron's delay-period activity while monkeys performed two-choice manual versions of the delayed-response tasks and a two-choice conditional-position task. In the delayed-response tasks, the monkey selected either a right or left or an upper or lower response key after the delay depending on the position where the cue was presented, whereas in the conditional-position task, the monkey selected either a right or left key after the delay depending on whether the cue was presented in an upward or downward position. They found that 78% of delay-period activity encoded the location of the visual cue, whereas the remaining 22% encoded the direction of the response (right or left). Funahashi et al. (1993) also examined delay-period activity while monkeys performed a delayed pro-saccade task and a delayed anti-saccade task. In these tasks, visual cues were presented at the same location. However, the direction of the saccade in the delayed anti-saccade task was opposite the direction in the pro-saccade task. They also found that 70% of delay-period activity encoded the location of the visual cue and the remaining 30% encoded the direction of the saccade. These results indicate that delay-period activity acts as a mechanism for the temporary storage of visual and motor information in working memory processes and that most delay-period activity encodes sensory information.

Working memory is a mechanism for the temporary active storage of information. However, working memory can also be considered a dynamic system that includes mechanisms for processing and integrating information (Baddeley 1986; Funahashi and Kubota 1994; Miyake and Shah 1999). Understanding how information is processed and integrated is essential for understanding neuronal mechanisms in working memory. The finding that about 70% of delay-period activity encodes the location of the visual cue, whereas about 30% encodes the direction of the saccade suggests that processing and integrating information to produce motor output occur in the prefrontal cortex. To elucidate the mechanism for processing and integrating information, it is crucial to identify what kind of information is encoded by each task-related activity. Most previous studies have described the "differential" nature of task-related activity, depending on differences in stimuli or motor responses (Funahashi et al. 1989, 1993; Niki 1974; Niki and Watanabe 1976; Quintana et al. 1988; Rainer et al. 1998; Rao et al. 1997; Wilson et al. 1993). However, the type of information that is encoded by each task-related activity has not been considered. Therefore in the present experiment, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two types of oculomotor delayed-response tasks. In the standard oculomotor-delayed response (ODR) task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90° clockwise from the cue location after the 3-s delay. In the latter task, monkeys were required to transform visual input to motor output to perform correct eye movement. In addition, by comparing task-related activity between these two tasks, we can identify whether task-related activity encodes the location of the visual cue or the direction of the saccade. Therefore we can discuss how the prefrontal cortex participates in transformation processes from visual input to motor output.

A preliminary report of this study has been published in abstract form (Takeda et al. 1999a,b). This experiment was conducted as part of the Cooperation Research Program of the Primate Research Institute, Kyoto University (1998-2000).

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subjects and apparatus

Two rhesus monkeys (monkey M, 3.6 kg; monkey N, 3.8 kg) were used in this study. Each monkey was housed individually in a home cage. Monkeys were deprived of water in their home cages but could obtain their daily requirement of water in the laboratory as a reward. To ensure each monkey's condition, body weight and water intake were measured daily. All experiments were conducted according to the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. This experiment was approved by the Animal Research Committee of the Faculty of Integrated Human Studies, Kyoto University.

During training and recording sessions, the monkey sat in a primate chair in a dark room. The monkey's head was fixed by a head-restraining instrument. The monkey faced a 21-in color monitor (E77F, NANAO) on which a fixation point and visual cues were presented. The monitor was placed 30 cm away from the monkey's face. The monkey's eye positions were monitored by the magnetic search coil technique (Robinson 1963). Two laboratory computers (PC-386GE and PC-486HX, Epson) controlled the monkey's behavior, presented visual stimuli on the monitor, recorded neuronal activities, and monitored eye movements.

Behavioral tasks

In the present study, we used two types of ODR tasks; an ODR task and a rotatory oculomotor delayed-response (R-ODR) task. By analyzing neuronal activity in both tasks, we could identify whether task-related activity encoded the location of the visual cue or the direction of the saccade.

ODR TASK. In this task, the monkey was required to make a saccade to the location where the cue had been presented after a 3-s delay. The temporal sequence of this task is illustrated in Fig. 1A (top). After a 5-s intertrial interval (ITI), a fixation point (FP; white circle, 0.5° in visual angle) was presented at the center of the monitor. If the monkey continued to look at the FP for 1 s, a visual cue (white circle, 1° in visual angle) was presented for 0.5 s at one of eight predetermined locations around the FP. The monkey was required to maintain fixation on the FP throughout the 0.5-s cue period and subsequent 3-s delay period. At the end of the delay period, the FP was extinguished. This was the go signal for the monkey to make a saccade within 0.35 s (the response period) to the location where the visual cue had been presented. If the monkey performed the correct eye movement, it was rewarded by a drop (about 0.2 ml) of water. To estimate whether the monkey's eye movement was correct or not, we set a square window (4-6° in visual angle) around the target location and considered that the monkey performed a correct saccade if its eye position fell within this window. If the monkey broke fixation during the cue or delay period, if the monkey failed to perform a saccade within the 0.35-s response period, or if the eye movement didn't fall within the correct window, the trial was aborted immediately without reward and the next trial began. The visual cue was presented at one of eight predetermined peripheral locations (Fig. 1B, top). Its eccentricity was 17°. The location of the visual cue was randomized over trials.

View larger version (19K): [in this window] [in a new window]   Fig. 1. Diagrams of 2 types of oculomotor-delayed response (ODR) tasks and cue locations. A: temporal sequences of task events. Top: a standard ODR task. The monkey was required to make a saccade to the location where the visual cue had been presented. Bottom: a rotatory ODR (R-ODR) task. The monkey was required to make a saccade to 90° clockwise from the location where the visual cue had been presented. B: locations of the visual cue in each task. FP, fixation point. The eccentricity of cue locations was 17°.

R-ODR TASK. In this task, the monkey was required to make a saccade 90° clockwise from the location where the visual cue had been presented. The temporal sequence of this task is illustrated in Fig. 1A (bottom). After a 5-s ITI, the FP (a white cross, 0.5° in visual angle) was presented at the center of the monitor. If the monkey continued to look at the FP for 1 s, the visual cue (white circle, 1° in visual angle) was presented for 0.5 s at one of four predetermined locations around the FP. The monkey was required to maintain fixation on the FP throughout the 0.5-s cue period and subsequent 3-s delay period. At the end of the delay period, the FP was extinguished. This was the go signal for the monkey to make a saccade within 0.35 s (the response period) in a direction 90° clockwise from the location where the visual cue had been presented. If the monkey performed the correct eye movement, it was rewarded by a drop (about 0.2 ml) of water. We used the same square window around the target location and the same criterion to determine correct saccades as was used in the ODR task. If the monkey broke fixation during the cue or delay period, if the monkey failed to perform a saccade within the 0.35-s response period, or if its eye movement didn't fall within the correct window, the trial was aborted immediately without reward and the next trial began. The visual cue was presented at one of four predetermined peripheral locations (Fig. 1B, bottom). Its eccentricity was 17°. The location of the visual cue was randomized over trials.

Surgical procedure

We first performed surgery under aseptic conditions to implant an eye coil to monitor eye movements and a stainless steel device to restrain the monkey's head during the experiments. The monkey was first immobilized by injecting ketamine intramuscularly and then anesthetized by intravenous injection of pentobarbital sodium (25 mg/kg). Using the technique described by Judge et al. (1980), the eye coil was implanted under the conjunctiva in one eye. To restrain the monkey's head during the experiment, a head-restraining device made of stainless steel was implanted on the skull. To reinforce the implantation of the head-restraining device, stainless steel bolts were implanted on the skull. The connector for the eye coil, the head-restraining device, and the stainless steel bolts were fixed to the skull with dental acrylic.

After we finished the monkey's training, we performed a second surgery. In this surgery, we implanted a stainless steel cylinder to record neuronal activities from the prefrontal cortex. The monkey was first immobilized by injecting ketamine intramuscularly and then anesthetized by intravenous injection of pentobarbital sodium (25 mg/kg). We fixed the monkey's head in the stereotaxic apparatus and exposed a part of the skull. We made a small hole (20 mm in diameter) using a trephine in the skull at the area corresponding to the principal sulcus as estimated by stereotaxic coordinates (30.0 mm anterior from the interaural plane and 15.0 mm lateral from the midline) and attached the stainless steel cylinder to the hole. Some additional stainless steel bolts were implanted on the skull and fixed to the cylinder by dental acrylic. After each surgery, the monkey was administered antibiotics (Cephalosporin, FUJISAWA) for a few days to prevent infection. The monkey was given a full amount of food and water during the recovery period.

Recording single-neuron activity

After the monkey fully recovered from the second surgery, we started recording single-neuron activity from the cortex within and surrounding the principal sulcus while the monkey performed both tasks. In the recording sessions, the monkey performed each task in blocks of 100-150 trials. After we isolated single-neuron activity, we usually recorded the neuron's activity while the monkey performed the R-ODR task and then recorded its activity while the monkey performed the ODR task. Single-neuron activity was recorded by glass-coated elgiloy microelectrodes (0.5-1.5 M at 1 kHz). Raw neuron activity was amplified using an amplifier (DAM80, World Precision Instruments) and monitored using an oscilloscope (SS-7802, Iwatsu Electronics). At the same time, we isolated single-neuron activity using a window discriminator (DIS-1, BAK Electronics) and monitored its output using an oscilloscope. The output of the window discriminator was input to the computer (PC-386GE, Epson) and stored together with task events on magnetic media. We also stored raw neuron activities, task events, and horizontal and vertical eye movements on magnetic tapes using a data recorder (PC-108 M, Sony Precision Technology).

Data analysis

To examine whether the recorded neuron exhibited task-related activity (cue-period activity, delay-period activity, or response-period activity), we made rasters and histograms triggered at three alignment points (the onset of the cue period, the end of the delay period, and the onset of reward delivery) for each cue condition in both tasks. Using these rasters and histograms, we first visually inspected whether or not the neuron had task-related activity. Then we performed statistical analysis to identify characteristics of task-related activity.

First, to estimate the neuron's baseline discharge rate, we calculated the mean discharge rate during the 1-s fixation period for each cue condition. For cue-period activity, we calculated the mean discharge rate during the 300-ms period (from 100 to 400 ms after the onset of the visual cue) for each cue condition. If the mean discharge rate during the cue period differed significantly from the mean discharge rate during the fixation period by the Mann-Whitney U test (P < 0.05), we considered that this neuron exhibited cue-period activity. Similarly, for delay- and response-period activity, we calculated either the mean discharge rate during the 3-s delay period for each cue condition or the mean discharge rate during the 300-ms response period (150 ms before and after the period when the peak activity was observed) for each cue condition. If the mean discharge rate during either the delay period or the response period differed significantly from the mean discharge rate during the 1-s fixation period by the Mann-Whitney U test (P < 0.05), we considered that the neuron exhibited delay-period activity or response-period activity, respectively. In addition, we classified response-period activity into two groups (pre- and postsaccadic activity) based on whether the initiation of response-period activity preceded the initiation of saccadic eye movements. These statistical tests were run independently for each task-related activity.

Previous studies have shown that most neurons with cue-period activity, delay-period activity, or response-period activity exhibit directional selectivity during the ODR task (Funahashi et al. 1989-1991). Therefore we also examined directional selectivity for task-related activity. In the present study, we first examined the difference in the mean discharge rates among all cue conditions for each task-related activity by one-way ANOVA. We considered that the task-related activity had directional selectivity if this difference was significant (P < 0.05). To estimate the best direction of task-related activity, we made a tuning curve for each task-related activity. The tuning curve was made from the mean discharge rate under each cue condition based on its best fit to the Gaussian function
where f (d) is the discharge rate as a function of the visual cue location d. The constants can be interpreted as follows: B indicates the discharge rate during the fixation period, R indicates the discharge rate at the best direction, D indicates the direction associated with the maximum discharge rate, and Td is an index of the tuning width. We considered D to be the best direction for task-related activity. We used D_ODR for the best direction in the ODR task and D_R-ODR for the best direction in the R-ODR task.

To identify whether task-related activity encodes the location of the visual cue or the direction of the saccade, we compared the cue conditions under which the maximum task-related activity was observed in the ODR and R-ODR tasks for the same neuron. Since the location of the visual cue and the direction of the saccade are different in the R-ODR task, we use the term "cue condition" to describe trial conditions in the ODR and R-ODR tasks. Thus the 0° cue condition indicates that the visual cue was presented at the 0° location in both tasks, while the direction of the saccade was 0° in the ODR task but 270° in the R-ODR task. We also use the term "max cue condition" to describe the cue condition under which the maximum task-related activity was observed. We determined the max cue condition of task-related activity in the ODR task and the max cue condition of the same task-related activity in the R-ODR task. We then compared the max cue conditions in the two tasks. In the ODR task, the location of the visual cue and the direction of the saccade were the same, whereas in the R-ODR task, the direction of the saccade was 90° clockwise from the location of the visual cue. Therefore if the max cue conditions of task-related activity were the same in the two tasks, this task-related activity would be considered to encode the location of the visual cue. On the other hand, if the max cue condition in the R-ODR task was 90° counterclockwise from that in the ODR task, this task-related activity would be considered to encode the direction of the saccade. In the present experiment, eight cue locations were used in the ODR task, whereas only four cue locations were used in the R-ODR task. Therefore if the max cue condition in the R-ODR was 45° clockwise from the max cue condition in the ODR task, this activity would be considered to encode the location of the visual cue. Similarly, if the max cue condition in the R-ODR task was 135° counterclockwise from the max cue condition in the ODR task, this activity would be considered to encode the direction of the saccade. If the max cue condition in the R-ODR task was 45° counterclockwise from the max cue condition in the ODR task, it would be difficult to determine whether the task-related activity encoded the location of the visual cue or the direction of the saccade. Therefore we compared the best directions of tuning curves for this task-related activity in the two tasks. If the difference between the best directions in the two tasks was less than 45°, we considered that this task-related activity encoded the location of the visual cue. On the other hand, if the difference between the best directions in the two tasks was more than 45°, we considered that this task-related activity encoded the direction of the saccade.

In some neurons, the max cue condition of task-related activity in the R-ODR task was more than 135° counterclockwise from the max cue condition in the ODR task. For these neurons, we could not determine whether this task-related activity encoded the location of the visual cue or the direction of the saccade. Therefore we excluded these neurons from this analysis.

Histological examinations

At the end of the experiment, we made electrolytic lesions by passing a positive current through the elgiloy microelectrode at the four corners of the recording area to identify the recording site during histological examinations. Monkeys were deeply anesthetized by injecting an overdose of pentobarbital sodium (45-50 mg/kg) intravenously. The brain was first perfused by saline, and then by 10% formalin solution with 2% potassium ferrocyanide. The brain was removed from the skull and stored in 10% formalin solution with 30% sucrose. The brain was cut into 100-µm-thick coronal sections, and each section was stained with cresyl violet.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Behavioral performance

In the present experiment, the two monkeys performed both the ODR and R-ODR tasks at a correct performance rate of more than 85% throughout the recording sessions. Figure 2 shows distributions of end points of saccades in two tasks for the two monkeys. In the ODR task, the end points of saccades made distinct clusters close to each of the eight targets (Fig. 2, A and C). Similarly, in the R-ODR task, the end points of saccades also made distinct clusters close to each of the four targets (Fig. 2, B and D). Since monkeys performed memory-guided saccades during the response period, end points of saccades were often displaced a little from the actual target location. To quantify saccade accuracies in each task condition for each monkey, we calculated means of distances between saccade ends and target locations. For monkey M, the average displacement from the target location was 3.3° in ODR task and 5.5° in R-ODR task. For monkey N, the average displacement from the target location was 3.8° in ODR task and 4.7° in R-ODR task. There was no significant difference in the accuracy of saccades during each task between two monkeys. In addition, the saccade latencies showed no difference in two task conditions [monkey M, 289.9 ± 20.0 (SD) ms in ODR task and 284.1 ± 22.2 ms in R-ODR task; monkey N, 294.5 ± 17.0 ms in ODR task and 281.9 ± 18.9 ms in R-ODR task].

View larger version (16K): [in this window] [in a new window]   Fig. 2. Distributions of end points of saccades during the ODR and R-ODR tasks in 2 monkeys. , the end point of each saccade performed at the response period. , locations of the visual cue. Sampled data were based on 5 recording sessions for monkey M and 4 recording sessions for monkey N. The eccentricity of cue locations was 17°.

Database

We recorded the activities of 304 neurons (monkey M, n = 96; monkey N, n = 208) from the cortex within and surrounding the principal sulcus. The recording areas of neurons that exhibited task-related activity are illustrated in Fig. 3. Most of these neurons were sampled from the middle and posterior part of the principal sulcal area. The frontal eye field was not included in the recording area. The distributions of neurons that exhibited either cue-, delay-, or response-period activity overlapped. We could not find any topographic distributions of task-related activities.

View larger version (10K): [in this window] [in a new window]   Fig. 3. Surface plots of locations of neurons that showed task-related activity. , the location of task-related neurons. PS, principal sulcus; AS, arcuate sulcus.

Among these 304 neurons, activities were recorded during both tasks in 216 neurons, only during the ODR task in 35 neurons, and only during the R-ODR task in 53 neurons. As a result, the activities of 251 neurons were recorded during the ODR task and those of 269 neurons were recorded during the R-ODR task. The numbers of neurons with task-related activity and directional selectivity are summarized in Table 1. The characteristics of task-related activity and directional selectivity were similar between the two tasks.

Of the 216 neurons that were recorded during both tasks, 163 neurons (75%) exhibited task-related activity for at least one task event. These neurons were classified into two groups based on whether the neuron exhibited task-related activity for at least one task event during both tasks. One hundred twenty one neurons (74%) exhibited task-related activity for at least one task event during both tasks. However, the remaining neurons exhibited task-related activity only during ODR performance (n = 19), only during R-ODR performance (n = 18), or during different events in the two tasks (n = 5).

Neurons that exhibited the same task-related activity during both the ODR and R-ODR tasks

In the present study, we tried to understand what kind of information each task-related activity encoded. Therefore we compared the max cue conditions for the same task-related activity between the ODR and R-ODR tasks in the same neuron. Of the 216 neurons recorded in both tasks, we analyzed 121 neurons that exhibited task-related activity for at least one task event during the performance of both tasks in detail. Among these 121 neurons, 43, 60, 70, and 2 exhibited cue-period activity, delay-period activity, response-period activity, and fixation-related activity, respectively (Table 2). Fixation-related activity is a phasic response to the appearance of the fixation point.

We first examined whether or not the task difference affected spontaneous background discharge rates since White and Wise (1999) found rule-dependent neuronal activity in the prefrontal cortex. We selected mean discharge rates during the fixation period as background discharge rates because the monkey's behavior was exactly the same in the two tasks. In 121 neurons, we calculated the mean discharge rates during the 1-s fixation period in both the ODR and R-ODR tasks, respectively, and compared these rates between the two tasks. Figure 4 shows a scattergram of mean discharge rates in the fixation period. The correlation coefficient calculated from this scattergram is 0.737. The mean discharge rates during the ODR task and R-ODR task were 9.21 ± 6.76 spikes/s (n = 121, mean ± SD) and 9.27 ± 7.47 spikes/s (n = 121), respectively. Background activity during the ODR task was not significantly different from that during the R-ODR task (Wilcoxon signed-rank test, P = 0.94). Therefore these results indicate that there was no task-dependent difference in background discharge rates in the present experiment.

View larger version (18K): [in this window] [in a new window]   Fig. 4. Scattergram of mean discharge rates during the fixation period in the ODR and R-ODR tasks. , each neuron's mean discharge rate during the 1-s fixation period in the 2 tasks. The correlation coefficient is 0.737. The mean discharge rates during the fixation period in the 2 tasks were not significantly different (Wilcoxon signed-rank test, P = 0.94, n = 121).

Cue-period activity

Of 43 neurons exhibited cue-period activity in both tasks, 41 (95%) exhibited directional cue-period activity and 2 exhibited omni-directional cue-period activity (Table 3). Figure 5 shows an example of a neuron with directional cue-period activity. In the ODR task, this neuron showed significant cue-period activity whenever visual cues were presented on the left side of the visual field (Fig. 5A). The maximum (max) cue condition of cue-period activity was 225° in the ODR task. In the R-ODR task, significant cue-period activity was also observed when the visual cues were presented at the 90° and 180° locations (Fig. 5B). The max cue condition of cue-period activity was 180° in the R-ODR task. For this neuron's cue-period activity, the max cue conditions were 225° in the ODR task and 180° in the R-ODR task. Therefore this neuron's directional cue-period activity was considered to encode the location of the visual cue. In addition, the best directions of cue-period activity based on the tuning curves were 177.2° in the ODR task and 155.9° in the R-ODR task. The best directions of cue-period activity were almost identical in the two tasks. This result confirms that this neuron's directional cue-period activity encodes the location of the visual cue.

View larger version (40K): [in this window] [in a new window]   Fig. 5. Directional cue-period activity encoding the location of the visual cue. A: neuron activity during the ODR task. This neuron exhibited significant cue-period activity whenever the visual cues were presented on the left side of the visual field (90°, z = 2.86, P < 0.01; 135°, z = 4.49, P < 0.001; 180°, z = 4.30, P < 0.001; 225°, z = 4.92, P < 0.001). The max cue condition was 225°. B: neuron activity during the R-ODR task. Significant cue-period activity was observed when the visual cues were presented at the 90° (z = 2.97, P < 0.01) and 180° (z = 5.32, P < 0.001) locations. The max cue condition was 180°. The visual cues were randomly presented at 1 of 8 or 4 locations indicated in the central diagram during the ODR task or the R-ODR task, respectively. All cue eccentricities were 17° and the histogram binwidth was 30 ms. The numbers at the top left of each figure indicate the location of the visual cue (left) and the direction of the saccade (right), respectively. C, cue period; D, delay period; R, response period.

Figure 6 shows two other examples of neurons in which the best directions of cue-period activity were almost identical in the two tasks. In neuron m101 (Fig. 6A), the best directions were 347° in the ODR task and 343.4° in the R-ODR task. In neuron m080 (Fig. 6B), the best directions of cue-period activity were 100.7° in the ODR task and 120.1° in the R-ODR task. These results indicate that the maximum cue-period activity of these neurons was observed with the same cue condition in both tasks, regardless of the direction of saccades. Therefore we could conclude that the directional cue-period activity of these neurons encodes the location of the visual cue.

View larger version (19K): [in this window] [in a new window]   Fig. 6. Comparisons of tuning curves of cue-period activity in the ODR task and R-ODR task. Each symbol on the tuning curve represents the mean discharge rate during the cue period for each cue condition in the 2 tasks. The mean discharge rate for each cue condition was calculated by the discharge rate during a 300-ms period (from 100 to 400 ms after the onset of the visual cue). A: neuron m101. The best directions were 347° in the ODR task (, R2 = 0.918) and 343.4° in the R-ODR task (- - -, R2 = 0.978). B: neuron m080. The best directions were 100.7° in the ODR task (, R2 = 0.702) and 120.1° in the R-ODR task (- - -, R2 = 0.985).

We compared the best directions (D) of cue-period activity between the two tasks for all neurons that exhibited directional cue-period activity. Figure 7A shows the distributions of the differences between the best directions (D_R-ODR-D_ODR) in the two tasks. With regard to 90% of cue-period activity, the differences between the best directions in the two tasks were distributed between 45° and 45°. The mean difference between the best directions in the two tasks was 7.9 ± 28.0°. These results support the notion that cue-period activity encodes the location of the visual cue.

View larger version (13K): [in this window] [in a new window]   Fig. 7. A: distribution of the difference between the best directions in cue-period activity in the 2 tasks. The difference between the best directions (DR-ODR-DODR) was distributed from 45° to 67.5° (7.9 ± 28.0°; n = 41). B: comparison of peak discharge rates of cue-period activity in the 2 tasks. , each neuron's mean discharge rate during the cue period. The correlation coefficient was 0.796. There was no significant difference in peak discharges between the 2 tasks (Wilcoxon signed-rank test, P = 0.55, n = 26).

To examine whether or not the magnitude of cue-period activity was task-dependent, we compared the peak discharge rates during the cue period in the two tasks for 26 neurons that exhibited good Gaussian fitting. Figure 7B shows a scattergram of peak discharge rates of cue-period activity in the two tasks. The mean peak discharge rates were 27.22 ± 17.46 spikes/s (n = 26) in the ODR task and 25.54 ± 14.13 spikes/s (n = 26) in the R-ODR task. The mean peak discharge rates were not significantly different between the two tasks (Wilcoxon signed-rank test, P = 0.55). Therefore this result indicates that the magnitude of cue-period activity was similar between the two tasks for most of the neurons.

Delay-period activity

Of 60 neurons exhibited delay-period activity in both tasks, 56 (93%) exhibited directional delay-period activity and 4 (7%) exhibited omni-directional delay-period activity (Table 3). For neurons with directional delay-period activity, we compared the max cue conditions of delay-period activity and the best directions calculated from tuning curves of delay-period activity in the two tasks. As a result, directional delay-period activity was classified mainly into two groups. In one group, delay-period activity encoded the location of the visual cue, whereas in the other group, delay-period activity encoded the direction of the saccade. In one neuron, the max cue condition of delay-period activity in the R-ODR task was more than 135° counterclockwise from the max cue condition in the ODR task, and we could not determine whether task-related activity encoded the location of the visual cue or the direction of the saccade for this neuron.

Delay-period activity encoding the location of the visual cue

In 48 (86%) of 56 neurons with directional delay-period activity, delay-period activity encoded the location of the visual cue. Figure 8 shows an example of directional delay-period activity that encoded the location of the visual cue. In the ODR task, this neuron exhibited significant delay-period activity when visual cues were presented at the 270° and 315° locations (Fig. 8A). The max cue condition of delay-period activity was 315° in the ODR task. In the R-ODR task, significant delay-period activity was observed when the visual cue was presented at the 270° location (Fig. 8B). The max cue condition of delay-period activity was 270° in the R-ODR task. The max cue conditions of delay-period activity were 315° in the ODR task and 270° in the R-ODR task. Therefore this neuron's directional delay-period activity appears to encode the location of the visual cue. In addition, the best direction of delay-period activity based on the tuning curve was 297.0° in the ODR task and 269.7° in the R-ODR task. The best directions of delay-period activity were almost identical in the two tasks. Because the directions of saccades that were performed for the same cue condition were different in the two tasks, this result also supports the notion that this neuron's directional delay-period activity encodes the location of the visual cue rather than the direction of the saccade.

View larger version (43K): [in this window] [in a new window]   Fig. 8. Directional delay-period activity encoding the location of the visual cue and directional postsaccadic activity encoding the direction of the saccade. A: neuron activity during the ODR task. This neuron exhibited significant delay-period activity when the visual cues were presented at the 270° (z = 5.17, P < 0.001) and 315° (z = 4.47, P < 0.001) locations and significant postsaccadic activity when the visual cues were presented at the 135° (z = 5.23, P < 0.001) location. The max cue conditions were 315° for delay-period activity and 135° for postsaccadic activity. B: neuron activity during the R-ODR task. Significant delay-period activity was observed when visual cues were presented at the 270° (z = 4.50, P < 0.001) location (the max cue condition of delay-period activity) and significant postsaccadic activity was observed when visual cues were presented at the 270° (z = 4.62, P < 0.001) location (the max cue condition of postsaccadic activity). C: neuron activity aligned at the onset of reward delivery in the 2 tasks. Top: postsaccadic activity at the 135° cue condition during the ODR task. Bottom: postsaccadic activity at the 270° cue condition during the R-ODR task. All cue eccentricities were 17°, and the histogram binwidth was 30 ms for A and B and 20 ms for C. The numbers at the top left of each figure indicate the location of the visual cue (left) and the direction of the saccade (right).

The directional tuning of delay-period activity in the ODR and R-ODR tasks is compared in Fig. 9. Two examples show tuning curves of delay-period activity in which the best directions in the two tasks were almost identical. For neuron m090, the best directions were 57.7° in the ODR task and 56.6° in the R-ODR task. For neuron n134, the best directions were 19.4° in the ODR task and 38.6° in the R-ODR task. In these neurons, either the best directions of delay-period activity in the two tasks were almost identical or the difference between the best directions in the two tasks was less than 45°. Figure 10A shows the distributions of the difference between the best directions in the two tasks (D_R-ODR-D_ODR) for all directional delay-period activity. In 86% of neurons with directional delay-period activity, the differences between the best directions in the two tasks were between 45° and 45°. In these neurons, the mean difference between the best directions in the two tasks was 2.9 ± 24.1° (n = 48). Therefore these findings indicate that the directional delay-period activity of these neurons apparently encodes the location of the visual cue.

View larger version (21K): [in this window] [in a new window]   Fig. 9. Comparison of tuning curves of delay-period activity in the ODR and R-ODR tasks. Two examples of neurons in which the best directions of delay-period activity in the 2 tasks were almost identical or only slightly different. A: neuron m090. The best directions were 57.7° in the ODR task (, R2 = 0.936) and 56.6° in the R-ODR task (- - -, R2 = 0.978). B: neuron n134. The best directions were 19.4° in the ODR task (, R2 = 0.929) and 38.6° in the R-ODR task (- - -, R2 = 0.998).

View larger version (13K): [in this window] [in a new window]   Fig. 10. A: distribution of differences between the best directions in delay-period activity in the 2 tasks. The differences between the best directions (DR-ODR-DODR) were distributed from 45° to 180.0°. The mean difference in best directions was 2.9 ± 24.1° (n = 48, mean ± SD) for neurons encoding the location of the visual cue and 95.9 ± 35.5° (n = 7) for neurons encoding the direction of saccade. B: comparison of peak discharge rates of delay-period activity in the 2 tasks. The correlation coefficient was 0.932. There was no significant difference in peak discharge rates between the 2 tasks (Wilcoxon signed-rank test, P = 0.25, n = 32).

Delay-period activity encoding the direction of the saccade

In 7 (13%) of 56 neurons with directional delay-period activity, delay-period activity encoded the direction of saccadic eye movement. Figure 11 shows an example of directional delay-period activity that encoded the direction of the saccade. In the ODR task, this neuron exhibited significant delay-period activity when the visual cues were presented at the 0° and 90° locations (Fig. 11A). The max cue condition of delay-period activity was 0° in the ODR task. In the R-ODR task, significant delay-period activity was observed when the visual cue was presented at the 90° location (Fig. 11B). The max cue condition of delay-period activity was 90° in the R-ODR task. The max cue conditions were 0° in the ODR task and 90° in the R-ODR task. In the ODR task, the location of the visual cue and the direction of the saccade were the same, whereas in the R-ODR task, the direction of the saccade was 90° clockwise from the location of the visual cue. Therefore this neuron's directional delay-period activity was considered to encode the direction of the saccade. In addition, the best direction of delay-period activity based on the tuning curve was 1.7° in the ODR task and 68.7° in the R-ODR task, for a difference of about 70°. This result also supports the notion that the directional delay-period activity of this neuron encodes the direction of the saccade.

View larger version (38K): [in this window] [in a new window]   Fig. 11. Directional delay-period activity encoding the direction of the saccade. A: neuron activity during the ODR task. This neuron exhibited significant delay-period activity when visual cues were presented at the 0° (z = 4.39, P < 0.001) and 90° (z = 3.18, P < 0.01) locations. The max cue condition was 0°. B: neuron activity during the R-ODR task. Significant delay-period activity was observed when visual cues were presented at the 90° (z = 4.63, P < 0.001) location. The max cue condition was 90°. All cue eccentricities were 17° and the histogram binwidth was 30 ms. The numbers at the top left of each figure indicate the location of the visual cue (left) and the direction of the saccade (right).

Figure 10A shows distributions of the difference between the best directions in the two tasks for all directional delay-period activity. In only seven neurons (13%), the differences between the best directions in the two tasks (D_R-ODR-D_ODR) were distributed between 45° and 135°. The mean difference between the best directions was 95.9 ± 35.5° (n = 7). Thus these neurons exhibited maximum delay-period activity when the monkey performed saccades to a certain direction, regardless of where the visual cues were presented. Therefore the directional delay-period activity of these neurons is considered to encode the direction of the saccade.

Comparison of peak activity in the ODR and R-ODR tasks

To examine whether or not the magnitude of delay-period activity was task-dependent, we compared the peak discharge rates of delay-period activity between the two tasks for 32 neurons that exhibited good Gaussian fitting. Figure 10B is a scattergram of peak discharge rates of delay-period activity in the two tasks. The mean peak discharge rates were 13.41 ± 8.79 spikes/s (n = 32) in the ODR task and 14.03 ± 8.61 spikes/s (n = 32) in the R-ODR task, and this difference was not significant (Wilcoxon signed-rank test, P = 0.25). Therefore this result indicates that the magnitude of delay-period activity was not task dependent.

Response-period activity

Of 70 neurons exhibited response-period activity in both tasks, 59 exhibited postsaccadic activity, 10 exhibited presaccadic activity, and 1 exhibited both activities (Table 3). Seventy-eight percent of the neurons with postsaccadic activity (n = 47) showed directional selectivity and the remaining 22% (n = 13) showed omni-directional activity. All of the neurons (11/11) with presaccadic activity showed directional selectivity (Table 3). For neurons that exhibited directional response-period activity, we compared the max cue conditions and the best directions calculated from tuning curves for response-period activity in the ODR and R-ODR tasks. As a result, directional response-period activity was classified into four groups. In the first group (n = 33), response-period activity encoded the direction of the saccade. In the second group (n = 20), response-period activity encoded the location of the visual cue. In the third group (n = 2), directional response-period activity was observed in the ODR task, but omni-directional activity was observed in the R-ODR task. In the fourth group (n = 3), we could determine the max cue conditions and best directions for response-period activity in both tasks. However, the max cue condition for response-period activity in the R-ODR task was more than 135° counterclockwise from the max cue condition in the ODR task.

Response-period activity encoding the direction of the saccade

Among the 57 neurons that exhibited directional response-period activity, 33 (58%) showed activity that encoded the direction of the saccade. Of 33 neurons, 88% (n = 29) exhibited postsaccadic activity and the remaining 12% (n = 4) exhibited presaccadic activity. Figure 8 shows an example of postsaccadic activity that encoded the direction of the saccade. In the ODR task, this neuron exhibited significant postsaccadic activity in trials in which the visual cues were presented at the 135° location (Fig. 8A). The max cue condition for postsaccadic activity was 135° in the ODR task. In the R-ODR task, significant postsaccadic activity was observed when the visual cues were presented at the 270° location (Fig. 8B). The max cue condition for postsaccadic activity was 270° in the R-ODR task. In the ODR task, the location of the visual cue and the direction of the saccade were the same, whereas in the R-ODR task, the direction of the saccade was 90° clockwise from the location of the visual cue. In this example, the max cue condition was 135° in the ODR task and 270° in the R-ODR task. Therefore this neuron's directional postsaccadic activity is considered to encode the direction of the saccade. The best directions for postsaccadic activity calculated from the tuning curve were 134.9° in the ODR task and 242.7° in the R-ODR task. The difference between the best directions in the two tasks was 107.8°, which is close to 90°. This result confirms that this neuron's directional postsaccadic activity encodes the direction of the saccade.

Figure 12 shows other examples of presaccadic activity (n171) and postsaccadic activity (m070). The best directions were 78.6° in the ODR task and 164.7° in the R-ODR task for neuron n171 and 134.9° in the ODR task and 242.7° in the R-ODR task for neuron m070. In these neurons, the differences between the best directions in the two tasks were approximately 90° (86.1° for neuron n171 and 107.8° for neuron m070). Therefore the directional activity of these neurons is thought to encode the direction of the saccade.

View larger version (20K): [in this window] [in a new window]   Fig. 12. Comparison of tuning curves of pre- and postsaccadic activity in the ODR and R-ODR tasks. Two examples of neurons in which pre- and postsaccadic activity encoded the direction of the saccade. A: neuron n171. The best directions were 78.6° in the ODR task (, R2 = 0.974) and 164.7° in the R-ODR task (- - -, R2 = 0.999). B: neuron m070. The same neuron as shown in Fig. 8. The best directions were 134.9° in the ODR task (, R2 = 0.936) and 242.7° in the R-ODR task (- - -, R2 = 0.998).

Figure 13A show distributions of the difference between the best directions in the two tasks (D_R-ODR-D_ODR) for all directional response-period activity. In 58% of these neurons (33/57), the differences between the best directions in the two tasks (D_R-ODR-D_ODR) were distributed between 45° and 135°. For these neurons, the mean difference between the best directions in the two tasks was 94.8 ± 22.5° in presaccadic activity (n = 4) and 99.8 ± 33.5° in postsaccadic activity (n = 29).

View larger version (18K): [in this window] [in a new window]   Fig. 13. A: distribution of differences between the best directions in response-period activity in the 2 tasks. The differences between the best directions (DR-ODR-DODR) were distributed from 90° to 202.5°. The mean difference between best directions was 12.4 ± 26.5° (presaccadic activity, n = 5) and 3.84 ± 34.9° (postsaccadic activity, n = 15) for neurons encoding the location of the visual cue, and 94.8 ± 22.5° (presaccadic activity, n = 4) and 99.8 ± 33.5° (postsaccadic activity, n = 29) for neurons encoding the direction of the saccade. B: comparison of peak discharge rates of response-period activity in the 2 tasks. The correlation coefficients were 0.546 for presaccadic activity and 0.66 for postsaccadic activity. There were no significant differences between the peak discharge rates of either pre- or postsaccadic activity in the 2 tasks (presaccadic activity, Wilcoxon signed-rank test, P = 0.66, n = 6; postsaccadic activity, Wilcoxon signed-rank test, P = 0.99, n = 21).

Response-period activity encoding the location of the visual cue

Among the 57 neurons that exhibited directional response-period activity, 20 (35%) showed activity that encoded the location of the visual cue. Of these 20 neurons, 15 (75%) exhibited postsaccadic activity and 5 (25%) exhibited presaccadic activity. Figure 14 shows an example of presaccadic activity that encoded the location of the visual cue. In the ODR task, this neuron exhibited significant presaccadic activity when the visual cues were presented at the 0°, 45°, 225°, and 270° locations (Fig. 14A). The max cue condition for presaccadic activity was 270° in the ODR task. In the R-ODR task, significant presaccadic activity was observed when the visual cues were presented at the 270° location (Fig. 14B). The max cue condition for presaccadic activity was 270° in both the R-ODR and ODR tasks, indicating that the directional presaccadic activity of this neuron encodes the location of the visual cue. The best directions for presaccadic activity calculated from the tuning curves were 256.4° in the ODR task and 283.6° in the R-ODR task. The best directions for presaccadic activity were almost the same in the two tasks. This result confirms that the directional presaccadic activity of this neuron encodes the location of the visual cue.

View larger version (42K): [in this window] [in a new window]   Fig. 14. Directional delay-period activity encoding the location of the visual cue and directional presaccadic activity encoding the location of the visual cue. A: neuron activity during the ODR task. This neuron exhibited significant delay-period activity when visual cues were presented at the 225° (z = 3.47, P < 0.001), 270° (z = 3.76, P < 0.001) and 315° (z = 3.65, P < 0.001) locations and significant presaccadic activity when visual cues were presented at the 0° (z = 3.56, P < 0.001), 45° (z = 3.30, P < 0.001), 225° (z = 4.65, P < 0.001), and 270° (z = 5.19, P < 0.001) locations. The max cue conditions were 270° for delay-period activity and 270° for presaccadic activity. B: neuron activity during the R-ODR task. Significant delay-period activity was observed when visual cues were presented at 90° (z = 2.75, P < 0.01) and 270° (z = 4.82, P < 0.001) locations and significant presaccadic activity was observed when visual cues were presented at the 270° (z = 5.41, P < 0.001) location. The max cue conditions were 270° for delay-period activity and 270° for presaccadic activity. All cue eccentricities were 17°. The histogram binwidth was 30 ms. The numbers at the top left of each figure indicate the location of the visual cue (left) and the direction of the saccade (right).

Figure 13A shows distributions of the difference between the best directions in the two tasks (D_R-ODR-D_ODR) for all directional response-period activity. In 35% of the neurons (20/57), the differences between the best directions in the two tasks were distributed between 45° and 45°. For these neurons, the mean difference between the best directions in the two tasks was 12.4 ± 26.5° in presaccadic activity (n = 5) and 3.84 ± 34.9° in postsaccadic activity (n = 15).

Sixty-five percent of the neurons (13/20) whose response-period activity encoded the location of the visual cue also had cue-period activity and/or delay-period activity in both tasks. Among these, 11 neurons (85%) exhibited both directional delay-period activity and directional response-period activity in both tasks. An example of these neurons is shown in Fig. 14. In the ODR task, this neuron exhibited significant delay-period activity when the visual cues were presented at the 225°, 270°, and 315° locations (Fig. 14A). The max cue condition of delay-period activity was 270° in the ODR task. In the R-ODR task, significant delay-period activity was also observed when the visual cues were presented at the 90° and 270° locations (Fig. 14B). The max cue condition of delay-period activity was 270° in the R-ODR task. The max cue conditions of delay-period activity were the same in the two tasks. Therefore this neuron's directional delay-period activity is considered to encode the location of the visual cue. As shown previously, this neuron also exhibited directional presaccadic activity in both tasks. The max cue condition for presaccadic activity was 270° in both tasks. These results indicate that the max cue conditions were the same for both delay-period activity and presaccadic activity in both tasks and therefore that both activities encode the location of the visual cue.

Figure 15 shows other examples of the neuron with both delay-period and presaccadic activities (n110) and the neuron with both delay-period and postsaccadic activities (n123). In these examples, the max cue conditions for delay-period and response-period activities were the same (270°) in both tasks, regardless of the directions of the saccades. Therefore both delay-period and response-period activities are thought to encode the location of the visual cue. Of 11 neurons with both delay-period and response-period activities, 10 showed identical max cue conditions for both delay-period and response-period activities, and both activities encoded the location of the visual cue. Among these 10 neurons, 5 exhibited postsaccadic activity and 5 exhibited presaccadic activity.

View larger version (26K): [in this window] [in a new window]   Fig. 15. Comparison of tuning curves of delay-period activity and response-period activity in the ODR and R-ODR tasks for the same neuron. A: an example of a neuron in which the best directions of both delay-period activity and presaccadic activity were almost identical in the 2 tasks. Left: delay-period activity. The best directions were 247.58° in the ODR task (, R2 = 0.927) and 286.62° in the R-ODR task (- - -, R2 = 0.999). Right: presaccadic activity. The best directions were 251.04° in the ODR task (, R2 = 0.800) and 272.92° in the R-ODR task (- - -, R2 = 0.999). B: another example of a neuron in which the best directions of both delay-period activity and postsaccadic activity were almost identical in the 2 tasks. Left: delay-period activity. The best directions were 283.85° in the ODR task (, R2 = 0.700) and 283.25° in the R-ODR task (- - -, R2 = 0.991). Right: postsaccadic activity. The best directions were 266.93° in the ODR task (, R2 = 0.964) and 266.86° in the R-ODR task (- - -, R2 = 0.993).

Comparison of peak activity in the ODR and R-ODR tasks

To examine whether or not the magnitude of pre- or postsaccadic activity is task-dependent, we compared the peak discharge rates of pre- or postsaccadic activity in the two tasks for 27 neurons that exhibited good Gaussian fitting. Figure 13B is a scattergram of peak discharge rates of pre- or postsaccadic activity in both tasks. The mean peak discharge rate of presaccadic activity was 27.91 ± 7.09 spikes/s (n = 6) in the ODR task and 31.22 ± 12.91 spikes/s (n = 6) in the R-ODR task. The mean peak discharge rate of postsaccadic activity was 22.98 ± 6.95 spikes/s (n = 21) in the ODR task and 23.29 ± 8.94 spikes/s (n = 21) in the R-ODR task. There was no significant difference between the peak discharge rates in the two task conditions with regard to either presaccadic activity (Wilcoxon signed-rank test, P = 0.60) or postsaccadic activity (Wilcoxon signed-rank test, P = 0.99).

Population analysis of delay-period activity encoding the location of the visual cue and the direction of the saccade

We examined what type of information each task-related activity encoded during spatial working memory processes. As a result, we found that directional cue-period activity encoded the location of the visual cue. For directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. For directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. In addition, as is seen in Figs. 7A, 10A, and 13A, the means of the difference between the best directions (D_R-ODR-D_ODR) in two tasks was 7.9° in cue-period activity, 18.9° in delay-period activity, and 67.1° in response-period activity. The mean of these distributions was shifted progressively farther to 90°. These results suggest that the transformation of information from visual input to motor output occurs during the delay period in the prefrontal cortex.

To elucidate the process of information transformation from visual input to motor output, we made population histograms (population average of delay-period activity) using neuronal activities at the max cue conditions for all neurons with delay-period activity that encoded the location of the visual cue and the direction of the saccade, respectively. Using directional delay-period activity that encoded the location of the visual cue (n = 48), we made two population histograms; one histogram (ODRcue) using activities at the max cue condition in the ODR task and another (R-ODRcue) using activities at the max cue condition in the R-ODR task. Similarly, using directional delay-period activity that encoded the direction of the saccade (n = 7), we made two other population histograms; one histogram (ODRsac) using activities at the max cue condition in the ODR task and another (R-ODRsac) using activities at the max cue condition in the R-ODR task.

As shown in Fig. 16A, ODRcue exhibited tonic excitation during the delay period. Throughout the delay period, the discharge rate of delay-period activity was maintained at around 14 spikes/s. Similarly, R-ODRcue also exhibited tonic excitation during the delay period (Fig. 16B), although the discharge rate of delay-period activity increased slightly from the beginning of the delay period (13 spikes/s) to the end of the delay period (15 spikes/s). These results indicate that delay-period activity encoding the location of the visual cue shows tonic excitation during the 3-s delay period and that the discharge rate of delay-period activity maintains at a similar rate throughout the delay period in both tasks. Among 48 neurons with directional delay-period activity that encoded the location of the visual cue, 31 exhibited tonic excitation, 8 exhibited gradual increase of activity, 3 exhibited gradual decrease of activity, and 6 showed tonic inhibition during the delay period.

View larger version (31K): [in this window] [in a new window]   Fig. 16. Comparison of 2 types of population histograms (population average of delay-period activity) for each task. A: comparison of the population histogram encoding the location of the visual cue (ODRcue, blue line) and the population histogram encoding the direction of the saccade (ODRsac, red line) in the ODR task. B: comparison of the population histogram encoding the location of the visual cue (R-ODRcue, blue line) and the population histogram encoding the direction of the saccade (R-ODRsac, red line) in the R-ODR task. C, cue period; D, delay period; R, response period.

On the other hand, ODRsac shows a gradual increase of activity during the delay period, and reached 18 spikes/s at the end of the delay period (Fig. 16A). Similarly, R-ODRsac shows more rapid increase of activity after the onset of the delay period until the end of the delay period and reached 20 spikes/s at the end of the delay period (Fig. 16B). Among seven neurons with directional delay-period activity that encoded the direction of saccade, three exhibited tonic excitation and four exhibited gradual increase of activity during the delay period.

Comparing the temporal patterns of activation between ODRcue and ODRsac (Fig. 16A), during the early phase of the delay period, the discharge rates of ODRcue and ODRsac were almost the same. However, the discharge rate of ODRsac became higher than ODRcue during the late phase of the delay period. Similarly, comparing the temporal patterns of activation between R-ODRcue and R-ODRsac (Fig. 16B), the discharge rates of R-ODRcue and R-ODRsac were almost the same at the early phase of the delay period. However, the discharge rate of R-ODRsac increased rapidly during the late phase of the delay period. These results indicate that, at the population level, neuronal activity encoding motor outputs gradually develops during the delay period, whereas neuronal activity encoding visual inputs maintains at a constant level during the delay period, suggesting that the transformation of information from visual input to saccade output occurs during the delay period.

	DISCUSSION

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