1Department of Physiology,
Mushiake, Hajime,
Naotaka Fujii, and
Jun Tanji.
Microstimulation of the lateral wall of the intraparietal sulcus
compared with the frontal eye field during oculomotor tasks. We compared the effects of intracortical microstimulation (ICMS) of the
lateral wall of the intraparietal sulcus (LIP) with those of ICMS of
the frontal eye field (FEF) on monkeys performing oculomotor tasks.
When ICMS was applied during a task that involved fixation, contraversive saccades evoked in the LIP and FEF appeared similar. When
ICMS was applied to the FEF at the onset of voluntary saccades, the
evoked saccades collided with the ongoing voluntary saccade so that the
trajectory of voluntary saccade was compensated by the stimulus. Thus
the resultant saccade was redirected and came close to the endpoint of
saccades evoked from the fixation point before the start of voluntary
saccade. In contrast, when ICMS was applied to the LIP at the onset of
voluntary saccades, the resultant saccade followed a trajectory that
was different from that evoked from the FEF. In that case, the
colliding saccades were redirected toward an endpoint that was close to
the endpoint of saccades evoked when animals were already fixating at
the target of the voluntary saccade. This finding suggests that the
colliding saccade was directed toward an endpoint calculated with
reference to the target of the voluntary saccade. We hypothesize that,
shortly before initiation of voluntary saccades, a dynamic process
occurs in the LIP so that the reference point for calculating the
saccade target shifts from the fixation point to the target of a
voluntary saccade. Such predictive updating of reference points seems
useful for immediate reprogramming of upcoming saccades that can occur in rapid succession.
As a result of recent studies, the lateral
intraparietal area (LIP) of the primate cerebral cortex is now thought
to be involved in oculomotor control. Neurons in the LIP are active
before saccadic eye movements (Andersen 1995 The technique of intracortical microstimulation (ICMS) is useful in
revealing the way in which output from the cortical oculomotor areas
influences oculomotor behavior, especially if the ICMS is applied
during the performance of a variety of oculomotor tasks (Fujii
et al. 1995 We studied the effects of ICMS in both hemispheres of two
monkeys (Macaca fuscata) during the performance of the
trained oculomotor tasks. Eye positions and movements were monitored
with an infrared monitor system with a time resolution of 4 ms. The
animal sat in a primate chair with its head and arms restrained, facing
a panel equipped with five light-emitting diodes (LEDs). The central LED was directly in front of the animal, and the other four LEDs were
9.5 cm (20° of visual angle) above, below, left, and right of the
central LED. The animals were trained to perform two tasks: a fixation
task and a memory-guided saccade task. In the fixation task, an LED
selected randomly from the five LEDs was illuminated as the target of
fixation, and the monkey was required to fixate on the target. If
fixation was maintained for 1.5-2.0 s within a 2° fixation window, a
reward of fruit juice was delivered. In the memory-guided saccade task,
the monkeys were first required to maintain fixation on the fixation
LED for 1.0-1.5 s. After this, a second LED that served as a cue for a
future saccade target was illuminated for 100 ms. If the animals
maintained fixation on the original LED for an additional 500-800 ms,
the original LED was dimmed. This served as a GO signal.
The monkeys were rewarded if the second LED was captured with a saccade
within 400 ms of the GO signal.
While the monkeys performed these tasks, we applied ICMS (330 Hz,
10-50 negative pulses, 0.2-ms duration) under two different conditions. In the first, ICMS was delivered during the fixation task
(fixation ICMS), 500 ms after the onset of fixation. In the second, the
initiation of ICMS was timed to occur shortly before or to coincide
with the onset of the memory-guided saccade (saccade-onset ICMS).
We penetrated the LIP, where ICMS evoked saccades with currents of
30-120 µA. The FEF is located in the anterior wall of the arcuate
sulcus, where saccades were elicited by ICMS with low currents (<50
µA). We used two measures for the quantitative analysis of evoked
saccades. First, to quantify the effect of eye position on saccade
vectors, a regression analysis was performed with the method reported
by Russo and Bruce (Fujii et al. 1998 We used 96 stimulus sites to localize the FEF to the anterior wall
of the arcuate sulcus. There were 58 stimulus sites in the LIP (Fig.
1, A and
B), lateral to the transitional border area defined by Thier
and Andersen (1996)
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
;
Snyder et al. 1997
), and electrical stimulation of the
LIP evokes saccadic eye movements (Thier and Andersen
1996
). Anatomically, the LIP is connected with the frontal eye
field (FEF) (Stanton and Bruce 1995
) and brain stem
oculomotor areas. These reports led to the question of how the two
cortical oculomotor areas, the LIP and the FEF, differ in their control over saccadic eye movements.
; Schlag and Schlag-Rey 1990
). Thus
we attempted to compare the properties of saccades evoked by
microstimulation of the LIP and FEF under two different conditions. In
the first condition, we analyzed saccade vectors evoked by stimulation
of the two areas during a task involving eye fixation and compared the
effects of eye position on the evoked saccades. In the second, we
applied stimulation while monkeys were performing an oculomotor task
that produced saccades directed toward memorized targets. By applying
stimulation shortly before or at the onset of voluntary saccades, we
compared saccade trajectories evoked in the LIP and FEF.
METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
; Russo and Bruce 1993
). According to a linear regression model, the size of evoked saccades E(P) is expressed as
E(P) = EC + (R × P), where EC is constant saccade vector for each
stimulation site, P is initial eye position, and
R is regression coefficient. If the vector of evoked saccade
is not affected by the initial eye position (fixed vector),
R is close to 0, and E(P) = EC. On the other hand, if the evoked saccades converge on a
point (converging vector), E(P) + P = EC, and R is close to
1.
Second, we estimated the point of origin of evoked saccades colliding
with voluntary saccades (evoked by saccade-onset ICMS) by using a
method devised by Schlag for the analysis of colliding saccades in the
FEF (Schlag and Schlag-Rey 1990
). This analysis was
based on the assumption that the endpoints of the colliding saccades
could be determined by the vectorial displacement from reference
positions that traversed the trajectory of the voluntary saccades. The
reference positions were calculated by subtracting the vectors of
saccades evoked during periods of fixation from the endpoints of the
colliding saccades. The recording sites were verified by histological
analysis (Mushiake 1997
).
RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
. We first examined the effects of eye positions on
evoked saccades from the LIP and the FEF to see whether there was any
significant difference in eye position effects in our sampled data from
the LIP and FEF. Saccades evoked by fixation ICMS of the LIP were
contraversive and appeared similar to saccades evoked form the FEF. To
examine the effects of eye position on evoked saccades in the LIP, the
horizontal and vertical regression coefficients were plotted in Fig.
1C. The mean (± SD) values were
0.14 ± 0.13 and
0.10 ± 0.11. These values indicated that evoked saccades in our
data were only moderately influenced with eye position signals.
Statistically, the eye position effects in the FEF and LIP were not
significantly different. Although detailed studies of eye position
effects on saccades evoked by ICMS of the LIP were not attempted in
this study (cf. Kurylo and Skavenski 1991
; Shibutani et al. 1984
),
these data showed that we surveyed the portion of the intraparietal
cortex where the position effects were not much different from those
observed in the FEF. Thus we did not study the ICMS effects in the
intercalated zone (Thier and Andersen 1996
) of the
intraparietal cortex where the eye position effects are prominent. The
latencies of evoked saccades of our samples were also statistically not
different in the LIP (55.7 ± 7.7 ms) and FEF (57.3 ± 10.0 ms).
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Fig. 1.
A: top view of the cerebral cortex showing the location
of the stimulus sites in the frontal eye field (FEF) (left) and lateral
wall of the intraparietal sulcus (LIP) (right). B:
points of microelectrode entry used for stimulation of the right LIP
are shown in an enlarged view. Saccades were elicited from the lateral
wall of the intraparietal sulcus (IPS). C: distribution
of horizontal and vertical regression coefficients calculated from
saccades evoked from the LIP at 19 penetration sites (cf. Russo and
Bruce 1993 ). D, left panels: trajectories
of saccades evoked from 3 fixation points (FP0-FP3) by fixation
intracortical microstimulation (ICMS) in FEF (top) and
LIP (bottom). D, right
panels: trajectories of saccades evoked by saccade-onset ICMS
in FEF (top) and LIP (bottom). Four
examples of saccade trajectories colliding on voluntary saccades
directed to 2 targets (T1 and T2) are shown. To the right of each
panel, the relationship between the colliding saccades and vectors of
saccades evoked by fixation ICMS from the fixation point (FP0) and from
two targets of voluntary saccades (T1 and T2) is drawn.
Colliding saccades were analyzed in the FEF and LIP in the two monkeys.
As reported previously, when ICMS was delivered in the FEF at the onset
of a voluntary saccade (saccade-onset ICMS), the evoked saccade
collided with the ongoing voluntary saccade. The colliding saccades
were directed toward the endpoints (E0) of saccades evoked by fixation
ICMS for each fixation point (Fig. 1D, top
right). In other words, the initial part of an ongoing voluntary
saccade was compensated by the saccade-onset ICMS. The properties of
these compensatory saccades observed in the FEF were consistent with
previous reports (Dassonville et al. 1992; Schlag
and Schlag-Rey 1990
). In contrast, when saccade-onset ICMS was
delivered in the LIP, the evoked colliding saccade behaved differently,
as shown in Fig. 1D (bottom right). Compensation for the initial part of the voluntary saccade was not observed in the
LIP. Instead the colliding saccades were first directed toward the
target of voluntary saccades (T1 or T2), and the evoked saccade was
subsequently directed toward an endpoint (E1 or E2). The endpoint of
colliding saccade corresponded to the endpoint (E1 or E2) of saccades
evoked from the target of voluntary saccades by fixation ICMS (see Fig.
1D, left). Thus the colliding saccades evoked in
the FEF and LIP terminated at entirely different endpoints.
We further examined saccade trajectories evoked in the FEF and LIP by changing initial eye positions and direction of voluntary saccades. As shown in the Fig. 2A, left panel, saccade-onset ICMS was delivered to the left FEF when voluntary saccades were directed from the central fixation point (F0) to four peripheral targets (T1-T4). The resultant saccades were redirected and came close to the endpoint (E0) of saccades evoked by fixation ICMS from the central fixation point (F0), regardless of where the targets of voluntary saccades were located, and similarly in Fig. 2A, right panel. Four evoked saccades collided with voluntary saccades from the peripheral fixation points (F1-F4) toward the central target (T0). Colliding saccades were redirected toward the endpoints (E1-E4) of saccades evoked from the peripheral fixation points by fixation ICMS. These results indicated that the endpoint of evoked saccades in the FEF was determined with reference to fixation points. On the other hand, saccade-onset ICMS was delivered to the LIP, when voluntary saccades were directed from the central fixation point (F0) to peripheral targets. As shown in Fig. 2B (left), trajectories of colliding saccades were redirected toward endpoints (E1-E4) of saccades evoked from the targets (T1-T4) of voluntary saccades by fixation ICMS. When voluntary saccades started from four peripheral fixation points to an central target (Fig. 2B, right), the colliding saccades evoked by saccade-onset ICMS were redirected to the endpoint (E0) of saccades evoked from the central target point (F0) by fixation ICMS. These results indicated that endpoints of evoked saccades in the LIP were determined with reference to the target of voluntary saccades.
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In the LIP, when ICMS was delivered at the same time as the
GO-signal appeared (~250 ms before the onset of a
voluntary saccade), the evoked saccades appeared to be fixed vector and
were identical to the saccades evoked by fixation ICMS. These saccades
differ from saccades evoked by saccade-onset ICMS. This difference
suggests that dynamic alterations occurred in the LIP and/or its output structures during the reaction interval between the appearance of the
GO-signal and the onset of a saccade, altering the effect of ICMS. To determine exactly how and when the fixed vector saccades are transformed to colliding saccades during the reaction interval, we
systematically applied ICMS at various times between the appearance of
the GO-signal and the onset of a voluntary saccade
(presaccade ICMS). We found that the evoked saccades and the intended
saccades interacted, giving rise to the interactive saccades shown in
Fig. 2C. The endpoint of the evoked saccades shifted
gradually, depending on the length of time that the ICMS preceded the
onset of the saccade. At greater intervals (30 ms to
74 ms), the
evoked saccade was directed toward an endpoint (E1-E4) that was closer
to the endpoint of the saccade elicited at the fixation point. Next we determined the reference points (R1-R4) for interactive saccades evoked in the LIP. As shown in Fig. 2C, we did this by
drawing a line from the endpoint of the interactive saccade
(Ei) parallel to the saccade vector evoked by the
saccade-onset ICMS. The reference point (Ri) was where this
line intersected the trajectory of the voluntary saccade. Subsequently,
we obtained data on 40 reference points calculated from saccades that
were evoked shortly before and after the onset of voluntary saccades.
In Fig. 3, we plotted the distance
between the reference point and the FP (expressed as a relative value
by dividing by the distance from the fixation point to the saccade
target) against the time relative to the saccade onset. We used an
exponential curve fitting method that was previously used to evaluate
the time course of changes in the reference point in the FEF
(Schlag and Schlag-Rey 1990
). The reference points
obtained by LIP stimulation (y) were fitted (goodness of fit
>90%) by the curve y = 0.992-0.051exp(
x/28.8),
where x is the time in milliseconds relative to the saccade
onset. Shifts in the reference points were initiated ~85 ms before
the onset of a saccade and completed just around its offset. In Fig. 3, we include the function y = 0.963-0.753exp(
x/76.9),
reported by Schlag for FEF stimulation data, with our LIP data. The
onset of a reference shift in the FEF is estimated to start 18 ms
before the saccade. Thus the reference shift in the LIP started 67 ms sooner than in the FEF.
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DISCUSSION |
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The main discovery of our study is that colliding saccades evoked
at the onset of voluntary saccades in the LIP terminated at positions
that were determined by the target of an intended saccade. This is
different from the colliding saccades evoked in the FEF, where the
endpoint is determined by the point of fixation. As Schlag demonstrated
in the FEF (1990), the compensation occurs in the initial part of the
saccade. This difference is not due to the latency of the evoked
saccades nor due to the eye position effect because the latencies and
eye position effects of saccades evoked in the LIP were not
significantly different from those of saccades evoked in the FEF.
During fixation, the reference point for saccade generation was the
fixation point. However, shortly before the initiation of a voluntary
saccade, the reference point shifted to the saccade target. Further
analysis suggested that the shift in the reference point from the
fixation point to the target of a voluntary saccade started 85 ms
before the onset of the voluntary saccade, and 67 ms ahead of the shift
in the FEF (Schlag and Schlag-Ray 1990
). We propose that
the LIP is involved in dynamic functional alterations that update the reference point before the initiation of a voluntary saccade. Updating
reference points in the LIP seems to be consistent with the idea of
predictive remapping in the LIP proposed by Duhamel et al.
(Colby et al. 1995
; Duhamel et al.
1992a
). The predictive remapping of visual responses was also
reported in the FEF by Umeno and Goldberg (1997)
. However, in their
studies, it was not clear whether there were any differences in
predictive visual responses of the LIP and FEF neurons. Quantitative
studies on the timing of anticipatory responses are necessary to
establish whether the process in the LIP may lead that of the FEF.
What is the implication of these findings for the role of the LIP in
controlling voluntary saccades? Our data suggest that the LIP is useful
in programming the second saccade in double-step saccades by an
anticipatory shift of the reference point. This view is consistent with
reports on parietal lesions (Colby et al. 1995;
Duhamel et al. 1992b
) in which patients had difficulty in generating the second saccade during double-step saccades. Neurons
in the LIP were selectively activated before the second saccade of
double-step saccades (Gnat and Andersen 1988
;
Mazzoni et al. 1996
). Reference points are important for
the vector calculation involved in the generation of multiple saccades.
As reviewed by Schlag and Schlag-Rey in 1990, different effects of
colliding saccades suggest that evoked saccades are directed to virtual targets from different internal reference points. If the reference point in the LIP is updated before the reference point in the FEF, the
LIP would use this advantage to reprogram the second saccade in a
double-step saccade before reprogramming occurred in the FEF.
Combining our results with those of previous studies, one aspect of LIP function seems to reside in anticipatory remapping of reference points for impending saccades. Further experiments are necessary to understand how the LIP is involved in the actual performance of oculomotor tasks.
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ACKNOWLEDGMENTS |
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We thank M. Kurama and Y. Takahashi for technical assistance.
This work was supported by PRESTO, JST, and the Ministry of Education, Science and Culture of Japan (09680809, 08279101, 09308032, and 08044236).
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FOOTNOTES |
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Address reprint requests to J. Tanji.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 24 August 1998; accepted in final form October 1998.
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