Department of Cell and Developmental Biology and the Program in Neuroscience, SUNY Upstate Medical University, Syracuse, New York 13210
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ABSTRACT |
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Tu, Tyson A. and E. Gregory Keating. Electrical Stimulation of the Frontal Eye Field in a Monkey Produces Combined Eye and Head Movements. J. Neurophysiol. 84: 1103-1106, 2000. The frontal eye field (FEF), an area in the primate frontal lobe, has long been considered important for the production of eye movements. Past studies have evoked saccade-like movements from the FEF using electrical stimulation in animals that were not allowed to move their heads. Using electrical stimulation in two monkeys that were free to move their heads, we have found that the FEF produces gaze shifts that are composed of both eye and head movements. Repeated stimulation at a site evoked gaze shifts of roughly constant amplitude. However, that gaze shift could be accomplished with varied amounts of head and eye movements, depending on their (head and eye) respective starting positions. This evidence suggests that the FEF controls visually orienting movements using both eye and head rotations rather than just shifting the eyes as previously thought.
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INTRODUCTION |
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While the frontal
eye field (FEF) has been classically viewed as an eye movement area,
recent studies in eye-head coordination of gaze movements have caused a
surge of interest in how oculomotor areas (such as the FEF) may control
head as well as eye movements. In some early frontal lobe experiments
(Ferrier 1874; Rasmussen and Penfield
1947
), stimulation of parts of the frontal cortex (including
the FEF) was found to produce both contralateral eye and head
movements, but these studies lacked well-defined stimulation parameters
and provided little data regarding the metrics of these movements.
Later stimulation studies were done more systematically, with better
description of the eye movements produced by stimulation of the FEF
(Bruce et al. 1985
; Robinson and Fuchs
1969
). However, these experiments were performed on animals
that had their heads restrained (head fixed), restricting the ability
of the FEF to produce a coordinated eye and head movement.
Recent studies regarding gaze orientation (combined use of eye and head
movements) in the superior colliculus and other brain stem areas
(Cowie and Robinson 1994; Freedman et al.
1996
) have prompted us to look at the possibility that the
frontal eye fields are responsible for controlling both eye and head
movements when attempting to fixate gaze on a target. Previous work in
our lab has shown that ablation of the cortex along both banks
of the arcuate sulcus (encompassing both saccadic and smooth eye
movement areas of the FEF) produces deficits in both eye and head
components of saccades and pursuit movements (Keating et al.
1997
). In the present study, we electrically stimulated the FEF
using parameters similar to those used to produce fixed-vector eye
movements (Bruce et al. 1985
; Tehovnik and Sommer
1997
) in head-fixed animals, but we allowed the monkeys freedom
to rotate their heads ±45° along the horizontal axis (head free).
Results showed that evoked movements in these animals were composed of
both head and eye components that summed toward the total gaze shift.
Some of these data have appeared in abstract form (Tu and
Keating 1998
).
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METHODS |
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Two male rhesus monkeys (Macaca mulatta) were each
equipped with two search coils during aseptic surgeries using general
anesthesia (isoflourane). One coil was implanted in the eye
(Judge et al. 1980) to measure gaze position, and one
fixed on the head holder (offset from the axis of horizontal rotation
by 2 cm) for horizontal head position, with eye position calculated
from measured gaze and head positions. Following a period of behavioral
training (see following text), recording chambers were implanted first over the left FEF and then the right FEF, and stimulation (biphasic pulses in 50- to 400-ms trains of 25-300 µA, 250 Hz, 0.25-ms pulse duration) was performed using stainless steel or tungsten
microelectrodes. Exploration and data collection for stimulation sites
in the head-free animal were normally performed with currents of
100-200 µA and train durations of 200 ms (these numbers were arrived
at after experimenting with higher and lower currents and durations to establish best range for eliciting reliable head movements). FEF sites
were identified by eliciting reliable fixed-vector (similar amplitude
and direction regardless of starting position) gaze movements. In many
cases, these sites were confirmed to be in the low-threshold FEF
(Bruce et al. 1985
) by stimulation with 25- to 50-µA
pulses. Experimental measurements in the head-free condition were often
made using stimulation with higher currents of 200 µA [using the
equation i = kr2 and k = 1,292 µA/mm2 (Stoney et al.
1968
), current spread at 200 µA can be estimated to be
~0.39 mm].
The monkeys were trained to orient to visual targets in a darkened room that were back-projected onto a screen with different colored spots of light guiding the head and eyes. Head position was controlled by requiring the monkey to visually guide its head movements to a target (red 0.25° diam spot) using an onscreen cursor (4 white dots in a square 2° to a side) that moved in direct correspondence to its head movements. Eye/gaze fixations were directed to a white target spot that was 0.3° in diameter. Head movements were either completely restricted by the head post (head-fixed condition) or were restricted to ±45° of yaw from center, with limited freedom (<15°) along the pitch or roll axes (head free condition). The torso in one monkey was stabilized by self-fastening plastic straps (Velcro) that held the monkey's arms to the chair, keeping body rotations to a minimum. Torso movements that were observed in the other animal were minimal (this subject usually sat with its torso facing center, with occasional shifts to no more than 15° away from center) even with full 45° head movements.
Given that we wanted the subjects to orient to different head and gaze starting position, trials began with a period during which the animals fixated a head position target using the head tracking cursor (Fig. 1A). Once the head target was fixated, the eye/gaze target was flashed on the screen for one second to constrain initial eye/gaze position (Fig. 1B), after which all visual information (head target, head cursor, and eye target) was extinguished, and stimulation began 70 ms (monkey TM) or 100 ms (monkey PN) later (Fig. 1C; see Fig. 1D for gaze, eye, and head traces). Head and eye targets were separated by either 15° (1 target at center and 1 target at either ±15°) or 20° (both targets at opposite ±10° from center). This behavioral paradigm allowed us to control both head and eye starting positions (monkey PN could maintain at least a 15° head-eye separation at the time of stimulation, although there was a tendency for the head to drift toward the gaze fixation point as can be seen in Fig. 1D). However, it was particularly difficult for monkey TM to maintain divergent eye and head positions, therefore a second paradigm was adopted for this subject in which no eye/gaze targets were used and only initial head position was required (see Fig. 1E). Control trials (50% of trials) for both procedures were run in the same manner but without the application of current, thus allowing the subject to make completely spontaneous movements in the dark. The monkey was rewarded with juice for maintaining initial fixation on either head and eye or head fixation points.
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Gaze and head positions were directly monitored via the search coils, and eye position was calculated by subtracting head from gaze position. Saccades from stimulation trials were considered to be evoked by stimulation based on latency (within 100 ms of stimulation) and gaze direction (contralateral to side of stimulation) criteria. For trials containing evoked saccades, gaze and eye amplitude (starting position subtracted from final position) were measured at time of peak displacement, and head amplitude was taken as head position at time of maximum gaze amplitude. Trials with double-stepped or staircase saccades were not used in analysis as there were no discernible breaks in head movement from which to determine the head amplitude from the first saccade. Trials in which saccades occurred immediately preceding (within 100 ms) the start of stimulation were also discarded due to continued movements of the head or eyes during this period. In control trials, the first saccade following the blanking of visual targets was used as an example of a spontaneous saccade for comparison to electrically evoked saccades.
All experimental and surgical procedures were approved by the Committee for Humane Use of Animals in our institution and followed the National Institutes of Health guidelines regarding the care and use of laboratory animals.
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RESULTS |
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Active stimulation sites were found in both frontal eye fields (Fig. 2A) of monkey TM and the left FEF of the monkey PN. The sites from monkey TM were identified as lying largely within the upper limb of the arcuate sulcus. Explorations in more ventral areas of the prearcuate gyrus did not elicit any saccadic responses or had current thresholds too high to consider as valid sites. Sites that evoked largely vertical gaze responses were also not considered in this study as the monkeys had limited freedom of head movement along the vertical axes. Stimulation sites were found between 1.0 and 7.0 mm below the surface of the dura, and many penetration tracks yielded multiple stimulation locations along their depths.
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Of 124 electrode penetrations explored (in both monkeys), 45 penetrations yielded a total of 98 sites from which we could elicit eye
or gaze movements. Of these, 51 sites produced large horizontal gaze
movements that included a head component (see Fig. 2, B and
C, for example of 1 such site). In monkey PN, 14 other sites were found that either produced head movements in the
absence of any gaze movements [i.e., fully compensated by the
vestibuloocular reflex (VOR)] or had gaze movements that were initiated by head movements (with initial VOR) that were then followed
(within 60 ms) by eye movements (both conditions could be observed
during stimulation of a single site). Stimulation of these sites during
a head-fixed condition was able to produce eye movements that resembled
the fixed vector movements normally elicited by stimulation of the FEF.
Additionally, in monkey PN we found four sites from which we
were able to elicit smooth eye movements (SEM) similar to those found
by others (Gottlieb et al. 1993). These sites were
located more ventral and deeper in cortex than the saccade related
sites. The remaining 29 sites produced gaze movements that were too
small or were oriented more vertically and so did not contain a
head component.
All evoked eye and head movements (i.e., components of gaze shift) were
toward the side contralateral to stimulation with large variations in
gaze direction and amplitude between sites. Most saccades were directed
toward the upper two quadrants (there were very few downward directed
saccades in the sites we stimulated), with more vertical saccades
producing little or no horizontal head movement. Saccades that
exhibited larger horizontal gaze shifts were more likely to produce
consistent and larger head movements. Using currents of 200 µA and
train durations of 200 ms, we found sites with gaze amplitudes of
70° (from a contralateral gaze starting position) with head
contributions approaching 25°. At lower currents or train durations,
head contributions decreased in size, while total gaze amplitudes
stayed relatively constant (data to be presented in a later report).
Head contributions at a single site decreased toward zero when
horizontal gaze amplitudes approached 15-20° (Fig.
3A).
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Initial positions of eye, head, and gaze had an influence on their
respective evoked movement amplitudes (Fig. 3, B-D). In general, for gaze and its separate eye and head components, an initial
position in the hemifield opposite to the direction of movement caused
a larger evoked movement than a starting position toward the side of
movement. This relationship was observed for all movements, though the
eye and head components exhibited a stronger position effect than the
overall gaze movements (with data from 20 sites, average slope ± SE of initial position vs. movement amplitude was found to be
0.457 ± 0.069 for eye,
0.165 ± 0.024 for head, and
0.080 ± 0.020 for gaze).
To distinguish evoked from spontaneous movements, half of all trials were run without electrical stimulation, and these data were compared with the stimulation data. Eye and head movements were each found to have very different latency and amplitude distributions during the stimulation and the control trials, with control trials showing a much wider distribution of movements and latencies. Mean stimulated eye/gaze latency was 47.0 ± 2.4 ms (n = 72) versus 152.2 ± 21.1 ms (n = 83) for controls; mean stimulated head latency was 58.3 ± 5.3 (n = 59) ms versus 171.6 ± 21.1 ms (n = 83) for controls. Mean stimulated gaze amplitude was 21.82 ± 0.39° (n = 77) versus 8.36 ± 1.59° (n = 83) for controls; mean stimulated head amplitude was 4.28 ± 0.39° (n = 77) versus 0.80 ± 0.55° (n = 83) for controls (P < 0.001 for all comparisons).
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DISCUSSION |
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There have been earlier hints from stimulation experiments that
the FEF is involved with both head and eye movement control in both
primates/humans (Ferrier 1874; Rasmussen and
Penfield 1947
) and cats (Guitton and Mandl
1978
). Lesion data from head-free monkeys has also shown
that the FEF is part of the system for coordination of head and eye
movements (Van der Steen et al. 1986
). Recent work from
our lab found that FEF lesioned animals (the lesion included the
posterior bank of arcuate sulcus) had significant deficits in movement
amplitude toward the side contralateral to the most recent surgery.
Even though the monkeys displayed different strategies for compensating
for these deficits, they all exhibited a prolonged deficit for either
head or eye movements (Keating et al. 1997
).
In this study, we have shown that stimulation of the low threshold and
other areas of FEF studied in earlier experiments (Bruce et al.
1985; Robinson and Fuchs 1969
) produce not only
eye movements but a gaze movement composed of both eye and head
components. The head and eye movements we observed were all directed
contralateral to the side of stimulation but were seen to be affected
by starting position. Given that the gaze shifts we evoked were still
approximately `fixed vector` (i.e., were not as affected by starting
position), this suggests that the FEF is producing a gaze vector signal
rather than two separate eye and head signals. More work is needed to clarify this point, however, and further work is also being done to
clarify the effects of stimulation intensity, duration, and location on
the relative contributions of eye and head to evoked gaze movements.
Thus far, our head-movement results bear a strong resemblance to
those found in the superior colliculus (SC) (Freedman et al.
1996). This should not be surprising considering the seemingly parallel functioning of the two areas and the discovery of increasingly complex interactions (via reciprocal connections) between them (Lynch et al. 1994
; Segraves and Goldberg
1987
; Sommer and Wurtz 1998
). The latencies we
have recorded for both gaze and head shifts put the FEF firmly upstream
from the SC, but it would be interesting to measure the gaze responses
to FEF stimulation in the absence of the SC, given the direct
connections of the FEF to oculomotor centers in the brain stem.
To conclude, these results show that the FEF can control at least one other component of the gaze movement system (in this case the head, although body/torso movements may also play a role), rather than solely controlling the eyes, as previously thought. It remains to establish whether the FEF controls the eyes and head separately or if its output is in the form of a gaze signal as our results suggest. For the time being, however, the idea of a purely eye-movement-oriented FEF can no longer be supported.
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ACKNOWLEDGMENTS |
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We are grateful for the technical support of G. Rygiel.
This research was supported by National Science Foundation Grant IBN9807787 and the SUNY Research Fund.
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FOOTNOTES |
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Address for reprint requests: T. A. Tu, Dept. of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210 (E-mail: tut{at}mail.upstate.edu).
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 18 January 2000; accepted in final form 2 May 2000.
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REFERENCES |
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