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1Department of Integrative Brain Science, Graduate School of Medicine, Kyoto University; and 2Kyoto Prefectural University of Medicine, Kyoto, Japan
Submitted 18 April 2006; accepted in final form 24 August 2006
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Krauzlis 2004; Lisberger et al. 1987; Thier and Ilg 2005).
In addition to the aspect of pursuit as a simple visuoocular reflex based on visuomotor processing, it is suggested that the gain of signal transformation from visual motion to motor command for generating pursuit is variable, depending on the subject’s behavioral state. The ocular responses evoked by a small brief movement of a tracking target (perturbation) were much larger when the perturbation was presented during ongoing pursuit than during fixation (Churchland and Lisberger 2002; Schwartz and Lisberger 1994). The magnitude of the response to the perturbation during pursuit increased as a function of ongoing pursuit velocity. These results suggest that the pursuit system possesses a mechanism that can modulate the gain of visuomotor transmission depending on the ongoing eye movement—fixation or pursuit—and that the gain modulation depends on the eye/target velocity. Further, it was previously reported that the gain is influenced by cognitive factors such as context and expectation (Keating and Pierre 1996; Krauzlis and Miles 1996; Tanaka and Lisberger 2000).
Recent experiments by our group showed that responses to the perturbation during fixating a target were larger when subjects (monkeys or humans) repeatedly performed smooth pursuit than when they repeatedly performed fixation or saccade (Kodaka and Kawano 2003; Tabata et al. 2004). The results suggest that the gain of visuomotor transmission is increased in advance of starting pursuit when the subjects experienced pursuit trials consecutively. The preparatory gain-increase was observed within several trials when the required eye movement in a block of trials was switched from saccade to pursuit (Tabata et al. 2005a). These results led us to assume that the gain of visuomotor transmission is modulated before pursuit eye movements in accordance with the recent experiences of pursuit and the gain modulation substantially influences the initial pursuit response to the target motion.
There is abundant knowledge about the pursuit initiation, which is associated with the visual properties of target motion (e.g., Carl and Gellman 1987; Krauzlis and Lisberger 1994b; Lisberger and Westbrook 1985; Lisberger et al. 1981; Morris and Lisberger 1987; Priebe et al. 2001; Tychsen and Lisberger 1986). However, to fully understand the neural processing of the smooth pursuit generation, it seems inevitable to clarify how the preparatory gain is modulated in relation to the recently experienced eye movements. To explore which parameters of past pursuit experiences play an essential role in modulating the preparatory gain, we recorded ocular responses to a brief perturbing motion of the target injected before the target motion for pursuit. One methodological advantage of observing the perturbation responses instead of the initial pursuit responses is that we can measure the gain of visuomotor transmission regardless of subsequent eye movements. By adopting this method, we can directly compare the internal gain state among different pursuit conditions, even in a no-pursuit condition (saccade trials in the present study). We systematically manipulated the parameters that might be correlated with the past pursuit experiences, i.e., duration of pursuit eye movements, required pursuit velocity, and timing of the perturbation injection. We found that before the pursuit initiation, triggered by the appearance of the tracking target, the gain of visuomotor transmission started increasing as a function of the time after the target appearance. A stable level of the gain, attained about 300 ms after the appearance of the tracking target, was dependent on the eye movements repeatedly generated in the recent past. The results were consistent with the idea that the gain of visuomotor transmission is modulated in accordance with the anticipated future need for the oculomotor control.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Kodaka et al. 2004) and thus will only briefly be given. Under pentobarbital sodium anesthesia and aseptic conditions, each monkey was implanted with a head holder, which allowed the head to be fixed in a standard stereotaxic position during the experiments, and with scleral search coils for measuring eye movements (Judge et al. 1980). The animals sat in a dark room and faced a translucent tangential screen (70 x 70 cm), which was placed 50 cm in front of the eyes. A green spot (0.5 deg) for stationary fixation and a red spot (0.5 deg) for smooth pursuit were generated with light-emitting diodes (LEDs) back-projected onto the screen and the horizontal and vertical positions of the latter were controlled by mirror galvanometers. The screen was not illuminated except for the two spots (no background illumination). In some behavioral paradigms, the animals were required to maintain their gaze on the central fixation spot (green LED) in spite of the appearance of the pursuit target (red LED). For this task, we used the following procedures to train them. First, they were trained to fixate on the green spot even if the red spot appeared at an eccentric position. Second, they were trained to move their gaze to the red spot and fixate it when the green spot was turned off. In the next step of training, the red spot began to move at a constant velocity simultaneously with the extinction of the green spot. The animals had to maintain fixation on the green spot until it was turned off and to begin tracking the red spot as soon as the green spot was turned off.
The tracking target (red spot) was placed 2 deg horizontally away from the central fixation spot (green spot) as its initial position because the animals tended to be irritated if the initial location of the tracking target was on the central fixation spot.
Experimental paradigms
The general procedure adopted in the present study is shown in Fig. 1A and examples of the velocity profiles of the tracking target and the ocular responses are shown in Fig. 1B. At the beginning of each trial, the animal had to look at the central fixation spot and maintain fixation until it went off. After 600–900 ms from the start of fixation, the tracking target appeared 2 deg from the central fixation spot either left or right. After a delay (in most cases 300 ms), the target briefly moved (perturbation). As shown in Fig. 1B, the velocity profile of the perturbation was one cycle of a 10-Hz sinusoidal wave. After the end of the perturbing motion, the target remained stationary for 100 ms, then started moving horizontally (left or right) at a constant velocity. We set the eye window of ±1.5 deg around the central fixation spot before it was turned off and around the target after the fixation spot disappeared. Thus the animal was required to keep its eyes on the central fixation spot (green spot) until the spot disappeared. The animal was then required to track the target (red spot) when it moved at a constant speed or to make a saccade and fixate the target when it remained stationary. After a delay (in most cases 800 ms), the target was turned off. The animal was rewarded with a drop of juice at the end of each trial. In the present study, we referred the duration between the target (red spot) appearance and the onset of the perturbation as POD (perturbation onset delay), the peak velocity of the perturbation as perturbation amplitude, the duration of the tracking target motion as target motion duration, and the velocity of the tracking target motion as target velocity. In the basic design of pursuit task, POD, perturbation amplitude, target motion duration, and target velocity were 300 ms, 10 deg/s (corresponding to the positional change of 0.3 deg), 800 ms, and 20 deg/s, respectively. To characterize the properties of the gain modulation, these parameters were manipulated in individual experiments, as described below. The initial target position, the direction of perturbation, and the target motion were randomized in each trial to minimize the anticipatory drift (Kowler and Steinman 1979a,b). The intertrial interval was always 2,000 ms. To characterize how each parameter affects the preparatory gain modulation, we manipulated the parameters for the individual experiments as follows.
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Each experiment consisted of eight blocks. For each block (80 trials), the target velocity was one of the following: 0, 2.5, 5, 10, 15, 20, 30, or 40 deg/s. Its order was in either increments or decrements. The animal was able to anticipate the required pursuit velocity because it was constant in each block. We collected a set of data (80 trials x 8 blocks, of either incremental or decremental order) in 1 day for each monkey. The results were consistent during both days irrespective of order; thus we mixed the data of both days for the analysis. The target motion duration, POD, and perturbation amplitude were 800 ms, 300 ms, and 10 deg/s, respectively.
We used one of seven maximum perturbation velocities: 2, 5, 10, 15, 20, 30, and 40 deg/s. Trials with different perturbation amplitudes were presented randomly within a block, but the target velocity was constant in each block (280 trials). Therefore the animals were exposed to the perturbation of various maximum velocities, although they could anticipate the velocity of upcoming pursuit. One experimental session consisted of three experimental blocks; in one session, the target velocities in the first, second, and third blocks were 0, 20, and 0 deg/s, and in the other they were 0, 5, and 0 deg/s.
The experiment consisted of two blocks. In one, the target velocity was 20 deg/s; the animals were required to pursue the moving target. In the other block, it was 0 deg/s; the animals had to execute a saccade after the central fixation spot was turned off and then to maintain fixation on the stationary target. For each block (640–940 trials), the PODs (one of these selected for each trial: 0, 25, 50, 100, 200, 300, 400, 600, or 800 ms) were mixed randomly. The two blocks of the experiment were designed to compare the effects of the POD on the preparatory gain when the animals repeatedly tracked the moving target with those when they executed saccades.
Data collection and analysis
The presentation of stimuli and the collection, storage, and display of data were controlled by a PC running the REX operating system (Hays et al. 1982). Eye movements were measured using the electromagnetic search coil technique (Fuchs and Robinson 1966). Voltage signals encoding the horizontal and vertical components of the eye position were passed through an analog filter (200 Hz) and digitized to a resolution of 12 bits and a sampling at 1 kHz. All data were stored and transferred to another PC for analysis using an interactive computer program based on Matlab (The MathWorks). The data were filtered by digital (33-point FIR, –3 dB at 30 Hz) filter before analysis.
We observed ocular responses elicited by a perturbation as a measure of the gain of visuomotor transmission (e.g., Schwartz and Lisberger 1994). We detected saccades based on the criteria eye velocity >50 deg/s and eye acceleration >500 deg/s2 (in some cases of monkey K, >1,000 deg/ s2). We rejected the data in the interval of 200 ms starting 100 ms before the onset of saccade. To evaluate the perturbation responses quantitatively, we calculated the mean eye velocity of 80-ms duration starting from 70 ms after perturbation onset (the period between two dotted lines drawn in Figs. 1B and 2). We regarded the mean eye velocity of all data in each subject over a 70-ms interval from the onset of the perturbation as a baseline and subtracted it from the ocular response to the perturbation.
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RESULTS |
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As shown in Fig. 2, A–D, the response profiles elicited by the perturbation were repeatable and closely time locked to the onset of the perturbation. The initial direction of the perturbation was rightward (Fig. 2, A and B) or leftward (Fig. 2, C and D) and the initial target position was left (Fig. 2, A and C) or right (Fig. 2, B and D). Herein, we referred to the conditions shown in Fig. 2, A, B, C, and D as L-R, R-R, L-L, and R-L (position–perturbation direction). The responses to the rightward perturbation were larger when the initial target position was left (Fig. 2A) than when it was right (Fig. 2B). In contrast, the responses to the leftward perturbation were smaller when the initial target position was left (Fig. 2C) than when it was right (Fig. 2D). As shown in Fig. 2, A–D, the perturbation caused asymmetric responses in most cases; the amplitude of the trough of the velocity profile was smaller than that of the peak. However, the velocity profiles of the perturbation response showed considerable variation in form from one direction to another and from one animal to another.
We calculated the mean eye velocity of 80-ms duration starting from 70 ms after the perturbation onset and showed the results in Fig. 2E with the same measurements for the other monkeys. The responses to the centripetal perturbation (black bar) were statistically larger than those to the centrifugal perturbation (white bar) in all cases (one-tailed t-test, P < 0.001). This is consistent with the result previously reported in human subjects (Tabata et al. 2004). Because the centrifugal responses were small especially in monkey U, we analyzed the responses to the centrifugal perturbation in only the two experiments: target velocity manipulation and POD manipulation.
Dependency on target motion duration
We compared perturbation responses when the duration of target motion for pursuit (target motion duration) was manipulated. One experiment consisted of three blocks: the target motion duration of the first and third blocks was 800 ms and that of the second block was manipulated (0, 50, 100, 200, 300, or 400 ms). The eye velocity profiles in Fig. 3A indicate a gradual increase of the responses to centripetal perturbation in accordance with the increase of target motion duration (monkey S). In the target motion duration = 0-ms condition, the fixation was repetitively required. The amplitudes of the responses in the second block (continuous lines) were smaller than those in the first and third blocks (broken lines, target motion duration = 800 ms). The amplitudes of responses in the second block of the target motion duration = 50-ms condition were also smaller than those in the first and third blocks (the target motion duration = 800 ms). However, the response amplitudes in the second block of the target motion duration = 100- and 200-ms conditions were almost the same as those in the first and third blocks. The velocity profiles of smooth pursuit eye movements in Fig. 3B indicate that the initial pursuit responses gradually increased with increases in target motion duration and the eye velocity profiles in the second block of the target motion duration = 200-ms condition were almost the same as the profiles in the first and third blocks (target motion duration = 800 ms), at least for the initial 200-ms part of the pursuit.
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), the amplitude of the perturbation response is a good measure of the gain of visual transmission for the pursuit initiation.
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We investigated the effect of the required pursuit velocity on the response amplitude to the perturbation before the start of pursuit. We compared the ocular responses elicited by the perturbation when the pursuit target velocity was manipulated. The superimposed eye velocity profiles elicited by the same perturbation (sinusoidal, maximum velocity 10 deg/s) shown in Fig. 6 indicate that the responses increased when the pursuit target velocity increased. The dependency of the perturbation response on the required pursuit velocity is further confirmed by the graph in Fig. 7, where the amplitude of the perturbation responses of three monkeys is plotted as a function of the required pursuit velocity. For the centripetal perturbation, the perturbation responses increased monotonically when the pursuit velocity increased (Fig. 7A). In all cases, the slopes of regression lines fitted to individual data are significantly different from zero (two-tailed t-test, P < 0.01). For the centrifugal motion, similar effects were observed, although the response amplitudes were generally smaller than those for the centripetal motion (Fig. 7B). In five cases (except for monkey U, L-L), the regression slopes were significantly different from zero (two-tailed t-test, P < 0.01). Thus the ocular responses varied depending on the required pursuit velocity, even if the visual input (perturbation) was identical. The results suggest that the pursuit system changes the gain of visuomotor transmission to prepare for the different pursuit velocities.
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To examine whether the repeated experience of a particular pursuit velocity causes the gain increase in the responses to the perturbations of various velocities, we measured the ocular responses to the perturbations of various peak velocities (perturbation amplitude). We carried out three consecutive experimental blocks—saccade block (first saccade), pursuit block, and saccade block (second saccade block)—and compared the perturbation responses among the blocks. Figure 8A shows the sample velocity profiles of the responses to the perturbation whose maximum velocity was 10 deg/s (monkey S, L-R), when the animal repeatedly performed saccades (gray and dashed lines) or 20 deg/s pursuits (black line). The responses in the pursuit block were larger than those in the saccade blocks. Similar results were observed in the other perturbation amplitudes (20, 30, and 40 deg/s for Fig. 8, B, C, and D, respectively), suggesting that preparation for an upcoming 20 deg/s pursuit affects the responses to the perturbation of the wide velocity range.
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Dependency on perturbation onset delay
We investigated the effects of the interval between the target appearance and the onset of perturbation [perturbation onset duration (POD); also see Fig. 1B] on the perturbation response. The size of perturbation response gradually increased with increases in POD when pursuit was repetitively required (pursuit block, Fig. 10A). In contrast, the perturbation response showed only a slight increase when saccade was repetitively required (saccade block, Fig. 10B). Results of the other perturbation direction and another monkey exhibited similar POD dependency (Fig. 11). The magnitude of the perturbation response gradually increased when the POD increased and reached a plateau at POD values of about 300–600 ms in the pursuit block (Fig. 11, A and C). Thus the increase of the gain of visuomotor transmission in preparing for upcoming pursuit depended on the delay after the target appearance. In contrast to the case of the pursuit block, the magnitude of perturbation responses was not sizably increased, regardless of the increase in POD (Fig. 11, B and D) in the saccade block. The statistical analysis showed that in most cases (except for POD = 0 ms of L-R and POD = 25 ms of R-L in monkey U) the perturbation responses were larger in the pursuit block than those in the saccade block (indicated by asterisks in Fig. 11, A and C, one-tailed t-test, P < 0.05).
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300-ms condition), the responses in the pursuit block were significantly larger than those in the saccade block. The results indicate that the system’s sensitivity to the centrifugal target motion was also increased with the increase of POD, when the animals repeatedly performed pursuit.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Temporal development of the preparatory gain modulation after the appearance of pursuit target
The results of the experiment in which the POD was manipulated suggest that the pursuit target must be visible before the start of pursuit to observe substantial perturbation responses. Krauzlis and Lisberger (1994b) investigated the effect of motion onset delay (MOD)—that is, the interval between the target appearance and the target motion requiring pursuit—on the initial acceleration of the pursuit. They found that the initial acceleration increased as a function of MOD and reached a plateau at MOD = 200 ms. This temporal property is similar to the temporal property of the POD effect in the present study. Therefore the change in initial acceleration observed in the previous study (Krauzlis and Lisberger 1994b) might be attributable to the difference in the gain of visuomotor transmission before pursuit.
Several lines suggest that the gain of visuomotor transmission in the pursuit system is influenced by attention. For example, a spatial deployment of attention influenced the oculomotor responses to the perturbation during ongoing tracking (Madelain et al. 2005). Besides, the saliency of the tracking target affected the initial responses of pursuit (Hashimoto et al. 2003; Miura et al. 2001). Therefore the temporal development of the gain in accordance with the POD might be related to the increase in attention level. Hashimoto et al. (2004) studied the temporal properties of the effect of saliency on the pursuit initiation by changing the interval between the presentation of the cue indicating the target position and the onset of the target motion (cue lead time). They found that the initial pursuit response was strongest when the cue lead time was about 160 ms and decayed near the no-cue level at 400 ms. They discussed that this temporal property was consistent with the transient component of attention (bottom-up attention) (Nakayama et al. 2004). In contrast, we report here that the perturbation response gradually increased with the increase of POD and it was strongest when the POD was 300–400 ms. This temporal increase might be attributable to the effect of the top-down or endogenous attention (Nakayama and Mackeben 1989; Theeuwes et al. 2004). We also observed that the perturbation responses showed little increase in the saccade blocks (Figs. 11, B and D and 12, B and D) even when the animals had to pay spatial attention to the target, similar to that in the pursuit block. The results suggest that the context of repetitive pursuit eye movements is necessary to observe the attentional effect on the perturbation responses.
The time course of the POD effect might be also influenced by the training. In most of the trials in the training and the present experiments, the POD was 300 ms and the onset of target motion requiring pursuit was 500 ms after the target appearance. Therefore the saturation at 400 ms as shown in Fig. 11, A and C might occur as a result of the expectation of target motion at that time. Further experiments are necessary to examine this possibility.
In addition, we found that the increase in the preparatory gain was observed when the animals repeatedly experienced initial 100–200 ms of the pursuit. This suggests the necessity of the experience of the initiation phase and the early part of the maintenance phase of the pursuit for setting the gain of visuomotor transmission to be higher. Because the duration of the perturbation was 100 ms in the present study, the perturbing target motion might also contribute to an increase in the preparatory gain. However, in comparison with the positional change of the target motion requiring pursuit (2 deg in most cases), that of the perturbing target motion was small (0.3 deg in most cases) and the target was finally located at the same position before the onset of the perturbation, so that no tracking was required of the animals. Therefore we consider that the effect of the perturbation itself was very small.
Velocity dependency of the preparatory gain modulation
In the present study, we showed that the pursuit system sets the gain at a higher state in the block when the animal repeatedly performed higher-speed pursuit. Some previous studies showed that the gain during ongoing pursuit increased depending on the target/eye velocity (Keating and Pierre 1996; Schwartz and Lisberger 1994). Our results suggest that a similar velocity dependency had already appeared before the start of pursuit when the animals were preparing for the pursuit of a specific velocity. The results again support the idea that the gain element is not controlled in a bistable "switch" fashion, but in a gradual manner (Churchland and Lisberger 2002; Keating and Pierre 1996; Schwartz and Lisberger 1994).
Besides, it was also reported that the initial eye acceleration is relatively higher for lower-velocity trials inserted in a block of high-velocity trials or lower for high-velocity trials inserted in a block of lower-velocity trials (Carl and Gellman 1987; Heinen et al. 2005; Kowler and Mckee 1987; Lisberger and Westbrock 1985). We suppose that these phenomena can be explained by the preparatory gain modulation in accordance with the required pursuit velocity. The gain before the start of pursuit might be set to the intermediate state if the monkeys and humans are exposed to more than two target velocities.
Why does the pursuit system adopt the higher initial gain under the condition that higher pursuit velocities are required? We propose that this velocity dependency of the gain before the start of pursuit contributes to compensation for the nonlinear properties that are inherent in the brain. For example, the neurons in the MT area (Lagae et al. 1993; Liu and Newsome 2003; Maunsell and van Essen 1983; Perrone and Thiele 2001; Rodman and Albright 1987) and the MST area (Kawano et al. 1984, 1994) exhibited the lower sensitivity to the higher image velocity of a small visual stimulus. These properties have also been postulated in the computational model of smooth pursuit (e.g., Dicke and Thier 1999; Krauzlis and Lisberger 1994a; Pack et al. 2001) and ocular following responses (Yamamoto et al. 2002). To achieve better facilitation of the initial pursuit drive for higher target motion, it seems necessary to conquer this nonlinearity by increasing the initial gain of visuomotor transmission. On the other hand, from a computational perspective, the neural pathway related to the pursuit generation structures a negative feedback control system with a long time delay; as a result the pursuit system should include less stability for higher internal gain. Accordingly, the gain before the start of pursuit may be optimally determined based on the trade-off criteria between facilitation and stability.
Comparison with the on-line gain control
In a classical experiment, Robinson (1965) reported that the artificial increases in the gain of negative feedback had little effect during fixation on a stationary target. However, the same increase produced large oscillations in eye velocity during the tracking of a moving target, and Robinson suggested that the fixation was not simply the zero-velocity pursuit and that the pursuit used specialized visuomotor pathways, which were not normally engaged during fixation. The difference between the responses to a given visual stimulus during maintained pursuit and during fixation was further studied later on. The framework of the "pursuit switch" (Goldreich et al. 1992; Grasse and Lisberger 1992; Morris and Lisberger 1987) or "on-line gain control" (Churchland and Lisberger 2002; Schwartz and Lisberger 1994) was suggested as a way to understand the results. In the framework, the difference in the gain incorporated in the visuomotor pathway can be explained by the difference between maintained pursuit and fixation. When the gain is high, the system functions as a pursuit system, but when low, it functions as a fixation system (Krauzlis and Lisberger 1994a; Krauzlis and Miles 1996).
The present results indicate that the gain of visuomotor transmission does not increase when the upcoming required movement is a saccade, but it does increase when the upcoming required movement is a pursuit. In other words, the gain is set at different levels dependent on the eye movement required in a particular block, although the ongoing behavior is a fixation. Therefore prior experience plays an essential role in modulating the preparatory gain for tracking movement. On the other hand, Schwartz and Lisberger (1994) reported that the amplitude of the perturbation response increased once the animal initiated the pursuit eye movement. Thus the pursuit system makes use of at least two types of gain modulation processes: First, the gain modulation that occurred within a single trial, which is mainly determined by ongoing behavior and, second, the gain modulation that is mainly determined based on previous experiences. We previously reported that the preparatory gain modulation was observed on a short timescale. The gain reached a new steady state within several trials when the saccade and pursuit blocks were changed (Tabata et al. 2005a) or when the pursuit blocks of different velocity were switched (5 and 30 deg/s; Tabata et al. 2005b). Based on these observations, we suggest that the pursuit system uses prior knowledge acquired through recent experiences, such as the required tracking velocity or the probability of required pursuit (Tabata et al. 2005a) to determine the initial level of the gain of visuomotor transmission.
In the study of Schwartz and Lisberger (1994), the perturbation response during ongoing pursuit was larger if the perturbation was presented later in the target motion and it reached a value about threefold larger than the perturbation response during fixation, 500 or 600 ms after the onset of target motion. In contrast, we found that the preparatory gain gradually increased along with the increase of the target motion duration, but it soon reached a plateau level in the condition of target motion duration = 200 ms (Fig. 4), suggesting that to fully increase the preparatory gain the later phase of the pursuit is not so important. These results might also provide evidence that the pursuit system uses two types of the gain modulation processes. The preparatory gain is set based on the recent pursuit experience and the gain probably further increases once after the start of pursuit to maintain good performance of pursuit.
Is there any difference in the waveform of the perturbation responses between before and after the start of pursuit? Schwartz and Lisberger (1994) used a perturbation similar to that in the present study (one cycle of a 10-Hz sine modulation of target velocity) and, in most cases, showed a biphasic change in eye velocity during ongoing pursuit. In the present study, however, the trough of the perturbation response was poor and the perturbation responses were generally monophasic. This difference might be attributable to the timing of the perturbation. We observed that the responses to perturbation injected during pursuit were similar to those shown in Schwartz and Lisberger (1994) (data not shown). In addition to the difference of the timing, however, some other factors might influence the waveform, such as the difference of the subject, the perturbation’s frequency, eccentricity, direction, and amplitude.
Comparison with other studies
There are studies showing that the gain of visuomotor transmission during fixation depends on the upcoming movement, either of fixation or pursuit. Keating and Pierre (1996) measured the ocular responses to the target oscillation during the fixation period in a successive target motion sequence. They found that the responses were larger when the human subjects anticipated the tracking of a sinusoidal target motion than when they anticipated the tracking of a saccade. The smooth eye movement evoked by the appearance of a cue was also larger when the monkeys were in the pursuit block than when they were in the saccade block, and the cue-evoked smooth eye movement became larger as the velocity of upcoming target motion increased (Tanaka and Lisberger 2000). These phenomena might be guided by the same mechanism as the preparatory gain control. All of these results support the idea that there are different levels of gain of visuomotor transmission before the start of eye movements, depending on whether upcoming tracking is required. Futhermore, Tanaka and Lisberger (2000) reported that the cue-evoked smooth eye movements were increased if a temporal "gap" between the offset of the fixation target and the appearance of the moving target was introduced. This gap might also increase the responses to perturbation when humans or animals repeatedly perform pursuit.
It has also been known that the anticipatory smooth eye movements could be induced when their direction was predictable (Barnes and Asselman 1991; Heinen et al. 2005; Kao and Morrow 1996; Kowler and Steinman1979a,b). The experimental results by using "remembered pursuit task" supported the idea that the pursuit system stored the velocity information as a short-term memory and generated anticipatory eye movements based on the stored trajectory information (Barnes and Asselman 1991; Barnes and Donelan 1999; Barnes et al. 1987). What is the relationship between the anticipatory eye movements and the gain of visuomotor transmission? In our study, we randomized the direction of pursuit in each trial to minimize the effect of directional anticipation. Therefore there is no direct evidence about how the gain of visuomotor transmission is set when the anticipatory drift occurs. However, there are several reports showing circumstantial evidence. First, the magnitude of the anticipatory eye movement was larger when the required tracking velocity was higher than when it was lower (Barnes and Asselman 1991; Heinen et al. 2005; Kao and Morrow 1996). This property is consistent with the gain modulation in accordance with the gain dependency on the required pursuit velocity in the present study. Second, the anticipatory eye movements were stronger in subjects who generated faster smooth pursuit, suggesting that the generation of the anticipatory and visually guided smooth pursuit was governed by a common mechanism (Kao and Morrow 1996). Although further research is clearly needed, the gain of visuomotor transmission in preparing for pursuit might be directionally biased when the direction of tracking is predictable.
Centripetal motion versus centrifugal motion
As shown in Figs. 2, 7, 11, and 12, the response amplitude to centripetal motion (L-R or R-L) was generally larger than the response to centrifugal motion (L-L or R-R). This phenomenon, so-called centripetal bias or toward–away asymmetry, was widely observed in previous studies investigating pursuit initiation (e.g., Lisberger 1998; Lisberger and Westbrook 1985; Miura et al. 2001; Tychsen and Lisberger 1986). Our results showed that the response amplitude to centrifugal motion increased with the increase in required pursuit velocity (Fig. 7) and the POD (Fig. 11), although the amplitude to centripetal perturbation was smaller. This suggests that the preparation for upcoming pursuit modulates the response gain to both motion directions (centripetal and centrifugal). Centripetal bias observed in the preparatory gain modulation agrees with the idea that the pursuit gain controller has directional asymmetry dependent on the initial target position (Lisberger 1998; Tanaka and Lisberger 2000).
Possible neural basis of the preparatory gain control
What is the neural basis that is implicated in the preparatory gain control of the pursuit system? There are several lines addressing this question. Smooth eye movement evoked by the perturbation during fixation was larger if the perturbation was given simultaneously with the electrical stimulation in the frontal eye field (FEF) (Tanaka and Lisberger 2001, 2002). It is also reported that the electrical stimulation in the supplemental eye field (SEF) facilitates the magnitude of pursuit initiation (Missal and Heinen 2001). These results suggest that the FEF and the SEF could participate in a modulation of the strength of the preparatory gain. In these areas, some neurons showed a gradual increase in activity during fixation before target motion (Heinen and Liu 1997; Tanaka and Fukushima 1998). Interestingly, the neurons in the FEF showed buildup activity even if the upcoming pursuit direction was unpredictable (Tanaka and Fukushima 1998). The authors described that the activity seemed to be related to the anticipation of target motion in any direction. The buildup activity might be related to the predictive nature of gain modulation. If so, we could expect that the same neurons will exhibit smaller activities when the animals are repeatedly performing saccade.
Komatsu and Wurtz (1989) studied the effect of electrical stimulation in the MT and MST areas on the pursuit system. They found that during fixation of a stationary target, the stimulation produced only a slight smooth eye movement. However, it produced eye acceleration during pursuit and its effectiveness increased as the speed of the pursuit increased. In other words, the artificial stimulation signals were modified by a signal related to the presence and speed of pursuit and then caused the eye movements. Based on these observations, Komatsu and Wurtz (1989) suggested that any input related to pursuit must have entered the system after the point of stimulation in the pursuit pathway. If so, the magnitude of the smooth eye movement evoked by electrical stimulation in the MT/MST area during fixation might be modulated in accordance with the expected future need for pursuit. We may be able to draw an outline of the entire neural substrate related to controlling the gain of visuomotor transmission by the combination of neurophysiological experiments and the behavioral paradigm proposed in the present study.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests and other correspondence: H. Tabata, Department of Integrative Brain Science, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto-shi, Kyoto 606-8501, Japan (E-mail: htabata{at}brain.med.kyoto-u.ac.jp)
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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