1Department of Medical Physics and Biophysics, University of Nijmegen, NL-6525 EZ Nijmegen; and 2Departments of Physiology and Anatomy, Erasmus University Rotterdam, NL-3000 DR Rotterdam, The Netherlands
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ABSTRACT |
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Goossens, H.H.L.M. and A. J. Van Opstal. Blink-Perturbed Saccades in Monkey. I. Behavioral Analysis. J. Neurophysiol. 83: 3411-3429, 2000. Saccadic eye movements are thought to be influenced by blinking through premotor interactions, but it is still unclear how. The present paper describes the properties of blink-associated eye movements and quantifies the effect of reflex blinks on the latencies, metrics, and kinematics of saccades in the monkey. In particular, it is examined to what extent the saccadic system accounts for blink-related perturbations of the saccade trajectory. Trigeminal reflex blinks were elicited near the onset of visually evoked saccades by means of air puffs directed on the eye. Reflex blinks were also evoked during a straight-ahead fixation task. Eye and eyelid movements were measured with the magnetic-induction technique. The data show that saccade latencies were reduced substantially when reflex blinks were evoked prior to the impending visual saccades as if these saccades were triggered by the blink. The evoked blinks also caused profound spatial-temporal perturbations of the saccades. Deflections of the saccade trajectory, usually upward, extended up to ~15°. Saccade peak velocities were reduced, and a two- to threefold increase in saccade duration was typically observed. In general, these perturbations were largely compensated in saccade mid-flight, despite the absence of visual feedback, yielding near-normal endpoint accuracies. Further analysis revealed that blink-perturbed saccades could not be described as a linear superposition of a pure blink-associated eye movement and an unperturbed saccade. When evoked during straight-ahead fixation, blinks were accompanied by initially upward and slightly abducting eye rotations of ~2-15°. Back and forth wiggles of the eye were frequently seen; but in many cases the return movement was incomplete. Rather than drifting back to its starting position, the eye then maintained its eccentric orbital position until a downward corrective saccade toward the fixation spot followed. Blink-associated eye movements were quite rapid, albeit slower than saccades, and the velocity-amplitude-duration characteristics of the initial excursions as well as the return movements were approximately linear. These data strongly support the idea that blinks interfere with the saccade premotor circuit, presumably upstream from the neural eye-position integrator. They also indicated that a neural mechanism, rather than passive elastic restoring forces within the oculomotor plant, underlies the compensatory behavior. The tight latency coupling between saccades and blinks is consistent with an inhibition of omnipause neurons by the blink system, suggesting that the observed changes in saccade kinematics arise elsewhere in the saccadic premotor system.
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INTRODUCTION |
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The oculomotor system and blinking evidently
interact. It is well known, for example, that blink-evoking stimuli
elicit a complex of motor actions that involve not only a transient
closure of the eyelids but also movements of the eye (e.g.,
Collewijn et al. 1985; Evinger et al.
1984
). Conversely, saccadic eye movements are frequently
accompanied by saccade-like movements of the upper eyelid
(Becker and Fuchs 1988
; Evinger et al.
1991
). Moreover, large saccades (Evinger et al.
1991
; Zee et al. 1983
) as well as combined
eye-head movements (Evinger et al. 1994
) tend to elicit concomitant blinks. It has been proposed that these so-called gaze-evoked blinks may result from a common premotor drive to the
saccadic and blink system (Evinger et al. 1994
). In
addition, there is neurophysiological evidence that several
saccade-related areas can modulate reflex blinks (see following text).
In the present study, we investigate how blinking affects the
generation of saccades in monkey. Although it is common knowledge that
blinking modifies saccades, quantitative data are scarce, and the
involved mechanisms are still unclear.
During a blink, a burst of activity occurs in the normally quiescent
lid-closing orbicularis oculi muscle while the tonic activity of the
lid-raising levator palpebrae muscle ceases in time-linked fashion (see
Evinger 1995 for review). Data from cat and rabbit
indicate that the eye rotations associated with blinks result from a
transient cocontraction of the extraocular muscles (Delgado-García et al. 1990
; Evinger and
Manning 1993
; Evinger et al. 1984
). As proposed
by Evinger and Manning (1993)
, this muscle-activation
pattern might result from a separate blink input to the extraocular
motoneurons (OMNs). If true also for primates, one may wonder how the
saccadic system accounts for blinking since it is generally assumed
that the programming and generation of spatially accurate saccades does
not rely on proprioception from the extraocular muscles (Guthrie
et al. 1983
). Instead, several reports have proposed that the
saccadic system combines retinotopic visual input with extraretinal
eye-position information, derived from an efference copy of the
oculomotor command, to accurately redirect the eyes (Guthrie et
al. 1983
; Hallett and Lightstone 1976
;
Sparks and Mays 1983
).
So far, experiments with human subjects indicate that saccade endpoints
remain quite accurate when goal-directed saccades are perturbed in
mid-flight by various blink-evoking stimuli (Becker 1993; Goossens and Van Opstal, unpublished observations;
Rottach et al. 1998
). As illustrated by Becker
(1993)
, supra-orbital nerve stimulation, for example, results
in briefly interrupted saccades that closely resemble those obtained
with electrical stimulation of the omnipause neuron (OPN) region in the
monkey brain stem (see e.g., Becker et al. 1981
;
Keller 1977
; King and Fuchs 1977
). Although the actual trajectory of the eye remained undisturbed in these
experiments (i.e., the eye only stops in mid-flight and then resumes
its original straight path), the latter data are generally considered
the best evidence that the saccade trajectory is controlled by error
feedback from efferent sources rather than by preprogrammed neural
signals that are computed prior to saccade initiation.
According to this so-called local feedback hypothesis, the brain stem
saccadic burst generator is controlled by an internal feedback circuit
that continuously compares a desired eye movement with an internal
representation (efference copy) of the actual movement until its goal
is attained (Jürgens et al. 1981; Robinson 1975
; Scudder 1988
; Van Gisbergen et al.
1981
). This concept is also used to explain how the saccadic
system can generate, in the absence of visual feedback, accurate
saccades of diminished velocity either due to pathology (Zee et
al. 1976
, 1983
) or to pharmacological manipulation
(Jürgens et al. 1981
). Thus local feedback is
presumed to make saccades more reliable and robust against errors.
Since saccadic gaze shifts tend to elicit blinks (Evinger et al.
1991
, 1994
; Zee et al. 1983
), it is conceivable that the saccadic system may also adequately deal with the effect of
blinks on its performance, possibly through local feedback.
Accumulating data indicate that the saccade and blink systems may
indeed interact at various premotor stages. Clinical studies have
shown, for example, that blinks can accelerate pathologically slowed
saccades (Zee et al. 1983) or initiate certain types of saccadic oscillations (Ashe et al. 1991
; Hain et
al. 1986
). Moreover patients with Huntington's disease often
blink to initiate voluntary saccades (Leigh et al.
1983
).
It is currently thought that the OPNs serve as a shared element of the
saccade and blink systems (Ashe et al. 1991;
Evinger et al. 1994
; Hain et al. 1986
;
Yee et al. 1994
; Zee et al. 1983
). OPNs
are located in the pontine nucleus raphe interpositus
(Büttner-Ennever et al. 1988
) and are known to
inhibit a variety of target neurons, including saccadic burst neurons
in the reticular formation of the pons. Consistent with the proposed
sharing of OPNs by the two systems, electrical microstimulation of the
OPNs yields interrupted saccades (Becker et al. 1981
;
Keller 1977
; King and Fuchs 1977
) and a
suppression of reflex blinks (Mays and Morrisse 1995
).
Moreover the tonic activity of OPNs has been shown to pause during
saccades as well as blinks (Cohen and Henn 1972
;
Fuchs et al. 1991
; Mays and Morrisse
1994
).
More recently, the midbrain superior colliculus (SC), which is known to
be critically involved in the generation of normal saccades, has also
been implicated in the interactions between blinks and saccadic gaze
shifts. For example, experiments in monkey (Gnadt et al.
1997) have shown that electrical microstimulation of the SC,
like in rats (Basso et al. 1996
), results in a transient suppression of air-puff-evoked trigeminal reflex blinks. Since the SC
is currently thought to inhibit OPN activity (Raybourn and
Keller 1977
), Gnadt et al. (1997)
reasoned that
this blink suppression is not directly mediated by the OPNs. Rather, as
in rodents (Basso and Evinger 1996
), the SC could
indirectly inhibit trigeminal blinks by activating the pontomedullary
nucleus raphe magnus, which tonically inhibits spinal trigeminal
neurons of the reflex blink circuit.
The purpose of the present paper is to explore, in detail, the effects
of blinking on the generation of saccades in monkey and to provide a
quantitative description of these interactions at the behavioral level.
We have focused on the influence of air-puff-evoked blinks on the
latencies, spatial trajectories and kinematics of two-dimensional
saccadic eye movements. We also examined the metrics and kinematics of
blink-associated eye movements to assess how these movements interfere
with saccades. To our knowledge, such data are not available in the
current literature. To further investigate interactions between the two
motor systems at the premotor level, the companion paper
(Goossens and Van Opstal 2000) describes the neural
activity patterns in the SC during blink-related saccade perturbations.
A preliminary account of part of these data has been presented
previously in abstract form (Goossens et al. 1996
).
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METHODS |
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Subjects and surgical procedures
Three adult male rhesus monkeys (Macaca mulatta; referred to as SA, PJ, and ER), weighing 8-9 kg, participated in the experiments. The animals had been trained to follow a small visual target with saccadic eye movements to obtain a small liquid reward. Records were kept of the monkeys' weight and health status and supplemental fruit and water were provided as needed. All surgical and experimental procedures were conducted in accordance with the European Communities Council Directive of November 24, 1986 (86/609/EEC) and were approved by the local university ethics committee.
The animals underwent three separate surgical sessions. Surgery was
performed under sterile conditions while the animal was under inhalant
anesthesia with N2O/O2 and
halothane. In the first session, a head holder was placed on the skull
by embedding eight titanium bone screws and four stainless-steel bolts
in dental cement. This head holder allowed for rigid and painless head
restraint during the experiments. In a second session, a thin
gold-plated copper ring (~18 mm diam) was implanted underneath the
conjunctiva of the left eye, following a method described by
Judge et al. (1980). This ring, which became firmly
attached to the eye by connective tissue, allowed for an accurate and
wireless recording of eye position (Bour et al. 1984
;
Ottes et al. 1986
; see also following text). Finally, a
recording chamber was placed over a trephine hole to allow for single
cell recordings in the superior colliculus that are described in the
companion paper (Goossens and Van Opstal 2000
).
Setup and experimental procedures
EXPERIMENTAL CONDITIONS.
All experiments were performed in a completely dark, sound-attenuated
room (dimensions, 3 × 3 × 3 m). The head-restrained monkeys were seated in a primate chair facing an array of 85 light-emitting diodes (LEDs) at polar coordinates R [0,
2, 5, 9, 14, 20, 27, 35] deg and
[0, 30, 60 ... 330] deg.
R is the eccentricity relative to the straight-ahead viewing
direction, which was parallel to the stereotaxic anterior-posterior
axis of the head.
= 0° corresponds to a rightward position
and
= 90° is upward. The LEDs (diameter, 0.2°; intensity,
0.2 cd · m
2) were mounted on a spherical wire
frame such that each LED was at a viewing distance of 85 cm.
AIR PUFFS. Trigeminal reflex blinks were evoked by brief air puffs on the left, recorded eye. These stimuli were generated by a pressure unit that was located outside the experimental room. In this way, the sound clicks produced by the air valve could not elicit an acoustic reflex blink. The air pulses (duration, 20 ms; intensity, 1.4-1.8 Bar at the source) were fed through a plastic tube (length, 4 m; diameter, 4 mm) that ended 1-2 cm in front of the eye. The fixed delay between triggering the pressure unit and the actual air puff on the eye was 43 ms. This was measured in vitro with a freely suspended search coil in front of the tube. The air-puff intensity was always well above threshold and, if necessary, adjusted during the course of an experiment (see Perturbation paradigm).
EYE AND EYELID POSITION RECORDING.
The two-dimensional (2-D) orientation (referred to as "position")
of the left eye was recorded with the double-magnetic induction technique developed in our laboratory (Bour et al. 1984;
Ottes et al. 1986
). The horizontal (40 kHz) and vertical
(30 kHz) oscillating magnetic fields that are required for this method
were generated by two orthogonal pairs of 3 × 3 m square
coils that were attached to the side walls, ceiling, and floor of the
room. The eye-position-dependent currents that are induced in the
implanted eye ring (see preceding text), were measured with a sensitive
pick-up coil that was placed directly in front of the eye before the
experiment. This coil signal was preamplified and demodulated into
horizontal and vertical DC eye-position components by two lock-in
amplifiers (PAR 128A). The resolution of this recording technique was
~0.2° in all directions.
DATA ACQUISITION AND STIMULUS PRESENTATION. Timing of the stimulus events as well as data acquisition were controlled by a PC-80486, equipped with a data-acquisition board (Metrabyte DAS16) and a digital I/O card (Data Translation 2817). Horizontal and vertical eye and eyelid position signals were amplified, low-pass filtered (150 Hz) and sampled with 12-bit resolution at a rate of 500 Hz per channel. Data acquisition started 400 ms prior to the offset of the initial fixation point and continued for 1.5 s. The raw data were stored on disk for off-line analysis (see Data analysis).
Behavioral paradigms
STANDARD PROTOCOL. At the beginning and end of each experiment, the monkey fixated 85 targets throughout the oculomotor range up to eccentricities of 35°. To that end, saccades were evoked from the straight-ahead LED to all peripheral LEDs (see EXPERIMENTAL CONDITIONS). In each trial, one of the LEDs was pseudo-randomly selected and presented for 900 ms immediately after the central fixation spot (800-1,600 ms presentation time) disappeared. The animal was rewarded after fixating the peripheral target for 300 ms. A trial was aborted when initial fixation was not maintained for the required period. The data obtained in these trial blocks were used for calibration of on-line and off-line eye-position signals (see Data analysis).
PERTURBATION PARADIGM. This paradigm was used to study the influence of blinking on visually evoked saccades. Three different trial types were randomly interleaved.
Control trials. The animal had to look at an initial fixation point that was presented for a variable period of 600-1,200 ms. As soon as the fixation point disappeared, either one of five peripheral targets (randomized) was flashed for 50 ms, and the monkey was required to refixate the remembered position of that target by making a saccade in complete darkness (see Fig. 1B). To receive a reward, the animal had to maintain initial fixation until 80 ms after the offset of the fixation spot, and the target position had to be acquired within ±4° and fixated for
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FIXATION PARADIGM. This paradigm was used to separately measure the rotations of the eye that accompany blinks as well as the latency of air-puff-evoked blinks. In each trial, the monkey had to fixate a straight-ahead LED for 1.5-2.0 s. The animal was rewarded for maintaining its gaze within a ±4° window throughout the demanded period. In 30% of the trials, referred to as fixation-blink trials, an air puff elicited a blink response (see Fig. 1A), and the monkey was always rewarded afterward. Trials with and without air puffs were randomly interleaved.
Data analysis
CALIBRATION OF EYE POSITION. Eye-position signals were calibrated off-line on the basis of 85 target fixations throughout the oculomotor range (±35°, see preceding text). Since we did not study the metrics and kinematics of the eyelid movements quantitatively, no attempts were made to calibrate these signals. Eyelid position signals are therefore presented in arbitrary units (au).
Because the double-magnetic induction method is characterized by smooth direction-dependent nonlinearities (Bour et al. 1984
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SACCADE AND BLINK DETECTION. Saccades were detected off-line on the basis of the calibrated eye-position signals by a computer program which applied separate velocity criteria for saccade onset (40°/s threshold) and offset (30°/s threshold). Any saccade recognition failures were corrected by the experimenter after visual inspection of the identifications made by the marking program. This was especially important in the case of perturbed saccades. Onsets and offsets of perturbed saccades were judged on the basis of position and velocity traces as well as on their two-dimensional trajectories that could be redisplayed as a real-time movement (see also RESULTS). To ensure unbiased detection criteria, no stimulus information was provided to the experimenter during saccade detection.
Blinks were detected separately with the same interactive computer program by using the raw vertical eyelid signals. Blink onsets could be readily detected on the basis of velocity and acceleration criteria since the initial eyelid movement during blinks is a very rapid downward movement (see RESULTS). Blink offsets were often poorly defined due to the low end velocity of the eyelid and were not used in the analysis. Blinks were easily dissociated from saccade-related eyelid movements because the former are characterized by a typical double-peaked velocity profile, whereas the latter are endowed with a roughly bell-shaped velocity profile (see e.g., Becker and Fuchs 1988SELECTION CRITERIA. Saccades with latencies <80 ms or >400 ms with respect to the onset of the peripheral target were excluded from the analysis. Successful control trials were those in which no spontaneous or gaze-evoked blinks occurred. Successful perturbation trials were those in which the air puff evoked a reflex blink in a time window that ranged from 50 ms before the onset of the saccade until 50 ms after its expected offset. The latter was derived from the mean duration of control saccades toward the same target. No time window was used to analyze latency interactions between saccades and blinks. Successful fixation-blink trials were those in which the air puff did not elicit a saccade or saccade-like eye movement. Apart from these three trial types, we also identified trials in which spontaneous blinks occurred, either during straight-ahead fixation or after a goal-directed response. Trials that were rejected as control trials because the saccade was accompanied by a gaze-evoked blink were also marked for separate inspection.
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RESULTS |
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The data presented in this paper were collected from three monkeys
during 32 experimental sessions (15, 12, and 5 sessions with
monkeys PJ, ER, and SA, respectively). In these
experiments, air-puff stimuli were used to elicit reflex blinks while
the animals were engaged in a saccade or a fixation task. In both
cases, the air puffs reliably evoked binocular reflex blinks with
latencies of 17.6 ± 4.5 ms (mean ± SD) (SA),
23.4 ± 6.2 ms (ER) and 20.2 ± 4.8 ms
(PJ), as derived from the onset of the contralateral lid
movement. Similar latencies were reported by Gnadt et al. (1997) for their rhesus monkeys. When evoked during
straight-ahead fixation (Fig. 1A), blinks were accompanied
by a transient, upward, and slightly abducting, rotation of the
recording eye (see also following text for further details).
Conversely, when the air puff was presented prior to the onset of an
impending visual saccade (Fig. 1C), the saccade and the
blink were initiated almost simultaneously as if the air puff triggered
both motor responses. One might argue that the eye-movement onset
reflects the blink-associated eye movement rather than the actual
saccade onset. Note, however, that early in the movement, size, and
shape of the horizontal eye-movement component are already different
from that in Fig. 1A, indicating that the eye-movement onset
and the actual saccade onset virtually coincide. As will be shown in
the following text by a model-based analysis (see Figs. 11 and 12), the
putative delay between the eye-movement onset and actual saccade onset
was estimated to be
6 ms.
To further illustrate this tight latency coupling, Fig. 1D
depicts the latency distribution of control saccades () and
perturbed saccades (
). The histograms clearly show that the latency
of saccades could be reduced by eliciting blinks. As may be observed, saccade latencies in control trials without air puffs (
) varied between 120 and 350 ms, which is typical for visually evoked saccades. By contrast, when air-puff stimuli were presented at a fixed moment near the expected saccade onset, the latencies of the eye movements were typically between 160 and 180 ms with respect to target onset (
), and occurred very shortly after the air puff arrived on the eye
(- - -). In this example, the mean saccade latency was 168 ± 14 ms as opposed to 216 ± 51 ms in the control condition
(t-test, P < 0.0001). A quantitatively
similar tight latency coupling between saccades and blinks was
reproducibly obtained with each monkey. Figure 1E depicts
the latency distribution of reflex blinks, during fixation-blink trials
(
) and during saccade perturbation trials (
), respectively. As
one may observe, there were no significant latency differences between
these two conditions.
Perturbation of saccades by blinks
As outlined in the INTRODUCTION, blinks are thought to interfere with saccade generation at several premotor levels. To gain further quantitative insight in the underlying interactions, we also examined the spatial trajectories and kinematics of blink-perturbed eye movements.
Figure 2 illustrates the results of a
typical perturbation experiment with monkey PJ. Figure 2,
A and B, compares a series of control saccades to
a series of representative perturbed saccades with concomitant
air-puff-evoked blinks. In the control condition (Fig. 2A),
the monkey made approximately straight saccades to the target, and the
bell-shaped velocity profiles () were typical for
20° saccades (see e.g., Van Opstal and Van Gisbergen
1987
). In Fig. 2B, an air-puff stimulus on the
recording eye evoked a blink reflex near the onset of the saccade. In
this condition, the 2-D saccade trajectories were substantially curved,
typically upward, and they were much more variable than in the control
condition. The kinematics of the eye movements were also strongly
affected: the peak velocity was substantially reduced, and the duration exceeded that of control responses by almost 150 ms. These effects can
be readily inferred from both the eye-position traces and the
multi-peaked velocity profiles. Despite these profound spatial-temporal perturbations, the saccades still ended close to the position of the
target even though all movements were made in complete darkness. Note
that it made no difference whether blinks were evoked near saccade
onset or in saccade mid-flight. One may also observe that the eye often
showed a clear reacceleration toward the target position. This is most
evident from the highlighted example (thick traces), in which the
initial change in eye position is immediately compensated by a
horizontal movement of the eye.
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Very similar features were consistently observed when the saccades in
control trials were accompanied by gaze-evoked blinks. As mentioned in
the INTRODUCTION, such blinks are saccade-related events
that tend to accompany large saccades (Evinger et al. 1991, 1994
; Zee et al. 1983
). To illustrate
qualitatively that the effects of blinking were not specific to the
applied perturbation paradigm, Fig. 3,
A and B, shows a series of saccades that were
perturbed by air-puff-evoked blinks and gaze-evoked blinks,
respectively (thin traces). The mean unperturbed control saccade
(R = 32 deg) is superimposed in both panels (thick
traces). Note that both types of blinks induced curved trajectories,
increased durations, and reduced peak velocities. In both cases, there
was also a clear goal-directed reacceleration of the eye after the
initial perturbation. In many sessions, however, the number of
gaze-evoked blinks was limited, depending on the amplitude of the
evoked saccades. Gaze-evoked blinks were virtually absent for saccades
20° or even
35° when the animal was well motivated. Larger
saccades (evoked from eccentric fixation points) were more frequently
accompanied by gaze-evoked blinks, but the resulting perturbations, in
general, were subtler than could be obtained with air-puff-evoked
blinks. We have not analyzed these differences in quantitative detail.
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Although blink-related perturbations were usually accounted for by the
oculomotor system, we noticed that a limited fraction of the perturbed
responses were not goal-directed. This bistable behavior is illustrated
in Fig. 4 for a session with monkey
PJ in which a relatively large number of such responses were
obtained. Figure 4A shows the 2-D trajectories of all
responses toward a target briefly presented at [R, ] = [60, 27] deg. Note that the perturbation was very poorly or not at
all compensated (
; ×, endpoints) in six responses, while eight
responses did show considerable compensation (· · ·;
endpoints). The scatter plot in Fig. 4B shows
the Cartesian endpoint errors relative to the target of all control
(
) and perturbed (
and ×) saccades evoked in this particular
experiment (pooled data of responses to 5 nearby targets). One may
notice that the endpoint errors were small in the far majority of
perturbed responses (
), while atypically large errors were obtained
in 10 perturbation trials (×; 24%).
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The overall impression gained from the data in Figs. 2-4 was that blink-perturbed eye movements remained fairly accurate despite severe perturbations in both the trajectory and the kinematics. To quantify this property further, we analyzed the endpoint accuracy of saccades that were perturbed by air-puff-evoked blinks in comparison with unperturbed control saccades. To that end, we measured the difference between the endpoints of perturbed saccades and the mean endpoint of control saccades toward the same target in two dimensions. The difference between these two response types, rather than the absolute accuracy, was analyzed because absolute accuracy may depend on many variables such as target duration and location as well as the subject's motivation.
Figure 5 illustrates the measures
that were used to quantify the 2-D accuracy of perturbed saccades as
well as the magnitude of the spatial trajectory perturbations. As
depicted in Fig. 5A, we measured the radial amplitude of
each perturbed saccade, Rp, and
computed the amplitude error, er, with
respect to the mean amplitude of corresponding control saccades,
c. Positive values of
er indicate that the perturbed saccade
was hypermetric with respect to the average control response. We
adopted this measure from Keller et al. (1996)
, who
recently used it to quantify the accuracy of OPN-interrupted saccades.
We also computed the difference between the endpoint of each perturbed
saccade and the mean endpoint of control movements in the direction
perpendicular to the mean control vector. Note that this
"orthogonal" error, indicated as ed in Fig. 5B, provides a
measure of how well the oculomotor system compensated for the changes
in eye position with respect to the normal saccade trajectory. These
trajectory perturbations, indicated as d in Fig.
5B, were quantified by measuring the maximum deviation from
the averaged trajectory of control saccades in the direction perpendicular to the mean control vector. Note that this measure is
independent from the saccade kinematics. The latter were quantified by
measuring duration and peak velocity of each saccade.
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Perturbed responses that were clearly not goal-directed (see Fig. 4) are not considered in this analysis because we believe they resulted from a different, atypical response mode (see DISCUSSION). To identify these responses, a computer algorithm detected the outliers in the endpoint distribution of perturbed saccades. In this way, eye movements with amplitudes and directions that differed by more than four standard deviations from the mean were excluded (e.g., the × data points in Fig. 4B). The fraction of nongoal directed responses ranged between 0 and 30% but was typically restricted to 10-15%. Corrective saccades that sometimes followed the initial perturbed response were also not included in this analysis.
Saccade metrics and kinematics
Figure 6, A and
B, compares the amplitudes of control and perturbed saccades
obtained in a series of experiments in all three monkeys. Saccades were
evoked by target displacements ranging between 9 and 60° in
monkeys PJ and ER and between 20 and 40° in
monkey SA. For each target eccentricity, data were selected from representative sessions in which the largest number of responses were obtained (n > 10, in both conditions). Figure
6A depicts the mean amplitudes and the standard deviations
of control saccades as a function of target eccentricity. The data show
that the monkeys typically made slightly hypometric saccades, which is
characteristic of visually evoked saccades. Figure 6B shows
similar data for perturbed saccades except that the amplitude is
expressed as an amplitude error relative to the mean amplitude of the
control saccades (er). Significant
differences between control and perturbed responses are indicated (*,
t-test, P < 0.025; otherwise
P > 0.1). It can be seen that the amplitude errors
were small (<3.0°) for target eccentricities 20°, while
hypometric responses were obtained for larger eccentricities (mean
errors up to
4.8°). Note, however, that the undershoots were
usually small compared with the saccade amplitude (up to ~10%),
particularly in monkey PJ. Moreover in all cases both the
trajectory and the kinematics of the eye movements were strongly
modified by the blink reflex (see e.g., Fig. 2). The effects on saccade
kinematics are quantified in Fig. 6, C and D
(same data sets as in A and B). One may observe
that the mean peak velocities of perturbed saccades (Fig.
6C;
,
,
,
) were reduced (t-test,
P < 0.0001) compared with those of control saccades
(
,
,
, - - -), often quite dramatically. One may further note that there were two- to threefold increases in the mean saccade duration (Fig. 6D; t-test, P < 0.0001). The standard deviations (error bars) also were much larger,
indicating a large variability in the duration of perturbed saccades.
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Further examination of the raw data suggested that the extent of compensation for the 2-D trajectory perturbations depended on the direction of the target jump. This directional dependence is illustrated in Fig. 7 by a worst-case example (monkey SA). Figure 7, A and B, compares large, perturbed saccades (thin trajectories) made to eccentric targets in two different directions. The mean control responses are also shown (thick trajectories). As may be observed, the change in movement direction was reasonably well accounted for when the saccades were made toward a target that was flashed near the horizontal meridian (Fig. 7A). By contrast, perturbed movements toward a target further down from the fixation point (Fig. 7B) not only fell short of the mean control response (and target) but also ended clearly above its endpoint. Note, however, that the eye movements were still directed toward the target location even though they started in a completely wrong direction (up and to the left).
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This property is further quantified in Fig. 7, C and
D, where the spatial trajectory perturbations as well as the
orthogonal endpoint errors of perturbed saccades are shown as a
function of target direction. Saccades were evoked to eccentric targets in various directions
[0, 30, ... 360] deg at either
R = 14° or R = 20° in monkeys
ER and PJ and at either R = 20° or
R = 27° in monkey SA. Since we noticed no
differences between leftward and rightward responses, target directions
are presented as angles relative to the horizontal meridian, where
+90° is upward and 0° is to the left/right. Figure 7C
depicts the mean and standard deviations of the trajectory
perturbations, d, for a series of representative sessions in
which the largest number of responses were obtained (n > 10, in both conditions). The data show that the largest
perturbations were obtained in oblique and horizontal directions. Note
that these perturbations could be quite large (up to ~15°) and that
they were endowed with a substantial variability (large standard
deviations). Although the trajectory perturbations were small for
vertical saccades, these findings do not imply that vertical saccades
were unaffected by blinks. Like horizontal and oblique saccades, their
kinematics were severely disturbed.
Figure 7D presents the mean and standard deviations of the orthogonal endpoint errors, ed, measured for the same perturbed saccades. Positive values indicate that the endpoints deviated in the same direction as the perturbation. The data show that the smallest errors were obtained for vertical target displacements, whereas systematically larger errors were found for horizontal and oblique-downward responses. Typically, these errors were much smaller than the amplitude of the trajectory perturbations (Fig. 7C; ed < d, t-test, P < 0.001). Yet the errors were typically positive, which indicates that there were systematic deviations of the saccade endpoints in the direction of the perturbation (*, t-test, P < 0.025; otherwise P > 0.1). Hence it appeared that the movements compensated for deviations from the normal trajectory, albeit not equally well for all target directions tested. No significant compensation (P > 0.1) was obtained in only one experiment with monkey ER for target displacements in the 30° downward direction.
Blink-associated eye movements
The data presented in the preceding text indicate that the oculomotor system compensates, at least partly, for large blink-related perturbations in both direction and velocity. These results are consistent with the idea that a dynamic feedback circuit may control the saccade trajectory (see INTRODUCTION), but they do not exclude alternative possibilities. For example, a transient blink-related signal, in principal, could be added to the saccadic command at the level of the OMNs, and the resulting perturbation could be restored entirely by passive elastic forces within the oculomotor plant. To obtain more insight into the possible mechanisms underlying the observed perturbations, we examined the eye movements accompanying blinks in more detail.
Figure 8 depicts a series of eye movements associated with air-puff-evoked reflex blinks in the fixation paradigm while the monkey (ER) attempted to fixate a straight-ahead fixation spot. The examples in Fig. 8, A and B, illustrate the two types of blink-associated eye movements that were reproducibly obtained in all three animals. As shown in Fig. 8A, the 2-D trajectories of blink-associated eye movement often described approximately closed loops, meaning that the eye returned to its initial position in a single movement. Note that there was considerable variability in these movements. Yet the largest excursions of the eye were consistently upward and slightly abducting. By examining also the eye movements during spontaneous blinks, we noticed that the direction and size of the loops depended on the initial eye position. This feature is illustrated in Fig. 9, which shows the 2-D trajectories of a series of eye movements that accompanied spontaneous blinks. Note, for example, that when the animal (PJ) was looking to the left, blinks resulted in a rightward initial eye rotation, while downward movements were obtained when the animal was looking upward. During straight-ahead viewing, spontaneous blinks were accompanied by eye movements that were initially upward and slightly abducting as was obtained also for air-puff-evoked responses.
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This behavior, together with the increase in endpoint errors (Figs. 6 and 7), raised the question whether the observed compensation could have resulted entirely from passive restoring forces within the oculomotor plant. This would occur, for example, if a blink was associated with a transient activation of the OMNs through a pathway that bypasses the local feedback circuit.
Interestingly, however, it appeared that the end position of the eye
after a blink-associated eye movement was often clearly different from
its initial position. This is illustrated in Fig. 8B, which
depicts blink-associated eye movements evoked by air-puff stimuli in
the same trial block as those shown in Fig. 8A. After such
"truncated" eye movements, a downward corrective saccade toward the
fixation spot frequently followed. The latencies of these corrective
saccades (measured relative to the offset of the blink-associated eye
movement) typically fell within the normal range of visually guided
saccades, although strikingly short latencies (down to 20 ms) were
observed as well. In Fig. 8B, for example, the shortest
latency was 64 ms. One may also note that during this latency period,
the eye remained stationary at its eccentric orbital position. Since
the latter requires a tonic activation of extraocular muscles to
prevent low-velocity drift (Robinson 1975), these data
hint at an involvement of the neural eye-position integrator (see also
DISCUSSION). In this respect, it is also of interest to
note that the downward return movements of the eye in Fig.
8A were fairly rapid (i.e., peak velocities ~200°/s) and
did not follow a slow exponential time course. The latter feature is
typical for the passive return movements of the eye that follow
electrical microstimulation of the trochlear nerve or abducens nucleus
(Sparks and Mays 1983
; Sparks et al.
1987
).
To further quantify the nature of blink-associated eye movements, we
also analyzed their kinematics by dividing the movements into two
subsequent phases: the (upward) eye excursion phase and the (downward)
eye return phase (see Collewijn et al. 1985, for a
similar analysis on blink-associated eye movements in humans). Figure
10, A-D, illustrates the
results of this analysis which included eye movements associated with
air-puff-evoked blinks (
) and spontaneous blinks (
). All
responses were obtained in the straight-ahead fixation task (pooled
data from 8 sessions with monkey PJ). Figure 10,
A and B, shows the velocity-amplitude-duration relations for the eye excursion movements. Figure 10, C and
D, shows these relations for the eye return movements. Note
that peak velocity as well as duration were approximately proportional to the amplitude of the movement. Table 1
lists the regression results of two monkeys (ER and
PJ). Note also that the data obtained under spontaneous and
air-puff-evoked blinking conditions overlap considerably. The average
peak velocity for a 9-10° excursion movement was ~250°/s and
~200°/s for a return movement of similar amplitude. Thus the peak
velocity of return movements was only ~20% lower than for excursion
movements, whereas one would have expected a considerable difference if
the return movements were passive. For example, assuming a plant time
constant of T = 250 ms, an entirely passive 10°
return movement would have had a peak velocity of only 40°/s. For
comparison, Fig. 10, E and F, shows the
velocity-amplitude-duration relations for (downward) corrective saccades that followed blink-associated eye movements (note the factor
2 scale difference with Fig. 10, A-D). One may readily
observe that saccades have higher peak velocities and shorter durations and that they are more stereotyped.
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Taken together, these findings suggest that the rapid return phase of blink-associated eye movements is under neural control rather than the mere result of elastic restoring forces within the oculomotor plant (see also DISCUSSION).
Superposition of two eye movements?
When electrical microstimulation was applied to the OMNs just
before the onset of a visually evoked saccade, no active compensation for the stimulation-induced eye displacement was observed
(Sparks and Mays 1983; Sparks et al.
1987
). Rather, the eye movements could be well described by a
linear superposition of the passive movements that occur after
stimulation and the control saccade. Although the data in Figs. 8 and
10 suggest that the observed compensatory behavior in the case of
blink-perturbed saccades does not result from passive restoring forces,
the results so far do not exclude the possibility that blink-associated
and saccadic eye-movement commands are independent and executed
entirely in parallel. That is, compensation could be an intrinsic
property of the blink system rather than the saccadic system.
This possibility was further examined in two ways. First, the average unperturbed control saccade was subtracted from perturbed saccades toward the same target to reconstruct the putative independent perturbation signal. In the case of a linear superposition of two separate commands at the motoneuron level, the reconstructed eye movements should be very similar for saccades of different amplitude and closely resemble those of pure blink-associated eye movements measured in isolation. Alternatively, to reconstruct the putative independent saccade signal, the average blink-associated eye movement in response to air-puff stimulation alone was subtracted from perturbed saccades. In the case of linear superposition, the reconstructed eye movements should closely resemble the unperturbed control saccades, both in their trajectories and kinematics. Note that the requirements should be met in both reconstructions if linear superposition is to be upheld.
Figure 11 shows illustrative examples
of both analysis procedures. Figure 11, A and D,
depicts a series of perturbed saccades toward two targets at different
eccentricities (thin traces; R = 20° and
R = 9°, respectively). The mean control responses to these targets are also indicated (thick traces). Figure 11,
B and E, shows the reconstructed movements (thin
traces) that were obtained by subtracting control from perturbed
saccades (data aligned with eye-movement onset). Shown are the 2-D
difference trajectories as well as the eye-position (H
and
V) and eye-velocity (
) difference signals as function of time (thin traces). For comparison, the average blink-associated eye movement (returning type; see Fig.
8A) in response to air-puff stimulation alone is
superimposed (thick traces). Note that the reconstructed perturbations
are not only different from the average blink-associated eye movement but also different for the two data sets (obtained in the same trial
block). The latter is most evident from the 2-D trajectories. In both
cases, the reconstructed trajectories formed approximately closed
loops, which is indicative for full compensation, but the shape and
orientation of these loops is clearly different. These features
persisted when the perturbed and unperturbed responses were delayed
with respect to each other rather than aligned to their onsets. Hence
it appeared that blink-perturbed eye movements could not be described
by linear addition of an unperturbed saccade and a pure
blink-associated eye movement. Figure 11, C and
F, shows the alternative procedure, applied to the same data
sets, in which the reconstructed movements (thin traces) were obtained
by subtracting the average blink-associated eye movement (returning
type; see Fig. 8A) from the perturbed saccades (data aligned
with eye-movement onset). For comparison, the mean unperturbed control
saccades are replotted in these panels (thick traces). As expected from the data in Fig. 11, B and E, the reconstructed
saccades are clearly different from mean control saccade in that their
position and velocity profiles are quite different for both data sets.
Interestingly, however, it appeared that the reconstructed 2-D
trajectories were more or less straight (albeit not for all responses
toward the target at [R,
] = [9, 150] deg). Very
similar results were obtained also for monkey PJ. For
monkey SA, we obtained insufficient blink-associated eye
movements of the returning type to compute a reliable average. Obviously, the reconstruction results in Fig. 11, C and
F, were different when blink-associated eye movements of the
truncated type (see Fig. 8B) were subtracted from the
perturbed saccades.
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Another feature that may be derived from the reconstruction data in Fig. 11, C and F, is that the delay between the eye-movement onset and the onset of the reconstructed saccades is very short. This is further detailed in Fig. 12, which shows the initial velocity profiles of reconstructed saccades that were derived from responses toward targets at three different eccentricities (9, 14, and 20°). To exclude mid-flight perturbed responses, data were averaged over a series of trials (n > 20) in which the onset of the contralateral blink lid movement preceded the eye-movement onset. Note that there is a rapid increase in velocity starting within the first 10 ms after eye-movement onset. Note also that the three traces already diverge after ~6 ms, indicating that even the early movements are part of the goal-directed response.
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DISCUSSION |
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The data presented in this paper show, for the first time, various aspects of monkey saccadic behavior that are affected by trigeminal reflex blinks. In summary, air-puff-evoked blinks had a strong influence on the latency as well as on the kinematics and spatial trajectories of visually evoked saccades. Near the onset of a blink, the ongoing movement direction of the eye was considerably modified, resulting in substantial deviations from the normal, approximately straight, saccade trajectory. These perturbed saccades often had a diminished peak velocity, and a two- to threefold increase in their duration was typically observed. Despite the strong disruptive nature of blinks, the animals could still generate quite accurate eye movements, as the perturbations were largely compensated. These compensations occurred in mid-flight, i.e., well before the eye movement ended, and did not rely on visual feedback since they were completed in total darkness.
In what follows, an attempt is made to identify the mechanisms that could underlie this complex oculomotor behavior. To that end, we will discuss the following issues: are the eye movements induced by blinks partly passive in nature (i.e., does the return phase of the blink-associated eye movements result from plant mechanics) or are they entirely due to a neural control signal and where in the neural circuitry do blink-related signals interfere with saccade generation? The latter point touches on the central concept in saccade models that a local feedback loop controls the saccade trajectory. It is also related to the question about the existence of a separate neural pathway generating blink-associated eye movements.
Direction of blink-associated eye rotations
There is some controversy in the literature about the direction of
eye movements associated with blinks (see Evinger et al. 1984, for review). Measurements with search coils in human
subjects (e.g., Collewijn 1985
; Evinger et al.
1984
; Goossens and Van Opstal, unpublished observations),
and recently also in monkeys (Gnadt et al. 1997
), have
indicated that a transient downward and adductive rotation of the eye
often accompanies blinks. In the experiments reported in the present
paper, the largest eye excursions were typically upward and slightly
abducting (Fig. 8). These results cannot be ascribed to an artifact of
the double-magnetic induction technique (see METHODS) for
the following reasons: first, this method allows for a wireless
recording of eye orientation, preventing a potential obstruction of
natural eye movements by wire leads in the orbit. Second, when
blink-associated eye movements ended at an eccentric orbital position
that was above the horizontal meridian, it was consistently observed
that this eye position was maintained for a prolonged period of time
until the animal generated a voluntary downward corrective saccade
toward the fixation spot (Fig. 8B). Both features readily
indicate that the preceding blink-associated eye movements were truly upward.
Note, however, that the actual eye-movement direction during blinks has
been mentioned to depend on the initial eye position (e.g.,
Evinger 1995). Indeed, an eye-position dependence was
also noticed (but not illustrated) by Gnadt et al.
(1997)
for their monkeys. Although not systematically
investigated in the present study, we have qualitatively confirmed and
illustrated such an eye-position effect on blink-associated eye
movements in monkey (Fig. 9). Similar findings have been previously
reported in cats (Gruart et al. 1993
) and, more
recently, also in humans (Bour et al. 1999
). We
therefore believe that differences in the actual "straight-ahead"
eye position relative to the head (poorly specified in previous
studies) may better account for the apparent discrepancy in movement
directions, than differences in recording techniques.
Latency coupling
The present experiments show that saccades and blinks are
initiated almost simultaneously when an air-puff stimulus arrives just
prior to an impending visual saccade (Fig. 1). A similar facilitation
of saccade initiation by blinks has been previously observed in several
clinical studies (Leigh et al. 1983; Zee et al.
1983
), and also a reduction of head-movement latencies has been
reported for healthy subjects (Evinger et al. 1994
).
Although a short latency difference of ~6 ms between eye-movement onset and (putative) saccade onset emerged from our model-based analysis (Fig. 12), this apparent latency difference could be artificial. This may be understood by realizing that when saccade- and blink-related eye movements are superimposed (not necessarily linear), the net eye velocity will exceed the onset detection threshold (see METHODS) earlier for perturbed eye movements than for pure blink-associated eye movements. As a result, the subtraction method tends to overestimate the delay between eye-movement onset and saccade onset. The exact delay, however, is not readily deduced from the data. Presumably, it is <6 ms, if not zero. Given these uncertainties, we believe it is parsimonious to consider the eye-movement onsets as the most reliable, model-free estimate of the actual saccade onsets (Fig. 1).
The tight latency coupling reported in this paper readily supports the
idea also that the neural pathways that are involved in the initiation
of saccades and blinks are tightly coupled. As reviewed in the
INTRODUCTION, the OPNs are thought to embody this linkage.
Several investigators have reported, for example, that the tonic
activity of OPNs pauses during saccades as well as during blinks
(Cohen and Henn 1972; Fuchs et al. 1991
;
Mays and Morrisse 1994
). Thus when a blink is evoked
just prior to a saccade, one would expect that the concomitant pause in
OPN discharge results in the immediate initiation of the impending saccade due to the disinhibition of the saccadic burst generator.
Peripheral mechanisms?
Besides the clear modification of saccade latencies, blinking also
had a substantial influence on the kinematics and on the spatial
trajectories of visually evoked saccades (Fig. 2). A near-complete compensation for these saccade perturbations ensured, however, that the
eye still landed close to the extinguished target (Figs. 2 and 4).
Evinger and Manning (1993) reported that, except for the
superior oblique, all extraocular muscles of the rabbit are coactivated
during blinks. Since such activation pattern is not observed during
other types of oculomotor behavior, they proposed that rabbit OMNs
receive a blink-related input that is independent of their eye-movement
inputs. Thus one could suspect that the eye-movement responses obtained
in the present study resulted merely from a addition of independent
blink-related and saccade-related motor commands at the motoneuron level.
To test for this simple hypothesis, we have performed the analysis
outlined in Fig. 11. Under the implicit assumptions that the
blink-associated eye movement and the saccade start approximately simultaneously and that the mechanical properties of the oculomotor plant remain unaltered during saccade-blink responses, the conclusion of this analysis is that a simple linear addition of two independent motor commands cannot account for the observed behavior. Similar findings were recently reported for horizontal saccades in humans (Rottach et al. 1998). The first assumption is readily
supported by the data in Fig. 12 that indicate a latency difference of
~6 ms, or less, between the eye-movement onset and the saccade onset.
The second assumption, however, merits some additional comments. In the event of extraocular muscle cocontraction, a concomitant change in the mechanical properties of the plant (as an increase of the overall plant stiffness) is also expected. It is interesting to consider the consequences of such a change. It is generally accepted that the brain stem saccade generator is organized in such a way that, under normal conditions, the pulse and step signals on the oculomotoneurons exactly cancel the plant dynamics. In other words, the overall transfer function of the brain stem-plant system equals unity. As a result, a burst signal proportional to eye velocity will yield a normometric saccade (i.e., neither undershoots nor overshoots; see Fig. 13, bottom right).
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Suppose that the plant stiffness transiently increases because of a
blink-related cocontraction, say from k to k'.
The plant time constant is then consequently lowered to T' = r/k' (with r the plant viscosity). The overall
transfer function of the brain stem-plant system is then given by
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Clearly, this effect cannot be "repaired" by a simple gain modulation at the level of the brain stem burst generator. Thus under the increased stiffness condition, the eye is expected to systematically undershoot the target by a relative fraction that is given by T'/T = k/k'. The data indicate, however, that the actually observed undershoots were typically small (see e.g., Figs. 2 and 4) and hardly dependent on the saccade amplitude (Fig. 6). We conclude therefore that the increase in plant stiffness, if present, is probably limited to a few percent. Consequently, the saccadic system may assume that under blinking conditions the plant has not changed and that the internal brainstem model of the plant need not be updated dynamically.
Separate blink-related oculomotor signals?
One may then wonder about the nature of the signals that underlie the complex eye-movement trajectories. An important first question is whether the eye movements associated with blinks actually result from separate blink-related inputs to the OMNs.
In cats and rabbits, trigeminal terminals on abducens motoneurons have
been described (Baker et al. 1980; Cegavske et
al. 1997
). Similar findings have been reported regarding visual
inputs involved in flash-evoked reflex blinks (Holstege et al.
1986
). It appears, however, that only a limited percentage
(10-15%) of cat abducens motoneurons exhibit a burst discharge after
air-puff, supraorbital nerve, and flash stimulation and that this
fairly weak burst of activity lags the onset of orbicularis oculi
motoneuron activity 10 ms (Delgado-García et al.
1990
; Trigo et al. 1999
). In rabbits, the
activation of extraocular muscles also lagged the onset of orbicularis
oculi muscle activity, leading Evinger and Manning
(1993)
to suggest that extraocular motoneurons and facial
motoneurons receive different afferent inputs. According to these
investigators, the most likely source of blink-related input to rabbit
OMNs could be the supraoculomotor region.
To our knowledge, it is still unknown whether such blink-related inputs
to the OMNs exist in monkey. Unlike many other animals, primates do not
have a retractor bulbi muscle, which, for example, in cat and rabbit,
pulls the eye back into the orbit during blinks. Instead monkeys only
have a small accessory lateral rectus muscle, which presumably evolved
from the retractor bulbi system (Spencer et al. 1981).
Because of these species-specific differences, the existence of
separate blink-related inputs in primates is not clear.
In cat, it has been found that lid movements during
spontaneous, flash-, tone-, and air-puff-evoked blinks exhibit
different kinematics, suggesting a distinct elaboration in their
respective sensory pathways (Domingo et al. 1997). Our
present data, on the other hand, show that the kinematics of eye
movements associated with spontaneous and air-puff-evoked blinks
overlapped considerably (Fig. 10). This suggests that in monkey, these
two types of eye movements are generated by a common
pathway, rather than by blink-related signals of different origin
converging onto the OMNs. We also noticed that blink-associated eye
movements were often "truncated," yielding a substantial net eye
rotation. Such responses were not followed by eye-position drift but
rather by a corrective saccade (Fig. 8B). Similar results
have been reported also by Takagi et al. (1992)
for
human subjects. These features are difficult to reconcile with the idea
that separate blink-related signals would act directly on the OMNs. In
that case, one would expect that the return phase of blink-associated
eye movements are merely a secondary, passive effect of cocontraction
of the extraocular muscles. Yet the kinematics of the return movements
further demonstrate that they too are under neural control (Fig. 10).
Whether or not separate blink-related signals act directly on the OMNs remains difficult to decide on the basis of behavioral data only. Yet the present results clearly show that such a signal does not simply add to a normal saccade. Moreover, subtraction of pure blink-associated eye movements from perturbed saccades yielded saccade reconstructions with altered kinematics compared with control saccades (Fig. 11, C and F). We conclude therefore that the blink system interferes to a considerable degree with the process of saccade generation at a premotor level that is upstream from the extraocular motoneurons.
Premotor interactions
Several findings in the present study support the idea that the eye movements associated with blinks could result from interactions within the oculomotor system itself:
First, we noticed that the initial change in eye position during blink-perturbed saccades was immediately followed by a reacceleration of the eye toward the target location. This reacceleration usually occurred in a direction quite different from the overall direction of the control saccade (see Figs. 2, thick trace, and 3 for illustrative examples). This adequate adjustment of the movement direction strongly suggests that the compensatory responses were based on accurate information about the actual changes in eye position. When it is assumed that these changes in eye position were due to a transient blink-related signal acting downstream from the local feedback loop of the saccadic system (e.g., at the OMNs), such compensatory behavior is not readily expected.
Second, both the metrics and kinematics of blink-associated eye
movements (Figs. 8 and 10) indicate that these movements are entirely
under neural control rather than that the return phase results merely
from passive elastic restoring forces within the oculomotor plant. In
particular, the absence of an eye-position dependent drift after a
truncated blink-associated eye movement (Fig. 8B) strongly
suggests that the neural eye-position integrator, which subserves the
generation of the step component of saccades (see e.g., Fig. 13), is
involved. The latter would occur, for instance, when blink-associated
eye movements would result from direct activation of the saccadic burst
cells (since these cells provide direct input to the integrator) rather
than from independent excitation of OMNs by a separate blink-related
signal. Cohen and Henn (1972) indeed reported that a
subset of saccadic burst neurons in the monkey paramedian pontine
reticular formation (PPRF), which are recruited for rapid horizontal
eye movements, also discharge during spontaneous blinks, irrespective
of whether the associated eye movements are horizontal. Interestingly,
a blink-related excitation of saccadic burst cells, in combination with
OPN inhibition, would also provide an explanation for the occurrence of
blink-induced saccadic oscillations (Hain et al. 1986
).
Finally, blinks induced considerable changes in the saccade kinematics
(Fig. 6), even after subtraction of pure blink-associated eye movements
(Fig. 11, C and F). Several investigators (e.g., Becker 1993; Zee et al. 1983
) have
suggested that such changes might arise from an indirect influence of
blinking on the saccadic burst generator through a modulation of the
OPN discharge. The present results are indeed consistent with the idea
that blinking affects the OPNs but, as discussed in the preceding text,
the observed latency coupling between saccades and blinks can best be
explained by an inhibition of the tonic OPN discharge. By
contrast, to account for the measured reduction in saccade velocity
(Fig. 6) by means of an OPN mechanism, one would have to assume an
excitation of the OPNs. Since recording studies also
indicate that the OPNs pause during blinks (Cohen and Henn
1972
; Fuchs et al. 1991
; Mays and
Morrisse 1994
), we propose that a change in OPN discharge does
not underlie the changes in saccade kinematics observed in the present
experiments. Possible effects due to cocontraction of the extraocular
muscles cannot readily account for the changes in the saccade
kinematics either (see preceding discussion).
Apart from the OPNs, the intermediate and deep layers of the SC also
provide major input to the brain stem saccade generator (see e.g.,
Moschovakis and Highstein 1994; Sparks and
Hartwich-Young 1989
for review). As was outlined in the
INTRODUCTION, recent studies indicate that the midbrain SC
is involved in the interactions between saccades and blinks
(Basso and Evinger 1996
; Basso et al.
1996
; Gnadt et al. 1997
). It is therefore
conceivable that the observed changes in saccade kinematics may
originate, at least partly, from changes in SC activity. Experimental
support for this possibility will be provided in detail in the
companion paper (Goossens and Van Opstal 2000
), which
describes the activity patterns of saccade-related neurons in the SC
during blink-perturbed saccades.
Accuracy of error compensation
In a minority of trials, typically no more than 15%, no
compensation for the disturbance occurred (Fig. 4). It is difficult to
provide a convincing explanation for these cases only on the basis of
behavioral data. Possibly, the response was prematurely aborted in
these trials (e.g., like blinks in the fixation paradigm; see Fig.
8B) due to processes that also abolished the initial saccade
program. Neurophysiological evidence for this hypothesis will be
provided in the companion paper (Goossens and Van Opstal 2000). In the majority of severely perturbed responses,
however, a near-complete compensation for the saccade disturbance
ensured that the eye landed close to the extinguished target (Figs.
2-4). The accuracy of the error corrections did not depend much on
saccade amplitude (Fig. 6), although a slight dependence of final
accuracy on saccade direction was observed (Fig. 7). We have no simple explanation for the latter phenomenon.
It is important to realize that all movements were executed under entirely open-loop conditions, i.e., in the absence of any visual feedback. In the previous sections, we have argued that the full sequence of movement events in the perturbation trials may be due to neural control rather than to plant mechanics and that the neural signals interact at premotor stages within the saccadic system. If true, the present compensation data provide strong additional support for the existence of a local feedback loop that is thought to control the instantaneous saccade trajectory.
Previous saccade-interruption paradigms [intrasaccadic stimulation of
either the OPNs (Keller and Edelman 1994) or of the rostral SC (Munoz et al. 1996
)] have so far only
halted the saccade in mid-flight without disrupting the
movement direction. In addition, electrical microstimulation
may inadvertently excite adjacent oculomotor pathways (running both
upstream and downstream), which makes the interpretation of stimulation
data less obvious than at first glance. Indeed, OPN stimulation also
transiently stops the saccade-related burst in the intermediate layers
of the SC, possibly through a retrograde activation of rostral SC cells
(Keller and Edelman 1994
).
In contrast to electrical microstimulation, the blink-perturbation paradigm leads to a natural, noninvasive disturbance of the 2-D saccade trajectory as well as to considerable changes in both saccade kinematics and timing. The paradigm consistently affects all three major stages believed to underlie the saccade: the programming of the movement vector, the initiation of the saccade, and its actual execution. Although the interpretation of the results in terms of local feedback mechanisms is far from trivial and still not settled (see discussion in previous sections), we believe that this paradigm may provide a valuable tool to further investigate this issue.
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ACKNOWLEDGMENTS |
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We thank H. Kleijnen and T. van Dreumel for technical support. The staff of the central animal facility is acknowledged for providing excellent care for our monkeys. Dr. F. van der Werf is thanked for helpful discussions, and both anonymous referees are acknowledged for constructive criticism, which greatly improved the paper.
This research was supported by the Dutch Foundation for the Life Sciences (SLW, project 805-01.072; H.H.L.M. Goossens), the University of Nijmegen (A. J. Van Opstal), and the Human Frontiers Science Program (A. J. Van Opstal, RG0174/1998-B).
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FOOTNOTES |
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Address for reprint requests: H.H.L.M. Goossens, Dept. of Medical Physics and Biophysics, University of Nijmegen, Geert Grooteplein 21, NL-6525 EZ Nijmegen, The Netherlands.
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 26 March 1999; accepted in final form 16 February 2000.
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REFERENCES |
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