Department of Physiology, Medical Research Council Group in Sensory-Motor Neuroscience, Queen's University, Kingston, Ontario K7L 3N6, Canada
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ABSTRACT |
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Bell, A. H.,
S. Everling, and
D. P. Munoz.
Influence of Stimulus Eccentricity and Direction on
Characteristics of Pro- and Antisaccades in Non-Human Primates.
J. Neurophysiol. 84: 2595-2604, 2000.
The ability to inhibit reflexes in favor of goal-oriented behaviors is
critical for optimal exploration and interaction with our environment.
The antisaccade task can be used to investigate the ability of subjects
to suppress a reflexive saccade (prosaccade) to a suddenly appearing
visual stimulus and instead generate a voluntary saccade (antisaccade)
to its mirror location. To understand the neural mechanisms required to
perform this task, our lab has developed a non-human primate model. Two
monkeys were trained on a task with randomly interleaved pro- and
antisaccade trials, with the color of the central fixation point (FP)
instructing the monkey to either make a prosaccade (red FP) or an
antisaccade (green FP). In half of the trials, the FP disappeared 200 ms before stimulus presentation (gap condition) and in the remaining
trials, the FP remained visible (overlap condition) during stimulus
presentation. The effect of stimulus eccentricity and direction was
examined by presenting the stimulus at one of eight different radial
directions (0360°) and five eccentricities (2, 4, 8, 10, and
16°). Antisaccades had longer saccadic reaction times (SRTs), more
dysmetria, and lower peak velocities than prosaccades. Direction errors
in the antisaccade task were more prevalent in the gap condition. The difference in mean SRT between correct pro- and antisaccades, the
anti-effect, was greater in the overlap condition. The difference in
mean SRT between the overlap and the gap condition, the gap effect, was
larger for antisaccades than for prosaccades. The manipulation of
stimulus eccentricity and direction influenced SRT and the proportion
of direction errors. These results are comparable to human studies,
supporting the use of this animal model for investigating the neural
mechanisms subserving the generation of antisaccades.
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INTRODUCTION |
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Saccades are rapid eye movements
that serve to realign the fovea onto a stimulus of interest. We often
make saccades to novel visual stimuli that suddenly appear or move.
However, it is sometimes necessary to suppress this visual grasp reflex
(Hess et al. 1946) and instead generate a saccade to
alternative location. For example, when driving we must be able to
selectively ignore extraneous sights and sounds while maintaining
concentration on the road. This ability to selectively suppress saccade
reflexes in favor of goal-oriented behaviors is necessary for optimally
interacting with our environment. A task that probes this ability is
the antisaccade task, first introduced by Hallett
(1978)
, which requires the suppression of a reflexive saccade
(prosaccade) to a suddenly appearing visual stimulus and the generation
of a voluntary saccade (antisaccade) to the diametrically opposite
position. The importance of the antisaccade task as a clinical tool was
first demonstrated by Guitton and colleagues (1985)
, who
showed that patients with frontal lobe damage often had difficulty
suppressing reflexive prosaccades, a function essential to performing
the antisaccade task. Subsequently the antisaccade task has been used
to examine many neurological and psychiatric disorders (see
Everling and Fischer 1998
for review).
To understand the neural mechanisms responsible for the suppression of
reflexive saccades and generation of voluntary saccades in the
antisaccade task requires an animal model. Our lab (Everling and
Munoz 2000; Everling et al. 1998a
, 1999
) and
others (Amador et al. 1998
; Funahashi et al.
1993
; Gottlieb and Goldberg 1999
; Schlag-Rey et al. 1997
) have developed a non-human
primate model that permits recording neural activity from structures
known to be involved in the initiation and suppression of saccades
while awake, behaving monkeys perform the task. While previous studies have reported neural activities in the task, there has been little systematic study of the behavioral characteristics of antisaccades in
non-human primates. More importantly, there has been limited comparison
between monkey and human behavioral performance data, an important step
to validate these models. Such a step is essential to allow for the
translation of animal findings to human studies.
The purpose of the present study is to investigate the influence of
stimulus direction and eccentricity on the characteristics of pro- and
antisaccades in the non-human primate. The animals were therefore
trained to generate both pro- and antisaccades in response to stimuli
presented at one of eight different radial directions (0360°) and
five different eccentricities (2
16°). A further goal of this study
is to examine the effect of fixation state on saccade characteristics
and task performance. Thus the task was performed in both the gap and
overlap conditions (Saslow 1967
).
The data reveal that non-human primates trained on a task with randomly
interleaved pro- and antisaccade trials generate saccades with similar
characteristics to those seen in humans. Preliminary reports of these
data have been presented elsewhere (Bell et al. 1999).
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METHODS |
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Two adult male rhesus monkeys (Macaca mulatta,
weighing 7 and 10 kg) were used in this study. All procedures were
approved by the Queen's University Animal Care Committee and were in
accordance with the Canadian Council on Animal Care policy on the use
of laboratory animals. Animals were prepared for chronic behavioral experiments in a single surgical session. Eye movements were monitored using the magnetic search coil technique (Fuchs and Robinson
1966; Judge et al. 1980
). Scleral search coils
and a head-restraint device were implanted under ketamine/isoflurane
anesthetic in aseptic conditions (see Munoz and Istvan
1998
for details).
During training and experiments, the animals were seated in a primate chair (Crist Instruments) positioned 86 cm from a tangent screen spanning ±35° of the visual field in a dark, sound-attenuated room. Control of the behavioral paradigms and storage of eye position data were done using a 486 personal computer running a real-time data-acquisition software package (REX) (Hays et al. 1982). Horizontal and vertical eye positions were sampled at 500 Hz from one eye. Visual stimuli were generated by light-emitting diodes (LEDs, red and green, 0.3 cd/m2), which were back-projected onto the tangent screen and were positioned by reflecting the LEDs off two mirrors mounted on galvanometers oriented in orthogonal planes. The mirrors were located the same distance as the animal from the screen to correct for any tangent errors.
Behavioral paradigm
The monkeys were trained (see Training protocol) to
perform a paradigm with randomly interleaved pro- and antisaccade
trials (Fig. 1A). Between
trials, the screen was diffusely lit (1.0 cd/m2)
to prevent dark adaptation. The onset of each trial was signaled by the
removal of the background light and illumination of a central fixation
point (FP). The FP was presented for a period of 700-900 ms and was
either red, signifying a prosaccade trial, or green, signifying an
antisaccade trial. The FP was presented in two randomly interleaved
conditions: on half of the trials, the FP was extinguished 200 ms prior
to the appearance of the eccentric stimulus (gap condition; Fig.
1B) and in the remaining half of the trials, the FP remained
visible for the duration of the trial (overlap condition; Fig.
1C). In each block of trials, the eccentric red visual
stimulus appeared pseudorandomly at one of two diametrically opposite
locations for 600 ms. Stimuli were presented in blocks covering eight
different radial directions (0360°) and five different
eccentricities (2, 4, 8, 10, and 16°). Monkeys were given a liquid
reward if they maintained central fixation for the duration of the
fixation (700-900 ms) and gap period (200 ms), if applicable, and
generated a saccade in the proper direction (toward the stimulus in a
prosaccade trial and in the opposite direction in an antisaccade trial)
within 500 ms of eccentric stimulus appearance, and then maintained
fixation there for
200 ms. In antisaccade trials only, a green
stimulus was presented immediately after the saccade at the mirror
location of the red stimulus. Animals performed the task until fully
satiated at which point they were returned to their cages.
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Training protocol
The monkeys were trained, initially, to fixate a central red LED
for periods of 2,000 ms and perform a simple saccade task consisting
of a central red FP and a red stimulus of varying direction and
eccentricity that was presented in both the gap and overlap conditions.
The monkeys were required to generate a foveating saccade within 500 ms
of stimulus presentation to obtain a liquid reward. The on-line
accuracy window was kept relatively large (±5-10° in any direction
from the intended end point) at the start of the training and gradually
decreased to ±3o eccentricity around the central
FP and eccentric stimuli. Once the monkeys performed this task
correctly on 90% of trials, they were trained on an identical
task, this time using a green FP and a green eccentric stimulus. These
two tasks (red FP/red stimulus; green FP/green stimulus) were
eventually combined and randomly interleaved so that within a given
block of trials, the FP and stimulus would be either red or green.
The next stage of the training procedure consisted of having eccentric stimuli of both colors appearing in opposite hemifields for each trial regardless of the color of the FP. Therefore within a block of trials, there were both red and green stimuli present, and the FP was varied randomly between either red or green. The monkeys were required to direct a saccade to the eccentric stimulus whose color matched the FP. As the monkeys improved on this task to the point where they were >75% accurate, the green eccentric stimulus was removed from trials with the red FP (i.e., prosaccade trials), and a temporal delay was added between the appearance of the red and green stimuli for trials with a green FP (i.e., antisaccade trials). The delay was gradually increased from 0 to 600 ms at which point the green stimulus appeared 100 ms after the monkey's time allowance to generate an antisaccade had expired. The monkeys received a small reward if they delayed their saccade until the green stimulus appeared, whereas they received a large reward if, immediately after the appearance of the red stimulus, they generated a saccade to the location where the green stimulus would appear. Therefore to optimize reward on trials with a green FP, monkeys had to generate an anticipatory saccade to where the green stimulus would appear corresponding to the mirror position of the red stimulus which was visible. This represents the final form of the pro- and antisaccade task used in this study. Both monkeys were trained extensively on this task and reached a consistent level of performance (95% prosaccades; 80% antisaccades) before the data collection.
Data analysis
Data analysis was performed on a SunSparc2 workstation. Data
were first run through a saccade marking program, which was used to
identify the beginning and end of each saccade based on velocity and
acceleration template matching (Waitzman et al. 1991).
All marks were later verified by the experimenter and adjusted if necessary. Saccades with latencies <80 ms had a 50% probability of
being correct and were therefore rejected on the basis that they were
anticipations. Likewise, those with latencies above 500 ms were assumed
to be due to lack of attention and excluded. An off-line accuracy
criteria of ±45° in direction from the intended saccade direction at
any amplitude was used. This large acceptance window was necessary to
fully examine the characteristics of antisaccades, whose kinematics and
accuracy were considerably more variable than prosaccades. A direction
error in the antisaccade task was defined as a saccade that fell within
the acceptance window but on the stimulus side. Saccade gain was
defined as the ratio of saccade amplitude to stimulus eccentricity. A
gain above 1.0 indicated the saccade overshot the desired end point
(i.e., hypermetric), and a gain <1.0 indicated the saccade fell short
(i.e., hypometric). As both monkeys showed similar trends, data were
collapsed for the majority of the analyses. Statistical significance
was tested with Student's t-tests (P < 0.05).
All results are reported as means ± SE.
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RESULTS |
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Distribution of saccadic reaction times
The distribution of saccadic reaction times (SRTs) for both monkeys, collapsed across stimulus eccentricity and direction, are shown in Fig. 2 and are summarized in Table 1. Both monkeys generated prosaccades with significantly shorter SRTs compared with antisaccades for both the gap and overlap conditions (see Table 1; P < 0.001). Furthermore both monkeys had a larger anti-effect, defined as the difference in mean SRT between anti- and prosaccades, in the overlap condition compared with the gap condition (see Table 1). SRTs were also significantly shorter for both pro- and antisaccades generated in the gap condition compared with the overlap condition (gap effect; see Table 1; P < 0.001). Both monkeys showed a larger gap effect, defined as the difference in mean SRT between the gap and overlap conditions, for antisaccades compared with prosaccades (see Table 1).
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Monkey A showed a bimodal distribution of SRTs in the
prosaccade task, particularly in the gap condition (Fig. 2). The two modes correspond to saccades of express (SRT: 80-120 ms) and regular latency (SRT: >120 ms) (Fischer and Boch 1983;
Pare and Munoz 1996
). A summary for the two monkeys is
shown in Table 2. Monkey B did
not produce a bimodal distribution of prosaccadic SRTs and generated
very few correct prosaccades at express saccade latency. Both monkeys,
however, generated reflexive prosaccades in the antisaccade task (i.e.,
directional errors), which occurred at express saccade latency. These
were observed most often in the gap condition.
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Influence of stimulus eccentricity and direction
SACCADIC REACTION TIME.
Prosaccades were generated with shorter SRTs than antisaccades at all
stimulus eccentricities and directions tested (Fig. 3; P < 0.001). Likewise,
the gap condition consistently featured shorter SRTs than the overlap
condition for all stimulus locations in both the pro- and antitasks
(P < 0.001). Figure 3A shows the influence
of stimulus eccentricity on SRT with data collapsed across stimulus
direction. Mean SRTs were relatively large (mean SRT for all
conditions: 225 ± 6 ms) for stimuli at 2° eccentricity. As
eccentricity increased, mean SRTs decreased reaching a minimum at
810° eccentricity (mean SRT across both 8 and 10° for all conditions: 202 ± 5 ms). When stimulus eccentricity was increased further, mean SRTs began increasing reaching a mean SRT for all conditions of 227 ± 9 ms for stimuli at 16°. Therefore there
appeared to be an optimum eccentricity of ~8
10° where SRTs were
at a minimum. This trend was present in both pro- and antisaccade tasks
in both the gap and overlap conditions but was more prominent in the
overlap condition.
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DIRECTION ERRORS. Both monkeys made very few errors in the prosaccade tasks with the vast majority of direction errors occurring in the antisaccade trials. Furthermore the overlap condition featured significantly fewer direction errors compared with the gap condition (see Table 1).
Both monkeys had difficulty performing correct pro- and antisaccades to stimuli at 2° eccentricity (Fig. 4A; error rates for pro- and antisaccades: 7.7 and 17.9%, respectively). Performance improved when the stimulus eccentricity was increased to 4° (error rates: 0.8 and 4.5%, respectively). As eccentricity was increased beyond 4°, however, their performance steadily declined, reaching a maximum error rate of 3.8% for prosaccades and 36.3% for antisaccades for stimuli at 16° eccentricity. This trend was much more pronounced for antisaccades than for prosaccades (P < 0.05).
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SACCADIC GAIN. Stimulus location affected the gain of antisaccades significantly (Fig. 5; P < 0.01) but had little effect on the gain of prosaccades. Moreover, the state of fixation (i.e., gap vs. overlap condition) had no effect on the gain of both pro- and antisaccades.
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PEAK SACCADIC VELOCITY.
Both monkeys showed a significant interaction between stimulus
location and peak saccadic velocity for pro- and antisaccades whereas
the state of fixation (i.e., gap vs. overlap condition) had no effect
(Fig. 6). As stimulus eccentricity
increased, so too did peak saccadic velocity (Fig. 6A). Note
the rate of increase for prosaccades was much greater than for
antisaccades. Furthermore antisaccades, with the exception of stimuli
located at 2° eccentricity, had slower peak velocities compared with
prosaccades for all stimulus eccentricities tested. However, because
both animals made hypermetric antisaccades in response to small
stimulus eccentricities (see Fig. 5), the peak velocities for these
antisaccades were in fact slower than prosaccades of equal amplitude.
Thus these results show that for all amplitudes of saccades,
antisaccades were generated with lower peak saccade velocities than
prosaccades (see Fig. 6, C and D), consistent
with previous human (Smit et al. 1987) and monkey
(Amador et al. 1998
) studies. Stimulus direction showed no discernable pattern of influence on peak saccadic velocity with the
exception that prosaccades were faster than antisaccades across all
stimulus directions tested (Fig. 6B).
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DISCUSSION |
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The present study has shown that non-human primates can be trained
to generate both pro- and antisaccades to stimuli throughout the visual
field. We have also described the systematic effects of stimulus
eccentricity and direction on their behavioral characteristics. These
results from non-human primates follow very similar trends in terms of
metrics, kinematics, and reaction times to those observed in human
studies (Fischer and Weber 1992, 1997
; Goldring
and Fischer 1997
; Hallett 1978
; Smit et
al. 1987
; J. M. Dafoe, J. R. Broughton, I. T. Armstrong, and D. P. Munoz, unpublished data) and provide important supporting evidence for the use of this animal model in the
study of antisaccades.
Influence of stimulus location on saccade behavior
The location of the stimulus (i.e., stimulus eccentricity and
direction) had systematic and often significant effects on the behavioral characteristics of both pro- and antisaccades. Much of the
data suggested the presence of "preferred" stimulus locations that
optimized performance. For example, the relationship between SRT and
stimulus eccentricity revealed an optimal eccentricity of ~810°
where SRTs were at a minimum (Fig. 3A). A possible
contributing factor for the optimal amplitude of 8
10° may be
related to population coding of saccade metrics in the midbrain
superior colliculus (SC). Saccade-related neurons in the intermediate
layers of the SC are organized into a motor map coding the direction
and amplitude of contraversive saccades (Robinson 1972
).
Small amplitude saccades are represented more rostrally. Prior to the
execution of a saccade, a population of saccade-related neurons
(Lee et al. 1988
) spanning 1.5 mm of the SC are active
(Munoz and Wurtz 1995b
). The rostral SC also contains a
subset of neurons that discharge during visual fixation and small
amplitude, contraversive saccades ("fixation neurons")
(Krauzlis et al. 1997
; Munoz and Wurtz
1993
). It has been argued that there exists a continuum between
the saccade-related neurons and the fixation neurons across the motor
map of the SC (Munoz and Wurtz 1995b
). In addition,
anatomical studies have revealed stronger connections from the rostral
SC onto brain stem omnipause neurons (Buttner-Ennever et al.
1999
). Thus for small amplitude saccades, the rostral superior
colliculus may provide a conflicting signal composed of both fixation
and saccade commands that could take additional time to disambiguate,
resulting in longer latencies for smaller amplitude saccades. In fact,
it has already been argued that such a mechanism may account for the dead zone of express saccades, in which monkeys and humans are unable
to generate small amplitude (i.e., <2°) saccades at express saccade
latency (Weber et al. 1992
). Saccades of larger
amplitudes (i.e., >8
10°) should not experience this form of
interference. However, their latencies are still increased. This could
be due, in part, to a sensory perception factor. As the target
increases in eccentricity, its location on the retina moves away from
the fovea and progressively into an area of reduced visual acuity. Consequently the resulting sensory response, which will ultimately contribute to the activity necessary for driving a saccade, will be
diminished, leading to the pattern of increased latencies for larger
amplitude saccades shown in this and other studies (Kalesnykas and Hallett 1994
).
An examination of the relationship between stimulus direction and SRTs
reveals that in both the pro- and antisaccade tasks, SRTs were reduced
when saccades were directed toward the upper hemifield compared with
the lower hemifield (Fig. 3B). It is tempting to assume that
this may be due to potential overtraining with these locations.
However, this cannot account for the fact that similar trends have been
reported in other studies employing both non-human primates
(Boch et al. 1984) and humans (Fischer and Weber
1997
; Kalesnykas and Hallett 1994
; J. M. Dafoe, J. R. Broughton, I. T. Armstrong, and D. P. Munoz, unpublished data). The apparent bias toward certain stimulus
locations could, therefore represent a neurological bias in the actual
oculomotor system. For example, Thier and Andersen
(1996)
showed that the lateral intraparietal area (area LIP)
features a greater representation for the upper visual field than the
lower visual field. Consequently when Li and colleagues
(1999)
reversibly inactivated area LIP with muscimol, they
found that saccades to the upper hemifield were significantly more
impaired (i.e., hypometric with longer SRTs over controls) than those
to the lower hemifield. This adaptation could represent a type of
evolutionary and/or ecological inclination favoring quick orienting
movements toward certain locations over others in an effort to maximize
efficiency for specific behaviors. In support of this hypothesis,
Previc (1990)
argued that while the upper hemifield is
primarily associated with extra-personal space, the lower hemifield
deals more with peri-personal space. Optimizing movements to the upper
hemifield could confer an advantage with respect to scanning for food
or predators. Hemifield preferences in humans may also be influenced by
societal/cultural effects. Previous human studies have reported biases
in SRT and direction errors favoring the initiation of rightward
saccades compared with leftward saccades (Fischer and Weber
1997
; Fischer et al. 1997
; Munoz et al.
1998
; J. M. Dafoe, J. R. Broughton, I. T. Armstrong, and D. P. Munoz, unpublished results) This bias may be
due, in part, to differences associated with reading patterns (i.e.,
horizontal-left-to-right) (Abed 1991
) and would explain
the absence of this trend in animals.
If the oculomotor system is indeed optimized for generating saccades to certain locations, this would explain, in part, why the monkeys had particular difficulties in performing antisaccades to certain locations. Both monkeys had increased difficulties in generating antisaccades in response to stimuli located in the upper hemifield, thus requiring downward saccades. The production of an antisaccade requires the suppression of a reflexive prosaccade to the stimuli and the generation of a motor program to a "virtual" target. The increase in direction errors in the antisaccade tasks to stimuli in the upper hemifield (Fig. 4B) may be a result of greater difficulty in suppressing an "optimized" movement (i.e., saccade to the upper hemifield) in favor of generating a "nonoptimized" movement (i.e., saccade to the lower hemifield). Furthermore the correct downward antisaccades they did generate were more hypermetric relative to those generated to the upper hemifield (Fig. 5B). Therefore if the monkey is successful in suppressing the reflexive prosaccade, an antisaccade that he makes to the lower hemifield ("nonoptimized") would likely be less accurate than one generated to the upper hemifield ("optimized").
A final point to consider, with respect to a potential neurological
preference for certain saccade directions, relates to the finding that
memory-guided saccades to the upper hemifield tend to be hypermetric
whereas those to the lower hemifield are often hypometric (Gnadt
et al. 1991; White et al. 1994
), similar to the
pattern of dysmetria seen with antisaccades in this study. Why this
"upward drift" was present in memory-guided saccades and
antisaccades but not prosaccades may be due to the increased cognitive
requirements of these two tasks and consequently, involvement of higher
structures. Dias and Segraves (1999)
, for instance, showed that when the frontal eye fields (FEF) were inactivated with
muscimol, this upward drift was attenuated. This provides further
evidence that some of the directional biases/effects seen in this and
other studies may be due to influences from cortical structures related
to goals/target selection such as area LIP and the FEF and could
consequently represent an adaptation in behavioral strategies.
It is important to note that in addition to the factors outlined in the preceding text, another possible contributing factor to the dysmetria of antisaccade amplitudes (Fig. 5A) is that, during training, it is possible that the monkeys may have received additional training on stimulus locations between 5 and 10°, which may have biased performance.
State of fixation
Consistent with results from human studies (Boch and
Fischer 1986; Boch et al. 1984
; Fischer
and Boch 1983
; Fischer and Ramsperger 1984
;
Fischer et al. 1993
; Kalesnykas and Hallett
1987
), the monkeys in our study generated saccades with shorter
SRTs and a greater frequency of direction errors when stimuli were
presented in the gap condition compared with the overlap condition. In
contrast, the state of fixation appeared to have no effect on saccadic
gain or saccadic velocity. Introducing a gap between the disappearance of the FP and the appearance of a saccadic target has been shown to
increase preparatory activity in the paramedian pontine reticular formation (D. P. Munoz, M. C. Dorris, M. Pare, and S. Everling, unpublished observations), the SC (Dorris et al.
1997
; Munoz and Wurtz 1995a
) and the FEF
(Dias and Bruce 1994
; Everling and Munoz 2000
). In addition, fixation-related signals in the superior
colliculus are attenuated during gap conditions (Dorris and
Munoz 1995
). These changes in neuronal activity facilitate the
initiation of saccadic eye movements and are believed to be responsible
for the reduced SRTs seen in the gap condition (Dorris and Munoz
1995
, 1998
; Dorris et al. 1997
; D. P. Munoz, M. C. Dorris, M. Pare, and S. Everling, unpublished data).
Furthermore the presence of a gap period also facilitates the
occurrence of express saccades (see Fischer and Weber
1997
; Pare and Munoz 1996
for review). Express
antisaccades, however, were not generated by either monkey. In fact, no
study has ever presented evidence of correct antisaccades initiated at
express saccade latency. Although the gap condition reduces
fixation-related inhibition and increases preparatory activity, the
appearance of a stimulus produces a transient visual burst of activity
among saccade-related neurons in the superior colliculus contralateral
to the stimulus but ipsilateral to the movement direction on
an antisaccade trial (Everling et al. 1998a
). This
phasic visual burst coincides with reduced excitability of saccade-related neurons in the SC contralateral to the saccade direction therefore requiring additional time to generate a movement following this stimulus-related inhibition.
The increased error rates seen in the gap compared with the overlap
condition can also be accounted for by changes in excitability of
neurons in the SC and FEF. In the case of antisaccade trials, both
humans (Fischer and Weber 1997) and monkeys (current
study see Fig. 2) (Amador et al. 1998
) generate
reflexive prosaccades during antisaccade trials (i.e., direction
errors) at very short latencies, often in the range of express saccades
(80-120 ms), particularly when using the gap condition (Fischer
and Weber 1992
, 1997
). The reduction in fixation-related
inhibition and the reciprocal increase in preparatory activity that
occurs in the gap condition facilitates the generation of short-latency
saccades. Because the animals presumably know that within a block of
trials, the stimulus will appear at one of only two locations, there
will be an increase in preparatory activity among saccade-related
neurons coding for movements to either location (Everling and
Munoz 2000
; Everling et al. 1998a
, 1999
). Thus
when the eccentric stimulus appears after the gap period, if the
preparatory activity is high enough, the added stimulus-related phasic
visual burst can be enough to surpass a saccadic threshold and drive a
rapid, reflexive saccade to the stimulus.
The state of fixation had no effect on the gain or velocity of the
saccades. Based on the evidence discussed in the preceding text, it
would appear that SRT and the generation of a direction error are
highly correlated to preparatory activity as well as other neuronal
activity related to processing occurring prior to saccade initiation.
Saccadic gain and velocity, on the other hand, deal with the actual
execution of the saccade and are more dependent on the saccadic
generating circuit in the brain stem reticular formation which may not
be influenced by the state of fixation (Everling et al.
1998b; D. P. Munoz, M. C. Dorris, M. Pare, and S. Everling, unpublished data). It is, therefore possible that the neural
correlates of saccadic gain and velocity are not associated with motor
preparatory or fixation-related activity but other characteristics of
activity within saccade-related structures. However, in contrast,
Pratt (1998)
reported a difference in peak velocity of
prosaccades in humans in the gap and overlap conditions. A more
detailed analysis of the relationship between neural activity and
saccadic velocity may be required before any final conclusions can be made.
Non-human primates and antisaccades
One of the difficulties in using non-human primates as a model for the study of antisaccades is the uncertainty as to whether or not the animals understand the fundamentals of the task. Here we have employed a training regimen yielding consistent performance across three monkeys (2 providing data for this study and a 3rd animal that was subsequently trained for use in single-cell recording studies). These results are, for the most part, very consistent with the behavior observed in humans. After the completion of the training period, the monkeys were able to generate antisaccades to stimuli at all locations, indicating that they understood the task and were not simply generating saccades to locations of previous rewards. Moreover on occasions when the monkeys made a direction error to the stimulus during an antisaccade trial, they would often follow this up with a short-latency corrective saccade to the appropriate location despite not being rewarded for this behavior.
Another study that employed non-human primates to examine the
behavioral characteristics of antisaccades was performed by Amador and colleagues (1998). The paradigm used by these
authors had several important differences which resulted in predictable differences in behavioral measures. First, they used an immediate condition and a delayed condition for stimulus presentation in contrast
to our gap and overlap conditions. Successful completion of
memory-guided delayed tasks requires the suppression of reflexive saccades and consequently significantly alters SRTs (Gnadt and Andersen 1988
; Hikosaka and Wurtz 1983
). Both
monkeys in the Amador et al. (1998)
study had, on
average, longer SRTs than those in our study.
Second, one of the monkeys in the Amador et al. (1998)
study (MkA) featured shorter SRTs in the antisaccade tasks
compared with the prosaccade tasks, and SRTs for antisaccade direction errors were longer than correct antisaccades. These results are different from those obtained from a second monkey (MkD) as
well as what is reported in the human literature (Fischer and
Weber 1992
, 1997
; J. M. Dafoe, J. R. Broughton,
I. T. Armstrong, and D. P. Munoz, unpublished results).
Despite the fact that antisaccade SRTs were shorter than prosaccade
SRTs in monkey MkA, they were still in the range of not only
the antisaccade SRTs of the other monkey (MkD) but also the
monkeys used in our study, allowing for differences in the experimental
conditions. Thus it was performance on prosaccade trials that resulted
in the differences in the SRT trends. Therefore it is likely the
emphasis this particular monkey received during training on suppressing
reflexive movements and delaying saccades is responsible for the
increased SRTs for prosaccades (both correct prosaccades and incorrect antisaccades).
Despite the differences, these studies have both shown that it is possible to train primates to perform antisaccades revealing their suitability for neurophysiological studies into antisaccade generation. However, unlike humans who seem to automatically generate similar strategies to perform antisaccades, the method of training primates to perform antisaccades can have profound effects on how they complete the task. Consequently this can affect not only their behavior but may also have an effect on the neural correlates to this behavior. Therefore caution may be required in interpreting results from neurophysiological studies of primates and antisaccades to account for training effects.
Conclusions
The production of an antisaccade requires two functions: suppression of a reflexive prosaccade and the generation of a voluntary saccade to the opposite location in the absence of a guiding visual stimulus. The results from this study have shown that a monkey's ability to perform these two functions are affected by the location to where the saccade will be directed. We have also provided further evidence for a behavioral and neurological bias for certain saccade locations. Both pro- and antisaccades, directed toward the upper hemifield had short SRTs and were more accurate compared with those made to other locations. In addition, monkeys seem more likely to generate direction errors to those locations as opposed to other locations. The animals used in this study have shown similar trends to humans; this supports the use of monkeys to study the neural circuitry controlling the generation of antisaccades and translation of these findings to humans.
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ACKNOWLEDGMENTS |
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The authors thank A. Lablans, D. Hamburger, and K. Moore for technical expertise and I. T. Armstrong, B. D. Corneil, M. C. Davidson, and M. C. Dorris for commenting on earlier versions of the manuscript. D. P. Munoz is a research scholar of the ELJB Foundation and a Medical Research Council of Canada scientist.
This work was supported by a Medical Research Council of Canada Group Grant. A. H. Bell was supported by Queen's Graduate awards. S. Everling was supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft.
Present address of S. Everling: Dept. of Physiology, University of Western Ontario, London, Ontario, Canada.
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FOOTNOTES |
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Address for reprint requests: D. P. Munoz, Dept. of Physiology, Queen's University, Kingston, Ontario K7L 3N6, Canada (E-mail: doug{at}eyeml.queensu.ca).
Received 27 January 2000; accepted in final form 3 August 2000.
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