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Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Submitted 22 October 2003; accepted in final form 10 May 2004
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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50 µA and then examined suppressive effects of stimulation at the same site on Vsacs and Msacs. FEF stimulation suppressed the initiation of both Vsacs and Msacs during and about 50 ms after stimulation at stimulus intensities lower than those for eliciting Esacs, but did not affect the vector of these saccades. Suppression occurred for ipsiversive but not contraversive saccades, and more strongly for saccades with larger amplitudes and those with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for suppression was about 50 ms before saccade onset, which suggests that suppression occurred in the efferent pathway for generating Vsacs at the premotor rather than the motoneuronal level, most probably in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of ipsilateral saccades were distributed over the classical FEF where saccade-related movement neurons were observed. The results suggest that the FEF may play roles in not only generating contraversive saccades but also maintaining visual fixation by suppressing ipsiversive saccades. |
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Welch and Stuteville 1958). Electrical stimulation of the FEF evokes saccades with short latencies at low thresholds (Bruce et al. 1985; Robinson and Fuchs 1969), and the FEF contains neurons that respond to visual stimuli and neurons that discharge before saccades (Bruce and Goldberg 1985). When an interesting object appears in a visual field, a saccade occurs to that object of interest, and then visual fixation is required to hold the image of the target on the fovea. The FEF has neuronal activity related to visual fixation (Bizzi 1968; Bruce and Goldberg 1985; Suzuki and Azuma 1977). During fixation, potential saccades to other objects in the visual field must be suppressed. Therefore saccades should be suppressed with visual fixation and this suppression should be released when the line of sight changes. Although the FEF is implicated in saccade generation, there is some evidence that the FEF also exerts suppressive control on saccades. Human patients with unilateral frontal lobe lesions have difficulty in suppressing reflexive saccades to inappropriate targets in the peripheral visual field (Braun et al. 1992; Guitton et al. 1985). Lesion studies in the monkey showed that FEF inactivation increased the frequency of premature saccades to ipsilateral targets (Dias and Segraves 1999; Sommer and Tehovnik 1997). These findings may be interpreted as the impairment of suppressive function of the FEF in normal oculomotor behavior. In fact, stimulation of the FEF suppressed saccade generation (Azuma et al. 1986; Burman and Bruce 1997). Suppression produced by FEF stimulation was first reported for visually guided saccades (Vsacs) (Azuma et al. 1986). Later, however, Burman and Bruce (1997) showed that FEF stimulation mainly suppressed memory-guided saccades (Msacs) to the contralateral side. Since this latter report, the effects of FEF stimulation on the suppression of saccades have not been systematically analyzed, and the above discrepancies have not yet been resolved.
The present study was performed to investigate the properties of the suppressive effects of electrical stimulation of the FEF on saccades in trained monkeys. The results showed that FEF stimulation strongly suppressed the initiation of both Vsacs and Msacs. We found 2 types of suppression for saccades produced by stimulation of the FEF and its vicinity: suppression of ipsilateral saccades and suppression of bilateral saccades. This report describes the characteristic features of the unilateral suppression of ipsiversive Vsacs and Msacs caused by electrical stimulation of a wide area in the FEF where electrical stimulation evoked saccades (Esacs) at 50 µA, and a companion article reports that stimulation of a localized area in the FEF suppresses saccades in all directions (Izawa et al. 2004).
These results were briefly reported previously (Izawa et al. 2001).
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Behavioral training
During training and experimental sessions, the monkey was seated in a primate chair facing a tangent translucent screen 1.5 x 1.5-m square and 57 cm in front of it. Ambient room light was dim. Each monkey was first trained to fixate a tiny light spot (0.4° in visual angle, 2 cd/m2) that was back-projected at the center of the screen using a pair of mirrors attached to galvanometers (Suzuki and Azuma 1977; Wurtz 1969). The screen was evenly illuminated at 1 cd/m2 to eliminate stray light around the spot. The monkey was trained to press a bar with its hand on the appearance of the center spot, which occurred after an intertrial interval of 5 s. While the bar was held down, the spot remained illuminated for a variable duration of 1–4 s, and then was slightly brightened (0.3 log unit) for 0.5 s. When the monkey released the bar only during this short brightening period, it received 0.2 ml of juice as a reward. Otherwise, the trial was terminated without a reward, and a new trial began. Fixation behavior was elicited because the monkey had to look at the spot to notice its brightening for rapid bar release.
When the training of the fixation task was completed, the monkey was required to make Vsacs. For this task, the center spot was turned off, and another light spot was simultaneously turned on elsewhere on the screen as a visual target. The monkey learned to make a saccade to the target because it had to observe its brightening. When the monkey released the bar during brightening of the target light, it received a reward. The monkey was also trained to make Msacs. In this task, the monkey first fixed its eyes on the center spot. During this fixation, another instruction target spot was flashed at a location on the screen for 0.5 s. This time, the monkey was required to maintain its line of sight on the center spot, while the center spot remained on. At 0.5–1.5 s after the flashed target, the center spot was turned off as a cue to make a saccade. The monkey had to make a saccade to the previously instructed location within an error window of ±3° around the visual target. Otherwise, the trial was terminated without a reward, and a new trial began. At 0.6–1.5 s after the disappearance of the center spot, the target spot that had been flashed previously was turned on again for 0.5 s to confirm a correct Msac. When the monkey released the bar only during this short brightening period, it received a reward.
Surgery
After the behavioral training, a head holder and a cylinder for a micromanipulator were implanted in the skull. The monkey was anesthetized with an intramuscular injection of ketamine hydrochloride (Ketalar, 10 mg /kg; Sankyo, Tokyo, Japan), followed by an intravenous injection of pentobarbital sodium (Nembutal, 10 mg/kg; Abbott AG, Baar/Zug, Switzerland). The latter was supplemented for maintenance, when required. Under aseptic conditions, 3 bolts for head stabilization and a 25-mm-diameter cylinder were attached to the skull over the left periarcuate cortex centered at A25, L18 for monkey Sui and at A30, L20 for monkey Bell. These implants were made of Ni–Co–Mo alloy (22A; Nippon Kinzoku, Tokyo, Japan) to minimize tissue reactions (Suzuki and Azuma 1983). After surgery, the monkey was given antibiotics (Cefamezin, 50 mg/kg per day; Fujisawa, Osaka, Japan) for 1 wk.
Microstimulation and experimental procedures
We used glass-insulated elgiloy microelectrodes (Suzuki and Azuma 1976) with impedances of 0.3–0.5 M
at 1 kHz in Ringer solution. The electrode was introduced into the FEF with a micromanipulator (MO-95; Narishige, Tokyo, Japan) attached to the implanted cylinder. While recording neuronal activity at 200- or 400-µm intervals within the cortex, we switched from a recording circuit to a stimulation circuit to apply microstimulation using the same electrode. Constant-current stimulation trains were generated using a Nihon Kohden ss-1945 stimulator. Trains generally consisted of 40–60 monopolar cathodal pulses of 1-ms duration at 5-ms intervals, and 80 µA. During data collection, the monkey first performed a fixation task. In stimulation trials, microstimulation was first applied to the FEF during fixation on the center spot and the threshold for evoking eye movements was determined. In subsequent stimulation trials, the monkey was instructed to make either Vsacs or Msacs, and the offset of the center fixation spot was usually accompanied by the onset of a train of stimulation pulses. Current intensities were varied systematically to determine the suppressive effects of stimulation on saccades. The effect of stimulation for eliciting Esacs during fixation was often confirmed after the suppressive effect was examined. Virtually all sites in the following descriptions were judged as being in the gray matter, based on the background neuronal activity recorded before stimulation (see Fig. 3). In each track, the effect of stimulation was systematically examined throughout the gray matter and the white matter beneath the FEF. Several representative stimulation sites were marked with iron deposits by passing currents (electrode positive, 400 µC) through the elgiloy microelectrode (Suzuki and Azuma 1987). Because both monkeys are being used for further experiments, we are unable to provide histological verification of recording sites.
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The behavioral tasks, presentation of light spots, and data acquisition were controlled by IBM-compatible computers. Eye movements were recorded by a camera measurement system, using the corneal reflection image of infrared light (Azuma et al. 1996), with which we could measure vertical and horizontal eye positions with an accuracy of 0.3° and at a sampling rate of 4 ms. Eye position signals were calibrated by having the monkey fixate targets at known eccentricities (10, 20, and 30°) on the horizontal and vertical meridians and diagonal axes. Horizontal and vertical component signals of eye movements and neuronal activity, with respect to behavioral event indicators, were stored on computer hard disks and displayed on an oscilloscope. Eye movements and neuronal activity were sampled every 4 and 1 ms, respectively. The onset of each saccade was identified in the eye-position traces by a mouse-controlled cursor. Subsequent off-line data analyses were performed using Matlab (The MathWorks, Natick, MA) programs. A preferred direction for suppression was given by a value in the fitted Gaussian function. Statistical analysis was performed with a Mann–Whitney U test for single comparisons. A Kruskal–Wallis ANOVA or a Friedman ANOVA with replication followed by a multiple comparison test (Steel method) was performed for multiple comparisons. Correlations between data sets were assessed by measuring the Pearson correlation coefficient.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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The FEF is classically defined as an area in the frontal cortex where electrical stimulation produces eye movements (Wurtz and Mohler 1976). In the monkey, such an area is located along the arcuate sulcus at the level of the principal sulcus (Robinson and Fuchs 1969). We could identify the location of both sulci under the dura, when we implanted the cylinder (Fig. 1Aa ). Based on these anatomical landmarks, we inserted an electrode into the prearcuate area, which previous studies had considered to be the FEF (Wurtz and Mohler 1976), and confirmed that electrical stimulation of this area elicited eye movements at a low stimulus intensity (50 µA; classical FEF) (Fig. 1Ab). Figure 1B shows an example of eye movements produced by stimulation of the frontal cortex at site 1 in Fig. 1Ab. Stimulation was applied while a monkey fixed its eyes on a central fixation target in the fixation task (central fixation period). Stimulation of the FEF at 20 µA evoked no eye movement, but stimulation of the same site at 25 µA evoked saccadic eye movements with a horizontal component contraversive to the stimulated side [electrically evoked saccades (Esacs)]. These Esacs evoked by stimulation during the central fixation period were always followed by return saccades (Goldberg et al. 1986). Because Esacs were evoked in about 50% of the trials at 25 µA in this example, we regarded this stimulus intensity as the site's threshold for evoking Esacs. At threshold, the latencies and amplitudes of these Esacs usually fluctuated, but became fixed at suprathreshold stimulus intensities. With an increase in the stimulus intensity, the latency of Esacs was slightly shortened and the amplitude of Esacs was slightly increased, whereas there was no change in the direction of Esacs. Stimulation at 50 µA constantly evoked 24.2° Esacs at an angle of 0.5° (0° is horizontal right, and the value of the angle increases counterclockwise) and with a latency of 59 ms. Thus when saccades were elicited by stimulation of 50 µA, we identified a stimulation site as being within the classical low-threshold FEF (Bruce et al. 1985).
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STIMULUS PARAMETERS FOR EFFECTIVE SUPPRESSION OF VSACS. To find the most effective stimulus parameters for suppression of saccades, we systematically examined the effects of varying stimulus parameters on the suppression of Vsacs. Figure 1D shows an example of the effect of varying the train duration on Vsac suppression. The train duration was increased by changing the number of pulses in a stimulus train, while the stimulus intensity and interval were kept constant. In this example, the stimulus intensity of 24 µA for 200 ms, which was well below the threshold for evoking Esacs (50 µA), was strong enough to suppress the initiation of Vsacs. A train of 10 and 20 stimulus pulses slightly delayed the onset of Vsacs and a train of 30 or more stimulus pulses clearly delayed the onset of Vsacs. Vsacs were completely suppressed during stimulation for up to 1 s (200 pulses), and suppression continued for about 50–70 ms after the end of stimulation. As in this case, stimulation at a sufficiently suprathreshold intensity generally caused the suppression of Vsacs during stimulation and for up to about 50 ms after stimulation offset. However, suppression did not always continue during stimulation, but rather depended on the stimulation site and intensity, so that Vsacs with delayed onsets in some trials occurred during prolonged stimulation (500 or 700 ms). We examined the effect of the stimulus pulse interval on the suppression of Vsacs (not shown). Pulse intervals were varied from 3.3 to 9 ms, whereas the stimulus intensity and train length were kept constant. The suppression of Vsacs was weak using a stimulus train with a 3.3-ms interval, but stable using a stimulus train with a 5-ms interval. For intervals of 6–9 ms, the suppressive effect was the same as for the 5-ms interval, or tended to fluctuate between trials with sufficient and weak suppression. Thereafter, the pulse interval was fixed at 5 ms in later experiments.
To examine the effects of varying the stimulus intensity on the suppression of ipsiversive and contraversive Vsacs, stimulus intensities were increased from 0 to 50 µA at a 5-µA interval (Fig. 2). Although no effect appeared at 20 µA, a delay in the initiation of ipsiversive 20° Vsacs occurred and the fluctuation of the latencies of individual Vsacs increased at 25 µA (Fig. 2, left column). When the stimulus intensity was increased to 45 µA, the complete suppression of Vsacs occurred during stimulation and this suppression persisted for about 50 ms after stimulation offset. With a further increase to 50 µA, the suppression became stronger, although Esacs were evoked in some trials. The threshold for suppression was defined as the least stimulus current required to produce an increase in the saccade latency that was more than 2 SDs of the control saccade latency. The mean ± SD of the latency of control Vsacs was 181 ± 24 ms in monkey Sui (n = 261), and 188 ± 19 ms in monkey Bell (n = 245). Based on this criterion, we determined that the threshold for suppression was 25 µA in the example in Fig. 2. At the same stimulation site, contraversive Vsacs were not suppressed even at 50 µA, but the latencies of contraversive 20° Vsacs at 35 µA (median 137 ms) or more tended to be shorter than in control (median 164 ms) (U test, P < 0.01 at 
35 µA). In spite of the effects of stimulation on Vsac initiation, there was no significant difference in the amplitude or direction of ipsiversive Vsacs (U test, P = 0.33 and P = 0.79, respectively) and contraversive Vsacs (U test, P = 0.17 and P = 0.51, respectively) in control and stimulation trials (45 µA), suggesting that the accuracy of Vsacs was maintained. The amplitude and direction of contraversive Vsacs were sometimes affected, when stimulation current was increased very close to threshold for Esacs. However, they were not usually affected, given that the thresholds for suppressing Vsacs were well below the threshold for evoking Esacs at most stimulation sites. Therefore such interaction will not be described in detail here, but the interaction between Vsacs and Esacs will be reported in a companion paper (Izawa et al. 2004).
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). Because saccade-related movement neurons like this neuron were found in tracks including the suppression sites, it was concluded that the suppression sites were located in the classical FEF.
The delay in the initiation of ipsiversive Vsacs caused by FEF stimulation depended on the stimulus intensity and the stimulation site. At some stimulation sites, a suppressive effect was observed at <10 µA, even though Esac thresholds were >50 µA, and the difference between the thresholds for Esac generation and Vsac suppression was more than 40 µA. At some other FEF sites, stimulation evoked Esacs, but stimulation of the same sites at an intensity just below the Esac threshold had no suppressive effect on Vsacs. The suppression of ipsiversive Vsacs was found in 293 of 302 tracks in which electrical stimulation evoked contraversive Esacs at 50 µA, indicating that suppression sites were prevalent in the classical FEF.
SUPPRESSIVE EFFECTS OF FEF STIMULATION ON VSACS WITH DIFFERENT DIRECTIONS. To determine the effective direction of suppression, we examined the suppressive effects of FEF stimulation on Vsacs by changing their directions to 8 or 10 different directions with the amplitude of Vsacs (10°) fixed (Fig. 4). The latencies of Vsacs were significantly longer in stimulation trials than in control trials (Friedman ANOVA, P < 0.0001). Suppression occurred predominantly for Vsacs with an ipsilateral horizontal component (U test, P < 0.05 for 135, 157.5, 180, 202.5, and 225°) (Fig. 4A, a–e), and only slightly for vertical Vsacs with a downward (U test, P < 0.05) (Fig. 4Af) or upward direction (Fig. 4Aj). In contrast, suppression was not observed for Vsacs with a contralateral horizontal component (U test, P > 0.05 for 315, 0, and 45°) (Fig. 4B, g–i), but their latencies tended to be rather shortened by 5–30 ms. The correlation between the latencies of horizontal and vertical components of individual oblique Vsacs was highly significant (y = 0.99x + 2.72, r = 0.99, P < 0.001, n = 23), and the slope (0.99) and intercept (2.72) of a regression line was not significantly different from 1 and 0 (t-test, P = 0.85 and P = 0.66), respectively. Therefore both the horizontal and vertical components of individual Vsacs were always synchronously suppressed by stimulation. The preferred direction for the suppression of Vsacs was determined by using the difference in latency between Vsacs in stimulation and control trials (dotted line in Fig. 4B) as an index of the strength of the suppression in each direction because the latencies of Vsacs in different directions were varied in the control. In the example in Fig. 4, suppression showed a preference for the ipsilateral downward direction (198.4°). To examine the relationship between the directions of Esacs and suppression, we increased the stimulus intensity at the same stimulation site to evoke contraversive Esacs. Esacs were evoked at a threshold of 50 µA to the contralateral downward direction (340.1°) (Fig. 4B, arrow). We compared the preferred direction of suppression and the Esac direction at all 14 stimulation sites where similar analysis was performed. The preferred direction of suppression was nearly opposite the direction of Esacs at 8 stimulation sites, whereas at the other 6 sites the vertical components were in the same direction and the horizontal components were opposite.
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SUPPRESSIVE EFFECTS OF FEF STIMULATION ON VSACS WITH DIFFERENT AMPLITUDES.
To investigate the suppressive effects of FEF stimulation on Vsacs with different amplitudes, the Vsac amplitude was changed from 5 to 20° at intervals of 5° (Fig. 5). Under the control condition with no stimulus, the latencies of Vsacs tended to decrease as their amplitudes increased (Fig. 5A, left column). This inverse relationship between the latency and amplitude of Vsacs is consistent with a previous observation that the shorter the latency, the greater the amplitude of saccades evoked by stimulation of the superior colliculus (SC) (Stanford et al. 1996). When the stimuli were applied, the latencies of ipsiversive Vsacs increased (Friedman ANOVA, P < 0.0001; Steel method, P < 0.05 for 10 µA), but those of contraversive Vsacs did not (Friedman ANOVA, P = 0.10). FEF stimulation at 20 µA suppressed ipsiversive Vsacs with amplitudes of 15 and 20°, whereas the same stimulation did not suppress contraversive Vsacs of any amplitude (Fig. 5A, middle column). At 30 µA, all ipsiversive Vsacs with amplitudes of 5–20° were suppressed, and suppression was greater in Vsacs with larger amplitudes (Fig. 5A, right column). At 40 µA, stimulation strongly suppressed ipsiversive Vsacs of all amplitudes and suppression continued for about 50 ms after the end of stimulation, but contraversive Vsacs were not suppressed at all by the same stimulation. The strength of the ipsilateral suppression depended on the saccade amplitude, and was saturated at a stronger stimulus intensity at all of the 13 stimulation sites tested. As shown in Fig. 5B, ipsiversive Vsacs with larger amplitudes were suppressed at lower thresholds by FEF stimulation, whereas a similar trend was not seen for contraversive Vsacs of any amplitude. Even when the preferred direction of suppression was almost opposite the Esac direction, the suppression was stronger for larger Vsacs irrespective of the amplitudes of Esacs.
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20 µA). Stimulation of the left FEF at 30 µA caused a delay in the initiation of ipsiversive Vsacs with an initial eye position of right 20°, and this delay increased when the initial eye position was shifted from right 20° to left 20° (Fig. 6A). At 40 µA, the delay for Vsacs with contralateral initial eye positions was greater, whereas at 20 µA, the delay with ipsilateral initial eye position was smaller than that at 30 µA (Fig. 6C). These results showed that the more the initial eye position was shifted toward the direction of ipsiversive Vsacs from the center position, the stronger the suppression of the Vsacs (Fig. 6, A and C). In contrast, the same stimulation did not delay the onset of contraversive Vsacs with any initial eye position, but rather shortened the latency of contraversive Vsacs with any contralateral initial eye position (Friedman ANOVA, P < 0.001) (Fig. 6, B and D). A similar tendency was observed at all of the 6 stimulation sites examined.
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130 ms completely suppressed Vsacs during stimulation in all trials. Nonsuppressed Vsacs at 140–160 ms tended to occur earlier than Vsacs in the control. Because the latencies of Vsacs fluctuated even in the control, suppressed Vsacs at these intervals were most likely Vsacs that should have occurred at longer onset latencies. Nonsuppressed Vsacs generated at shorter latencies had almost the same amplitudes as in the control, but those with average latencies had slightly depressed amplitudes. Figure 7B shows the time course of Vsac latencies in Fig. 7A (thick line) and in the control without stimulation (thin line). Suppression of Vsacs started at an interval of 150 ms, and the delay of Vsacs became maximal at an interval of 130 ms. The Vsac latency decreased with regard to the stimulation onset as the interval was further decreased. The systematic effects of varying the stimulus intensity on the time course of suppression at the same stimulation site are illustrated in Fig. 7C. The time courses of suppression for 30 and 40 µA were very similar and peak suppression occurred at 130 ms. The time course for 20 µA had a peak at 130 ms, but the Vsac latencies returned to almost the control level at 110 ms. At 10 µA, a weak suppressive effect was observed only at 150–130 ms. These results showed that the latest timing of stimulus train onset for effective suppression was about 130 ms after visual target onset, which corresponded to about 50 ms before Vsac onset. Similar results were obtained at all of the 17 stimulation sites tested. Stimulation before this timing suppressed Vsacs in all trials, whereas stimulation after this timing did not suppress Vsacs, except when Vsacs that should have occurred at a longer onset latency were occasionally suppressed.
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130 ms, Vsacs were almost completely suppressed in more than half of the trials during stimulation. In the second method, the onset of a stimulus train with a fixed stimulus intensity (47 µA) was adjusted to coincide with the visual target onset, and the number of stimuli at a 5-ms interval was increased (Fig. 7E, inset). An increase in the number of stimuli gradually delayed the onset of Vsacs. To determine the earliest effective stimulus for suppression, the latencies of Vsacs were plotted relative to the stimulus train duration (Fig. 7E). The delay in Vsac onset at a train duration of 125 ms (26 pulses) or more was statistically significant (Kruskal–Wallis ANOVA, P < 0.0001; Steel method, P < 0.05). Therefore the earliest onset of the suppression of ipsiversive Vsacs (
55 ms before Vsac onset) was slightly earlier than the latest onset of a stimulus train (50 ms before Vsac onset). Suppressive effects of FEF stimulation on Msacs
So far, we have described the suppressive effects of FEF stimulation on Vsacs. In this section, we describe the properties of the suppression of Msacs caused by FEF stimulation and compare the suppression on Vsacs with the suppression on Msacs. We first identified suppression sites in the FEF for ipsiversive Vsacs, as described above, and then examined the effects of stimulation at the same sites on Msacs. In the example in Fig. 8A, the onset of ipsiversive Vsacs was delayed at a threshold of 15 µA, and Esacs were evoked at 40 µA in some trials. Stimulation of the same FEF site at the same stimulus parameters also suppressed ipsiversive Msacs, but not contraversive Msacs (Fig. 8B). The suppression threshold for ipsiversive Msacs was 15 µA, which was the same as that for ipsiversive Vsacs. Thresholds for the suppression of Vsacs and Msacs were very similar at 6 stimulation sites, but were slightly different at 4 stimulation sites (lower for Vsacs, 3 sites; lower for Msacs, 1 site). However, the correlation between them was significant (y = 0.99x + 7.31, r = 0.80, P < 0.01, n = 10). In addition, the depth-threshold curves for the suppression of Msacs and Vsacs were usually similar along individual penetration tracks (not shown).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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). Later, however, Burman and Bruce (1997) reported that Vsacs were less severely suppressed than Msacs and contraversive saccades were usually more strongly suppressed than ipsiversive saccades. In their study, low-intensity stimulation (20–50 µA, 350- to 450-ms trains) suppressed at least one of the 3 task-related saccades (Vsac, Msac, and antisaccade) at 18 of 54 sites where electrical stimulation did not elicit Esacs or any other eye movement. At these "pure suppression" sites, Msacs were most dramatically suppressed and often hypometric, and contraversive saccades were usually more strongly suppressed than ipsiversive ones. At their "pure suppression" sites, cells with foveal or postsaccadic responses were most prevalent. Burman and Bruce (1997) also reported that at many FEF sites (their saccade sites) at which low-threshold Esacs could be elicited (12 of 23 sites tested), stimulation produced suppressive effects similar to those for "pure suppression" sites. There are several differences between our study and that of Burman and Bruce (1997). The present suppression sites are different from their "pure suppression" sites in that 1) Esacs could be evoked at 50 µA, 2) both Msacs and Vsacs were equally suppressed, 3) only ipsiversive Msacs and Vsacs were suppressed, 4) locations of such suppression sites were widely distributed over a classical FEF, and 5) saccade-related movement neurons were prevalent. In contrast, the present suppression is more likely to be similar to their suppression at saccade sites in that the suppression occurs at the sites where Esacs were evoked at 50 µA.
However, there are several reasons why the present suppression differs from that reported by Burman and Bruce (1997). The most important reasons may be related to kinds of suppressed saccades and threshold and directionality of suppression: we found that our suppression occurred equally on both Vsacs and Msacs at stimulus intensities well below the threshold for eliciting Esacs at each site and only ipsiversive saccades were suppressed. Burman and Bruce (1997) reported that at 4 of 5 saccade sites tested with subthreshold currents for eliciting Esacs, suppression occurred on saccades in all directions but the direction of the Esac in which direction saccades were facilitated, and the accuracy of suppressed saccades was often altered. Therefore they concluded that task-related saccades whose vectors differed from the vector of Esac elicited at a stimulation site were suppressed by stimulation of the same site. Although we found that contraversive saccades were facilitated at some stimulation sites (Figs. 4 and 9), suppression occurred only on ipsiversive saccades even at such sites.
As to the relation between the Esac amplitude and the amplitudes of suppressed saccades, we found that initiation of the larger Msacs and Vsacs was more strongly suppressed irrespective of the amplitude of the Esac elicited at the same stimulation site. Furthermore, the accuracy of Vsacs and Msacs was not usually affected at our suppression sites. At their (Burman and Bruce 1997) saccade sites some suppression was observed at stimulus intensities subthreshold for eliciting Esacs, but they also reported that similar suppression effects of stimulation were observed in trials when Esacs were elicited. In these trials, the interaction between Esacs and Vsacs or Msacs has to be taken into consideration. This problem will be dealt with in an accompanying paper (Izawa et al. 2004) with respect to the suppression of contraversive saccades. Some methodological differences may account for the differences obtained in the present and Burman and Bruce (1997) experiments. Our experiments usually involved the delivery of 40–60 monopolar cathodal pulses of 1-ms duration at 5-ms intervals. On the other hand, in the Burman and Bruce (1997) experiments, biphasic pulses with each pulse pair 0.4 ms in duration were used and train duration was 350–450 ms, although the frequency used seemed not to be described. The latencies of saccades of the monkeys used in the 2 experiments also differed significantly. In the Burman and Bruce (1997) paper, latencies of Vsacs are 274–344 ms but are about 180 ms in our experiments. The stimulation site in the FEF may also contribute to the difference in the laterality of suppression. Most of the present stimulation sites for suppression were distributed widely over the classical FEF area where electrical stimulation elicited Esacs at low intensities, whereas Burman and Bruce (1997) reported that their stimulation sites for suppression were located near the spur of the arcuate sulcus, similar to the smooth pursuit subregion of the FEF (MacAvoy et al. 1991; Tanaka and Fukushima 1998).
The duration and intensity of FEF stimulation influenced the duration of the suppression, but did not influence the accuracy of Vsacs. The signals that convey information about the metrics of a saccade can be dissociated from the saccadic trigger signal (Fuchs et al. 1985; Sparks et al. 1987). Therefore the present result suggests that FEF stimulation may have a suppressive effect on the saccade trigger system rather than the metric controlling system. The preferred direction for the suppression of ipsiversive Vsacs was almost 180° opposite the direction of Esacs at 8 of 14 stimulation sites, but was different from directly opposite the Esac direction at 6 of 14 sites. This latter finding supports the interpretation that unilateral suppression of Vsacs is not ascribed to reciprocal inhibition that occurs at a motoneuronal level by inhibitory burst neurons (IBNs) activated by FEF stimulation. The pathway responsible for FEF-associated suppression must either inhibit premotor neurons that control oblique saccades or simultaneously inhibit horizontal and vertical premotor neurons (Büttner-Ennever and Büttner 1988; Fuchs et al. 1985) because FEF stimulation synchronously suppressed the onsets of the horizontal and vertical components of ipsiversive saccades. Stimulation of the FEF increased the latencies of ipsiversive Vsacs at intensities lower than those that evoked Esacs at each stimulation site, but decreased the latencies of contraversive Vsacs. This finding suggests that FEF stimulation may facilitate the activity of neurons in the pathway for generating contraversive Vsacs, and reciprocally suppress the activity of neurons in the pathway for generating ipsiversive Vsacs. Abducens motoneurons receive excitation by excitatory burst neurons (EBNs) from the contralateral SC and inhibition by IBNs from the ipsilateral SC (Grantyn and Grantyn 1976, 1982; Izawa et al. 1999; Precht et al. 1974). Therefore the FEF suppression of ipsiversive Vsacs may be attributable to activation of this reciprocal inhibition by the SC. Reciprocal inhibition at the level of ocular motoneurons should result in a reduction of Vsac amplitude as well as a delay of Vsac initiation, but the present FEF stimulation did not influence the amplitude of Vsacs. In addition, the present results showed the stronger suppression of larger ipsiversive Vsacs. Larger ipsiversive Vsacs are not more easily suppressed at the motoneuronal level by reciprocal inhibition by IBNs that might be activated by FEF stimulation, given that ipsilateral abducens motoneurons receive stronger excitation by the SC from the contralateral FEF for the larger Vsacs. Furthermore, we found that Vsacs with initial eye positions shifted more in the saccadic direction were more strongly suppressed. By shifting the initial eye position in the direction of Vsac from the center, the motoneuronal membrane potential is depolarized, so that a decrease in the rising slope of excitatory input may result in delaying spike initiation (Eccles 1964). If FEF stimulation had activated contralateral IBNs by the SC and caused hyperpolarization in ipsilateral abducens motoneurons, this change in membrane potential should have decreased the latency of ipsiversive Vsacs (Izawa et al. 1999). Accordingly, these findings suggested that the reciprocal inhibition at the motoneuronal level did not largely contribute to the present suppression, and that Vsac suppression might occur at a premotor level.
The earliest and latest effective FEF stimulation for Vsac suppression were about 125 and about 130 ms after target onset (i.e., 55 and 50 ms before saccade onset), respectively. In the FEF, a visual stimulus activates visual neurons at latencies of about 90 ms (Bruce and Goldberg 1985), whereas movement neurons start firing about 150 ms after target onset (Bruce and Goldberg 1985) and about 100 ms before Vsac onset (Segraves and Park 1993). Taking into account the latencies of these neurons, it is safe to conclude that FEF stimulation suppressed neurons in the efferent pathway from the FEF to ocular motoneurons, rather than those in the afferent pathway from the retina to the FEF. Candidates for such suppression are the FEF, the SC, and the paramedian pontine reticular formation (PPRF). Inhibition of the contralateral FEF might be responsible for the suppression of ipsiversive Vsacs, since Schlag et al. (1998) showed that movement-related neurons in the FEF were inhibited by electrical stimulation of the contralateral FEF at a latency of 5–20 ms. The latencies of FEF-evoked Esacs ranged from 40 to 65 ms, with 45–55 ms being typical. Using much higher currents, Robinson and Fuchs (1969) found that FEF-Esacs had short latencies of 15–25 ms, and Bruce et al. (1985) reported Esac latencies of 20–60 ms. However, natural signals for Vsacs from the FEF take more time to generate saccades than electrically driven signals. Therefore the FEF stimulation must be given 45–85 ms before the onset of Vsacs for suppression of the contralateral FEF. Movement neurons in the FEF should have already started firing (100 ms before Vsac onset) at the time of the latest effective FEF stimulation for suppression (50 ms before Vsac onset). However, inhibition of contralateral FEF might be considered as a possible mechanism for suppression because the stimulation pulses may affect saccades on the tail of the reaction time distribution. The present data suggest that the SC and PPRF are more likely candidates for the present FEF suppression. Deeper-layer neurons in the SC show burst spike activity 30–50 ms before saccade onset (Sparks et al. 1976; Wurtz and Goldberg 1972). Electrical stimulation of the SC elicits Esacs with a latency of 20–30 ms (Azuma et al. 1996; Robinson 1972; Schiller and Stryker 1972).
As discussed previously, the synchronous suppression of horizontal and vertical components of Vsacs may be attributed to the suppression of neuronal activity in the SC. Direct projection from the FEF to the ipsilateral SC has been well established (Künzle and Akert 1977; Segraves and Goldberg 1987), and inhibitory connections have been reported between the bilateral superior colliculi (Munoz and Istvan 1998). Schlag-Rey et al. (1992) reported that FEF microstimulation that was suprathreshold for evoking saccades of a given vector inhibited SC saccade cells encoding a different vector. Schiller et al. (1987) showed that ablation of the SC increased the latency of contraversive saccades and the proportion of express saccades ipsiversive to the collicular lesion, probably as a consequence of the disruption of intercollicular inhibitory connections. This suggestion is consistent with the present finding that FEF-associated suppression of Vsacs may occur at the level of the SC. Stanford et al. (1996) suggested that there must be at least 3 independent readouts of collicular activity: one that specifies saccade direction and amplitude, a second that specifies the speed of the movement, and a third that triggers the movement. The FEF suppression of ipsilateral saccades could occur by inhibiting this third mechanism in the ipsilateral SC, so that inhibition of omnipause neurons (OPNs) will be suppressed at the onset of saccades. Although the exact inhibitory neural connections within the SC are not yet fully understood, these previous findings suggest that the SC may contribute at least in part to the present FEF-associated suppression. Input from the basal ganglia may be another source of inhibition in the SC. Activation of the FEF inhibits neurons in the substantia nigra reticulata (SNr) by caudate neurons, thereby disinhibiting ipsilateral SC neurons (Hikosaka and Wurtz 1983), and therefore may influence inhibition of the contralateral SC indirectly by the intercollicular connection (Munoz and Istvan 1998; Schiller et al. 1987).
Ipsilateral EBNs in the PPRF may be suppressed by FEF stimulation. Stimulation of the PPRF produces saccadelike eye movements at an EMG latency of about 3 ms (Cohen and Komatsuzaki 1972). EBNs show a burst of activity 8–10 ms before saccade onset (Luschei and Fuchs 1972). Stimulation of the FEF may activate contralateral EBNs, which produce depolarization subthreshold for generating spikes in contralateral abducens motoneurons. The same FEF stimulation may also activate contralateral IBNs, which in turn produce hyperpolarization in ipsilateral EBNs (Strassman et al. 1986; Yoshida et al. 1982). This hyperpolarization may reduce the number of ipsilateral firing EBNs, which in turn causes membrane potentials of ipsilateral abducens motoneurons to become subthreshold for firing. Therefore this IBN inhibition of EBNs may be responsible for the suppression of ipsiversive Vsacs, if it is much stronger than on abducens motoneurons. Another possibility is the inhibition of EBNs by OPNs. EBNs receive tonic inhibition from OPNs at rest (Keller 1974; Ohgaki et al. 1987). Stimulation of the FEF, which evokes Esacs, inhibits OPNs and thereby disinhibits both EBNs and IBNs (Segraves 1992). However, stimulation of the FEF may activate OPNs directly (Stanton et al. 1988) or indirectly by the SC (Gandhi and Keller 1997; Langer and Kaneko 1990; Paré and Guitton 1994; Raybourn and Keller 1977), and these OPNs may inhibit EBNs ipsilateral to the FEF. This interpretation may fit with the finding that stimulation of the rostral pole of the SC mainly suppresses ipsilateral saccades, although the suppression occurs on bilateral saccades (Paré and Guitton 1994). It is tacitly assumed that OPNs project bilaterally to EBNs and IBNs, but as yet there is no experimental evidence to support the bilateral inhibition by single OPNs. Instead, we have evidence that single OPNs project to EBN and IBN areas mainly on the opposite side (Ohgaki et al. 1987; Strassman et al. 1987). Thus these OPNs may suppress the initiation of ipsiversive saccades if they are activated directly or by the SC by FEF stimulation.
FEF stimulation suppressed only the initiation of Vsacs and Msacs, and not the metrics of the saccades. The stronger suppression of ipsiversive saccades with larger amplitudes suggests that this mechanism may make larger saccades less likely to occur during fixation, but may help generate small catch-up saccades during ipsiversive smooth pursuit eye movements. The stronger suppression of ipsiversive saccades with the more ipsilateral initial eye position suggests that ipsiversive centripetal saccades may occur more easily than ipsiversive centrifugal saccades during fixation. This might contribute to the eye-centering mechanism (Bender 1955). Types of corticofugal neurons that are responsible for FEF suppression of ipsilateral saccades remain uninvestigated. At least 2 groups of neurons so far reported in the FEF might be candidates for FEF suppression: saccade-related neurons and fixation neurons. Smooth pursuit–related neurons might not be responsible for this suppression, since stimulation of the smooth pursuit–related subregion of the FEF evokes ipsiversive smooth pursuit eye movements (MacAvoy et al. 1991). Depending on whether this suppression is related to visual fixation or to reciprocal inhibition for saccade generation, fixation-related output neurons or saccade-related output neurons might be involved for this suppression. A lesion of the FEF in human patients produced an increased frequency of express saccades, especially saccades directed toward the side of the lesion (Braun et al. 1992). In the monkey, FEF inactivation increased the frequency of premature saccades to ipsilateral targets (Dias and Segraves 1999; Sommer and Tehovnik 1997). These findings suggest the impairment of the suppressive function of fixation neurons in the FEF, and that fixation neurons are more likely to be involved in the present FEF-associated ipsilateral suppression. Further studies are required to identify the exact neural mechanisms that underlie the FEF-associated suppression of ipsiversive Vsacs and Msacs.
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Address for reprint requests and other correspondence: Y. Shinoda, Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan (E-mail: yshinoda.phy1{at}med.tmd.ac.jp).
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|---|
Azuma M, Nakayama H, and Suzuki H. Suppression of visually triggered saccades by electrical stimulation of the monkey frontal eye field (Abstract). J Physiol Soc Jpn 48: 266, 1986.
Bender MB. The eye-centering system. AMA Arch Neurol Psychiatry 73: 685–699, 1955.[Medline]
Bizzi E. Discharge of frontal eye field neurons during saccadic and following eye movements in unanesthetized monkeys. Exp Brain Res 6: 69–80, 1968.[Web of Science][Medline]
Braun D, Weber H, Mergner TH, and Schulte-Mönting J. Saccadic reaction times in patients with frontal and parietal lesions. Brain 115: 1359–1386, 1992.
Bruce CJ and Goldberg ME. Primate frontal eye fields. I. Single neurons discharging before saccades. J Neurophysiol 53: 603–635, 1985.
Bruce CJ, Goldberg ME, Bushnell MC, and Stanton GB. Primate frontal eye fields. II. Physiological and anatomical correlates of electrically evoked eye movements. J Neurophysiol 54: 714–734, 1985.
Burman DD and Bruce CJ. Suppression of task-related saccades by electrical stimulation in the primate's frontal eye field. J Neurophysiol 77: 2252–2267, 1997.
Büttner-Ennever JA and Büttner U. The reticular formation. In: Reviews of Oculomotor Research, vol. 2. Neuroanatomy of the Oculomotor System, edited by Büttner-Ennever JA. Amsterdam: Elsevier, 1988, p. 119–175.
Cohen B and Komatsuzaki A. Eye movements induced by stimulation of the pontine reticular formation: evidence for integration in oculomotor pathways. Exp Neurol 36: 101–117, 1972.[CrossRef][Web of Science][Medline]
Dias EC and Segraves MA. Muscimol-induced inactivation of monkey frontal eye field: effects on visually and memory-guided saccades. J Neurophysiol 81: 2191–2214, 1999.
Eccles JC. The Physiology of Synapses. Berlin: Springer-Verlag, 1964.
Fuchs AF, Kaneko CRS, and Scudder CA. Brainstem control of saccadic eye movements. Ann Rev Neurosci 8: 307–337, 1985.[CrossRef][Web of Science][Medline]
Gandhi NJ and Keller EL. Spatial distribution and discharge characteristics of superior colliculus neurons antidromically activated from the omnipause region in monkey. J Neurophysiol 78: 2221–2225, 1997.
Goldberg ME, Bushnell MC, and Bruce CJ. The effect of attentive fixation on eye movements evoked by electrical stimulation of the frontal eye fields. Exp Brain Res 61: 579–584, 1986.[CrossRef][Web of Science][Medline]
Grantyn A and Grantyn R. Synaptic actions of tectofugal pathways on abducens motoneurons in the cat. Brain Res 105: 269–285, 1976.[CrossRef][Web of Science][Medline]
Grantyn A and Grantyn R. Axonal patterns and sites of termination of cat superior colliculus neurons projecting in the tecto-bulbo-spinal tract. Exp Brain Res 46: 243–256, 1982.[Web of Science][Medline]
Guitton D, Buchtel HA, and Douglas RM. Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Exp Brain Res 58: 455–472, 1985.[Web of Science][Medline]
Hikosaka O and Wurtz RH. Visual and oculomotor functions of monkey substantia nigra pars reticulata. IV. Relation of substantia nigra to superior colliculus. J Neurophysiol 49: 1285–1301, 1983.
Izawa Y, Sugiuchi Y, and Shinoda Y. Neural organization from the superior colliculus to motoneurons in the horizontal oculomotor system of the cat. J Neurophysiol 81: 2597–2611, 1999.
Izawa Y, Suzuki H, and Shinoda Y. Suppression of saccades by stimulation of the frontal eye field (Abstract). Jpn J Physiol Suppl 51: S19, 2001.
Izawa Y, Suzuki H, and Shinoda Y. Suppression of visually and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. II. Suppression of bilateral saccades. J Neurophysiol 92: 2261—2273, 2004.
Keller EL. Participation of medial pontine reticular formation in eye movement generation in monkey. J Neurophysiol 37: 316–332, 1974.
Künzle H, and Akert K. Efferent connections of cortical area 8 (frontal eye field) in Macaca fascicularis. A reinvestigation using the autoradiographic technique. J Comp Neurol 173: 147–164, 1977.[CrossRef][Web of Science][Medline]
Langer TP and Kaneko CRS. Brainstem afferents to the oculomotor omnipause neurons in monkey. J Comp Neurol 295: 413–427, 1990.[CrossRef][Web of Science][Medline]
Latto R and Cowey A. Visual field defects after frontal eye-field lesions in monkeys. Brain Res 30: 1–24, 1971.[CrossRef][Web of Science][Medline]
Luschei ES and Fuchs AF. Activity of brain stem neurons during eye movements of alert monkeys. J Neurophysiol 35: 445–461, 1972.
MacAvoy MG, Gottlieb JP, and Bruce CJ. Smooth-pursuit eye movement representation in the primate frontal eye field. Cereb Cortex 1: 95–102, 1991.
Munoz DP and Istvan PJ. Lateral inhibitory interactions in the intermediate layers of the monkey superior colliculus. J Neurophysiol 79: 1193–1209, 1998.
Ohgaki T, Curthoys IS, and Markham CH. Anatomy of physiologically identified eye-movement-related pause neurons in the cat: pontomedullary region. J Comp Neurol 266: 56–72, 1987.[CrossRef][Web of Science][Medline]
Paré M and Guitton D. The fixation area of the cat superior colliculus: effects of electrical stimulation and direct connection with brainstem omnipause neurons. Exp Brain Res 101: 109–122, 1994.[Web of Science][Medline]
Precht W, Schwindt PC, and Magherini PC. Tectal influences on cat ocular motoneurons. Brain Res 82: 27–40, 1974.[CrossRef][Web of Science][Medline]
Raybourn MS and Keller EL. Colliculoreticular organization in primate oculomotor system. J Neurophysiol 40: 861–878, 1977.
Robinson DA. Eye movements evoked by collicular stimulation in the alert monkey. Vision Res 12: 1795–1808, 1972.[CrossRef][Web of Science][Medline]
Robinson DA and Fuchs AF. Eye movements evoked by stimulation of frontal eye fields. J Neurophysiol 32: 637–648, 1969.
Schiller PH, Sandell JH, and Maunsell JHR. The effect of frontal eye field and superior colliculus lesions on saccadic latencies in the rhesus monkey. J Neurophysiol 57: 1033–1049, 1987.
Schiller PH and Stryker M. Single-unit recording and stimulation in the superior colliculus of the alert rhesus monkey. J Neurophysiol 35: 915–924, 1972.
Schlag J, Dassonville P, and Schlag-Rey M. Interaction of the two frontal eye fields before saccade onset. J Neurophysiol 79: 64–72, 1998.
Schlag-Rey M, Schlag J, and Dassonville P. How the frontal eye field can impose a saccade goal on superior colliculus neurons. J Neurophysiol 67: 1003–1005, 1992.
Segraves MA. Activity of monkey frontal eye field neurons projecting to oculomotor regions of the pons. J Neurophysiol 68: 1967–1985, 1992.
Segraves MA and Goldberg ME. Functional properties of corticotectal neurons in the monkey's frontal eye field. J Neurophysiol 58: 1387–1419, 1987.
Segraves MA and Park K. The relationship of monkey frontal eye field activity to saccade dynamics. J Neurophysiol 69: 1880–1889, 1993.
Sommer MA and Tehovnik EJ. Reversible inactivation of macaque frontal eye field. Exp Brain Res 116: 229–249, 1997.[CrossRef][Web of Science][Medline]
Sparks DL, Holland R, and Guthrie BL. Size and distribution of movement fields in the monkey superior colliculus. Brain Res 113: 21–34, 1976.[CrossRef][Web of Science][Medline]
Sparks DL, Mays LE, and Porter JD. Eye movements induced by pontine stimulation: interaction with visually triggered saccades. J Neurophysiol 58: 300–318, 1987.
Stanford TR, Freedman EG, and Sparks DL. Site and parameters of microstimulation: evidence for independent effects on the properties of saccades evoked from the primate superior colliculus. J Neurophysiol 76: 3360–3381, 1996.
Stanton GB, Goldberg ME, and Bruce CJ. Frontal eye field efferents in the macaque monkey. II. Topography of terminal fields in midbrain and pons. J Comp Neurol 271: 493–506, 1988.[CrossRef][Web of Science][Medline]
Strassman A, Evinger C, McCrea RA, Baker RG, and Highstein SM. Anatomy and physiology of intracellularly labelled omnipause neurons in the cat and squirrel monkey. Exp Brain Res 67: 436–440, 1987.[Web of Science][Medline]
Strassman A, Highstein SM, and McCrea RA. Anatomy and physiology of saccadic burst neurons in the alert squirrel monkey. II. Inhibitory burst neurons. J Comp Neurol 249: 358–380, 1986.[CrossRef][Web of Science][Medline]
Suzuki H and Azuma M. A glass-insulated "elgiloy" microelectrode for recording unit activity in chronic monkey experiments. Electroencephalogr Clin Neurophysiol 41: 93–95, 1976.[CrossRef][Web of Science][Medline]
Suzuki H and Azuma M. Prefrontal neuronal activity during gazing at a light spot in the monkey. Brain Res 126: 497–508, 1977.[CrossRef][Web of Science][Medline]
Suzuki H and Azuma M. Topographic studies on visual neurons in the dorsolateral prefrontal cortex of the monkey. Exp Brain Res 53: 47–58, 1983.[Web of Science][Medline]
Suzuki H and Azuma M. A reliable marking technique for identification of recording and stimulating sites in the brain. J Electrophysiol Tech 14: 121–124, 1987.
Tanaka M and Fukushima K. Neuronal responses related to smooth pursuit eye movements in the periarcuate cortical area of monkeys. J Neurophysiol 80: 28–47, 1998.
Welch K and Stuteville P. Experimental production of unilateral neglect in monkeys. Brain 81: 341–347, 1958.
Wurtz RH. Visual receptive fields of striate cortex neurons in awake monkeys. J Neurophysiol 32: 727–742, 1969.
Wurtz RH and Goldberg ME. Activity of superior colliculus in behaving monkey. III. Cells discharging before eye movements. J Neurophysiol 35: 575–586, 1972.
Wurtz RH and Mohler CW. Enhancement of visual responses in monkey striate cortex and frontal eye fields. J Neurophysiol 39: 766–772, 1976.
Yoshida K, McCrea R, Berthoz A, and Vidal PP. Morphological and physiological characteristics of inhibitory burst neurons controlling horizontal rapid eye movements in the alert cat. J Neurophysiol 48: 761–784, 1982.
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