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. II. Superior Colliculus Activity. J. Neurophysiol. 83: 3430-3452, 2000. Trigeminal reflex blinks evoked near the onset of a saccade cause profound spatial-temporal perturbations of the saccade that are typically compensated in mid-flight. This paper investigates the influence of reflex blinks on the discharge properties of saccade-related burst neurons (SRBNs) in intermediate and deep layers of the monkey superior colliculus (SC). Twenty-nine SRBNs, recorded in three monkeys, were tested in the blink-perturbation paradigm. We report that the air puff stimuli, used to elicit blinks, resulted in a short-latency (~10 ms) transient suppression of saccade-related SRBN activity. Shortly after this suppression (within 10-30 ms), all neurons resumed their activity, and their burst discharge then continued until the perturbed saccade ended near the extinguished target. This was found regardless whether the compensatory movement was into the cell's movement field or not. In the limited number of trials where no compensation occurred, the neurons typically stopped firing well before the end of the eye movement. Several aspects of the saccade-related activity could be further quantified for 25 SRBNs. It appeared that 1) the increase in duration of the high-frequency burst was well correlated with the (two- to threefold) increase in duration of the perturbed movement. 2) The number of spikes in the burst for control and perturbed saccades was quite similar. On average, the number of spikes increased only 14%, whereas the mean firing rate in the burst decreased by 52%. 3) An identical number of spikes were obtained between control and perturbed responses when burst and postsaccadic activity were both included in the spike count. 4) The decrease of the mean firing rate in the burst was well correlated with the decrease in the velocity of perturbed saccades. 5) Monotonic relations between instantaneous firing rate and dynamic motor error were obtained for control responses but not for perturbed responses. And 6) the high-frequency burst of SRBNs with short-lead and long-lead presaccadic activity (also referred to as burst and buildup neurons, respectively) showed very similar features. Our findings show that blinking interacts with the saccade premotor system already at the level of the SC. The data also indicate that a neural mechanism, rather than passive elastic restoring forces within the oculomotor plant, underlies the compensation for blink-related perturbations. We propose that these interactions occur downstream from the motor SC and that the latter may encode the desired displacement vector of the eyes by sending an approximately fixed number of spikes to the brainstem saccadic burst generator.
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INTRODUCTION |
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In the companion paper (Goossens and Van
Opstal 2000), we reported that blinking affects various aspects
of saccadic behavior in monkey. It appeared that air-puff-evoked blinks
had a considerable influence on both the kinematics and the spatial
trajectories of saccadic eye movements. When elicited before saccade
onset, these reflex blinks also reduced the saccade latencies
substantially. Despite the strong disruptive nature of the evoked
blinks, visually elicited saccades remained quite accurate in the
absence of visual feedback. These behavioral data support the idea that
blinking interferes with the saccadic premotor system and that an
active control system may compensate for the blink-related
perturbations. The neural mechanisms underlying these saccade-blink
interactions, however, have so far received little attention in the
literature and are difficult to assess on the basis of behavioral data alone.
Up to now, neurophysiological experiments have shown that the tonic
activity of brain stem omnipause neurons (OPNs) pauses during blinks as
well as saccades (Cohen and Henn 1972; Fuchs et
al. 1991
; Mays and Morrisse 1994
), thereby
disinhibiting saccadic burst neurons in the pontomedullary brain stem.
These findings suggest that OPNs mediate, at least partly, the tight
latency coupling between saccades and blinks. However, as discussed in the companion paper (Goossens and Van Opstal 2000
) and
in view of current models of saccade generation, the changes in both
the trajectory and the kinematics of blink-perturbed saccades cannot be
simply ascribed to an interaction at this premotor level. Moreover, a
linear superposition of saccade- and blink-related signals at the
extraocular motoneurons cannot readily account for the observed saccade
behavior either. It is conceivable therefore that blinking affects
other premotor stages of the saccadic system as well.
Recent studies indeed hint at the possibility that also the midbrain
superior colliculus (SC) could be an important site of saccade-blink
interactions. For example, both in rats (Basso et al.
1996) and in monkeys (Gnadt et al. 1997
), it has
been observed that electrical microstimulation of the SC transiently
reduces the magnitude of air-puff-evoked blinks. As in rats
(Basso and Evinger 1996
), the monkey SC presumably
excites a nonsaccadic pathway that inhibits the reflex blink circuitry
(Gnadt et al. 1997
). However, it is still unknown
whether blinking affects the discharge patterns of saccade-related
collicular neurons and how this could in turn affect saccade
generation. In the present paper, we therefore studied single-unit
activity in the intermediate and deep layers of the SC with the use of
the blink-perturbation paradigm.
It is well established that the SC has extensive projections to
saccadic burst cells in the pontomedullary brain stem and that the SC
is critically involved in the generation of normal saccadic eye
movements (see e.g., Moschovakis and Highstein 1994; Sparks and Hartwich-Young 1989
for reviews). Many
neurons in its intermediate and deep layers generate a burst of
activity just before and during saccades directed to a particular
region of the visual field, referred to as the movement field of the
neuron. Together, these saccade-related burst neurons (SRBNs) form a
topographically organized motor map in which anatomically nearby cells
have overlapping movement fields (Lee et al. 1988
;
Mays and Sparks 1980
; McIlwain 1982
;
Ottes et al. 1986
; Robinson 1972
;
Schiller and Stryker 1972
).
Until recently, it was generally held that the amplitude (R)
and direction () of an impending saccade is specified by the location of the active cell population in the SC motor map
rather than by the temporal discharge patterns of the
recruited neurons. Several studies have suggested, however, that the
collicular output may also determine the kinematics and trajectory of
the saccade (Berthoz et al. 1986
; Lee et al.
1988
; Munoz et al. 1991
; Van Opstal et
al. 1990
; Waitzman et al. 1991
; Wurtz and
Optican 1994
). These findings have led to new quantitative
models that place the SC inside the so-called local feedback loop. This
internal feedback circuit is thought to control the saccade trajectory by a continuous comparison of the desired eye displacement signal with
an internal representation (efference copy) of the actual eye
displacement during the saccade (e.g., Arai et al. 1994
;
Droulez and Berthoz 1991
; Lefèvre and
Galiana 1992
; Optican 1995
; Van Opstal and Kappen 1993
). Previously most models assumed that
the local feedback loop is closed through assemblies of cells in the pontomedullary brain stem (Jürgens et al. 1981
;
Scudder 1988
; Van Gisbergen et al. 1981
).
A difficulty in studying the role of the SC in the control of saccades
is the stereotyped relationship between the amplitude of normal
saccades and their duration and peak velocity (referred to as the
"main sequence") (Bahill et al. 1975; Fuchs
1967
). In an attempt to overcome this problem, previous
saccade-interruption paradigms have used intrasaccadic microstimulation
of either the OPNs (Keller and Edelman 1994
) or of the
rostral SC (Munoz et al. 1996
). In these experiments, it
was found that the microstimulation not only stopped the eye in saccade
mid-flight, but it also induced a brief pause in the discharge of
collicular SRBNs. Shortly after the stimulation ended, the saccade
resumed its course, and the same population of SC cells that was active
before the stimulation was reactivated even though the resumed movement
did not belong to the movement field of these cells. By contrast no, or
only minimal, activity was found in cells whose movement field optimum matched the metrics of the resumed saccades. By what mechanism the same
neurons are reactivated is still unclear. One possible explanation is
local feedback, which indeed predicts a resumed discharge (e.g.,
Arai et al. 1994
). The finding that the SRBN discharge
rate during the resumed saccades still showed the same monotonic
relation with the remaining motor error than the one obtained for
uninterrupted saccades further supported this hypothesis (e.g.,
Das et al. 1995
).
However, a problem that still hampers the interpretation of the saccade-interruption data are the stereotyped kinematics of the resumed movements and the lack of a change in eye-movement direction. Moreover, the potential danger of stimulating adjacent oculomotor pathways, both upstream and downstream from the SC, makes the interpretation of stimulation data less obvious then at first glance. For example, OPN and rostral SC stimulation not only stopped the saccade in mid-flight, but it also interrupted the SRBN discharge. Hence it appeared that the SRBNs did not represent the remaining motor error during the interruption period. It is unclear, however, whether the cessation of SRBN discharge could be a side effect of the electric stimulation. It is ambiguous therefore whether the SRBNs detected the perturbation (through feedback) or whether they instead caused the interruption of the saccade. By imposing natural perturbations on the saccadic system that affect both the kinematics and spatial trajectories of saccadic eye movements, the blink-perturbation paradigm may offer an opportunity to circumvent these difficulties.
In view of current models of the SC and the notion of local feedback
control, the present paper investigates how blink-related spatial-temporal perturbations of the saccade trajectory are reflected in the SC activity patterns. A preliminary account of these experiments has been presented in abstract form (Goossens et al.
1996; Van Opstal and Goossens 1999
).
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METHODS |
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Subjects
The neurophysiological data presented in this paper were
obtained from three rhesus monkeys (Macaca mulatta) and were
collected during the behavioral experiments described in the companion
paper (Goossens and Van Opstal 2000). Details about the
setup, surgical procedures, and methods used to measure eye and eyelid
position as well as the applied behavioral paradigms, are described in that paper. Here we provide only a brief summary, and additional methods that were used to record and analyze the single-cell activity. All experiments 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.
Apparatus
The head-restrained monkeys were seated in a primate chair
facing an array of 85 light-emitting diodes (LEDs) in an otherwise completely dark room. The horizontal and vertical components of the
left eye position were measured with the double-magnetic-induction technique (Bour et al. 1984). Movements of the
contralateral right eyelid were measured with the magnetic search-coil
induction technique (Collewijn et al. 1975
) by taping a
small coil on the eyelid. Air puffs (20 ms, 1.4-1.8 Bar) were
generated by a pressure unit and presented on the recording eye to
elicit trigeminal blink reflexes.
The activity of single units was recorded with glass-coated tungsten
microelectrodes (0.2-1.2 M) that were positioned in the SC using a
hydraulic stepping motor (Trent Wells). The latter was mounted on the
stainless steel recording chamber that was placed above a trephine hole
at stereotaxic coordinates [AP, RL] = [0,0] and aimed at the SC.
The electrode signal was amplified (Bak Electronics, Model A-1),
low-pass filtered (15 kHz), and monitored on an oscilloscope. Action
potentials were detected by a level detector and discriminated on the
basis of their waveforms using a real-time decomposition of the first
four principal components (e.g., Epping and Eggermont
1987
). The accepted spike events were subsequently fed into a
four-bit spike counter, which produced a stepwise DC output that was
sampled at a rate of 1 kHz. This ensured that no spikes were missed,
irrespective of the instantaneous discharge rate during vigorous bursts
of action potentials.
SC localization and histology
The in vivo localization of the SC was based on the following
criteria: 1) the stereotaxic coordinates of the recording
sites corresponded closely to the coordinates of the SC as given by Snider and Lee (1961). The size of the area with visual-
and saccade-related activity was also in accordance with this atlas.
2) A region without action potentials, corresponding to the
superior cistern, was often passed before the electrode entered the
superficial layers of the SC. Usually the upper boundary of the SC was
readily recognized by the activity of visual neurons with limited
contralateral receptive fields and response latencies of ~70 ms.
3) At deeper locations, typically between ~0.8 and 3 mm
below the SC surface, clear saccade-related activity was encountered.
In these layers, electrical stimulation with pulse trains (25 negative
pulses of 0.5-ms duration at 500 Hz) at low current strengths (20-50
µA) evoked reproducible saccades that corresponded well
with the movement fields of nearby saccade-related neurons. The
latencies of stimulation-evoked saccades were ~20 ms, and thresholds
for evoking saccades were typically <10 µA. 4)
The topographic motor map of the SC (Robinson 1972
)
could reliably account for the optimal saccade vector of cells
encountered in subsequent penetrations. And 5) after further
lowering of the electrode, sustained auditory-evoked responses with
short latencies, indicative for the inferior colliculus, were often
encountered (Goossens et al. 1997
).
After completing the experiments, two of the monkeys (SA and ER) were deeply anesthetized with an overdose of pentobarbital and perfused directly through the internal carotid artery with 2 l phosphate-buffered saline, pH 7.4, at 37°C, followed by 2 l of fixative containing phosphate-buffered 2% paraformaldehyde and 2.5% glutaraldehyde, pH 7.4. Immediately after perfusion, the midbrain was dissected out. Serial cryostat sections were made and prepared for standard histology (Nissl staining). Examination of the midbrain sections at low and high magnification showed that the penetrations were made through the SC. Most of the penetrations reached the intermediate and deep layers.
Experimental protocol
After isolating an SRBN, saccades were evoked toward all LEDs of
the target array. These data were used for accurate calibration of the
eye-position signals (see Goossens and Van Opstal 2000) and to estimate the location and extent of the cell's response field.
Subsequently, the movement field of the neuron was characterized in
detail by eliciting saccades to a series of targets presented inside
and neighboring the cell's response field.
A typical movement field scan consisted of 85 different
fixation/target configurations: 5 different target positions and 17 different initial fixation positions (usually within 5° from the center LED), yielding a spatial resolution down to 0.5°. In each trial, the monkey first looked a fixation spot that was presented for
800-1,600 ms (randomized). Then as soon as the fixation spot disappeared, a peripheral target was presented for another 900 ms at a
pseudo-randomly selected location that the animal refixated with a
saccade. When a better dissociation between visual- and saccade-related
activity was required, the saccade latencies were increased by
presenting the target 100 ms prior to the offset of the fixation point
(overlap paradigm) (Fischer and Weber 1993).
After this standard procedure, which was usually repeated near the end
of a recording session, the neuron's activity was tested with the use
of the blink-perturbation paradigm that has been described
in the companion paper (Goossens and Van Opstal 2000). In short, saccades were made in complete darkness from a fixation point
to either one of five randomly selected and briefly flashed (50 ms)
peripheral targets, typically into the central region of the cell's
movement field. In 30% of the trials, air puffs were presented at a
fixed moment after target onset (between 120 and 180 ms) to elicit a
reflex blink (mean latency ~20 ms) near the onset of the saccade.
Control and perturbation trials were randomly interleaved with catch
trials. In the latter trials, target positions were chosen such that
the evoked saccades could be matched to the successive eye-movement
components of perturbed responses (see RESULTS, Fig. 11).
Cells were also tested with the use of the fixation-blink
paradigm, in which air-puff-evoked blinks were elicited while the
animal attempted to fixate a straight-ahead fixation spot (see
Goossens and Van Opstal 2000
).
Data analysis
For details regarding saccade and blink detection procedures as
well as statistic criteria that were used to discriminate between
compensatory and noncompensatory responses, the reader is referred to
METHODS and RESULTS of the companion paper
(Goossens and Van Opstal 2000).
The raw single-cell activity was displayed in spike rasters aligned on
specific events such as target onset, air puff onset, the onset or
offset of a saccade, or the onset of a blink. All neurons that showed a
sharp increase in their activity slightly preceding (~20 ms) and
tightly linked to the onset of saccades directed into their movement
field were considered saccade-related and were therefore subjected to
further analysis. The location and extent of a cell's movement field
was determined from the movement field scan data by plotting the number
of spikes, counted from 20 ms before saccade onset to saccade offset,
as function of saccade amplitude and direction. Quantitative
descriptions of the movement fields were obtained by fitting
two-dimensional Gaussian activation profiles to the cells' activity as
function of saccade vectors in collicular motor map coordinates (see
Ottes et al. 1986 for extensive details) (goodness of
fit: r typically between 0.85 and 0.98).
The raw spike trains were converted into smoothed representations of a
cell's instantaneous firing rate by constructing spike density
functions (D). To that end, all spike events in a trial were
substituted by Gaussian pulses of width = 4 ms and height 1/(
) and summed to produce a continuous function of
time (MacPherson and Aldridge 1979
; Richmond and
Optican 1987
). Large values of the spike density function
represent a high probability of spike occurrence, and the peak of the
function represents the peak discharge of the cell (in spikes/s). To
estimate the duration of the saccade-related burst during individual
saccades more robustly, the width of the Gaussian was increased to
= 10 ms (see RESULTS).
Dynamic motor error (ME) was defined as the difference between saccade endpoint and instantaneous eye position. The average phase relations between spike density and dynamic motor error shown in Figs. 12, C-E, and 13, A-F, were obtained by averaging the spike density and dynamic motor error signals as function of time for series of matched eye movements. It was not always possible, however, to find a sufficient number of perturbed responses with closely matched movement profiles. To circumvent this problem, the spike density function of each trial was resampled as function of the declining radial motor error using spline interpolation. In this way, all responses with matched saccade amplitudes and directions could be used to compute the average phase relations for each neuron in Fig. 13, G and H, despite the large variability in movement kinematics.
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RESULTS |
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Single-unit activity was recorded from a series of SRBNs encountered in the intermediate and deep layers of the SC of three monkeys. Twenty-nine of these neurons (PJ: n = 17; SA: n = 4; ER: n = 8) were studied with the use of the blink-perturbation paradigm in which visually evoked saccades were disturbed by air-puff-evoked reflex blinks. Of the 29 SRBNs tested, 25 neurons remained isolated long enough to obtain a full 2-D scan of their movement field as well as a sufficient series of perturbed saccades for the quantitative analysis described in the following text. For the remaining four cells, we gathered sufficient data in at least the blink-perturbation paradigm to verify that they showed qualitatively similar features to the more thoroughly studied set of 25 SRBNs.
Isolated collicular neurons were classified as SRBNs if they showed a sharp increase in their firing rate ~20 ms before and tightly linked to the onset of saccades directed into the cell's movement field, irrespective of other pre- and postsaccadic discharge properties. In saccade trials, most of the cells (25/29) also showed a brief visual response ~70 ms after the visual stimulus appeared inside their receptive field. A prelude of presaccadic activity that could start several tens of milliseconds before the high-frequency, saccade-locked burst was also frequently observed. Cells that were endowed with a considerable amount of long-lead (>100 ms) presaccadic activity also showed a considerable amount of postsaccadic activity over a period of 100 ms after the saccade and were typically encountered at deeper locations from the SC surface. Saccade amplitudes for which the recorded SRBNs were maximally recruited ranged between 8 and 50°, except for four cells in the caudal SC which had no optimum for saccade amplitudes <70°. When tested in fixation trials, SRBNs were silent, and they were not recruited when air puff stimuli were presented in fixation-blink trials.
Activity during compensatory saccades
When air puffs were used to elicit a reflex blink near the onset
of saccades, not only were the stereotyped spatial-temporal properties
of saccades disturbed (Goossens and Van Opstal 2000) but
the discharge patterns of SRBNs in the SC also were clearly modified.
This is illustrated in Fig. 1, which
compares the discharge of a saccade-related neuron (sa6703)
in the caudal SC during a control saccade (~60° to the left; Fig.
1A) and during a blink-perturbed saccade that landed close
to the extinguished target (Fig. 1B). Figure 1B
shows, in a qualitative way, the consistent features of blink-perturbed
responses that were obtained in all three monkeys. First, at the onset
of the blink, the eye rapidly deviated from its normal, straight
trajectory (typical latencies ~20 ms relative to the air puff onset
at the eye), and no sharp increase in the cell's discharge was
observed around the eye-movement onset. Second, as the cell continued
its low-level discharge, the eye movement continued, and the
perturbation in both direction and velocity was compensated in complete
darkness. Finally, the increase in movement duration to reach the
target was matched by a comparable increase in the duration of the
cell's discharge.
|
To document the reproducibility of these findings among our
sample of collicular neurons, Figs. 2 and
3 show the activity of two other
representative SRBNs during a series of control trials and a series of
perturbation trials. The data plotted in Fig. 2 were recorded from a
neuron (pj5203) that was found in the central region of the
SC motor map. Saccade vectors were matched in amplitude and direction,
and data are aligned on different events, from top to
bottom: saccade onset (Fig. 2, A-D), saccade
offset (Fig. 2, E and F), and air puff onset
(Fig. 2G). As shown in Fig. 2, right, the cell
showed a brisk burst discharge for control saccades of optimal
amplitude and direction ([R, ] = [20, 60] deg). The onset of the saccade-related burst ("motor burst" for short)
preceded the saccade onset by ~20 ms (Fig. 2D) and peaked
shortly before saccade onset. Subsequently the discharge declined
sharply during the saccade until it stopped when the saccade ended
(Fig. 2F). Neurons with such behavior have also been
referred to as clipped burst neurons (Munoz and Wurtz
1995
; Waitzman et al. 1991
). During perturbation
trials (Fig. 2, left), the cell's burst discharge was
clearly disturbed along with the saccade kinematics. As may be observed
in Fig. 2C, the neuron typically showed an irregular discharge around movement onset, except in two trials where the cell
showed a near-normal burst (top rows of the spike rasters). The irregular, lower-frequency discharge was associated with the low-velocity saccades, whereas the two clear bursts were associated with the two high-velocity saccades (clearly identifiable in Fig. 2A). Figure 2G shows the same responses aligned
with air puff onset. Note that the cell's (upcoming) burst activity
was transiently suppressed shortly after the air puff arrived at the
eye. About 30-40 ms after the air puff onset, the cell resumed its
activity, and it continued its discharge until the perturbed saccade
ended. The latter can be readily observed in Fig. 2E, which
shows the data aligned with saccade offset. Figure 2H
compares the two conditions by showing the difference between the
average spike-density function for control and perturbed trials (data
aligned with eye-movement onset). As was typically observed, the
resulting difference waveform was endowed with an initial negative
component, followed by a positive phase that ended with the average end
of perturbed saccades. The biphasic profile illustrates both the
initial suppression as well as the prolongation of the cell's burst
discharge in the perturbed condition. Note that the negative component
leads the eye-movement onset because the air puff typically preceded
the onset of the impending saccade, thereby interfering already with the cell's presaccadic discharge.
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Figure 3 shows comparable data obtained from an SRBN
(er1101) that was endowed with long-lead presaccadic
activity. As may be observed in Fig. 3D, this prelude
activity was followed by a more intense burst just before and during
control saccades of optimal amplitude and direction ([R,
] = [14, 150] deg). The discharge peaked at saccade onset and
then declined rapidly toward the end of the saccade. After this
high-frequency burst, the neuron showed a gradual decline of
postsaccadic activity over a period of ~250 ms (i.e., unclipped
discharge; see Fig. 3F). Collicular neurons that exhibit
such temporal discharge characteristics have also been named buildup
neurons (Munoz and Wurtz 1995
). During perturbation
trials (Fig. 3, left), the cell's activity was clearly suppressed within ~10-20 ms after the air-puff onset (Fig.
3G). As the air puffs were presented prior to the impending
saccade, the onset of the suppression preceded the actual
saccade onset (Fig. 3C), except in the one trial (top
row of the spike raster) where the perturbation occurred toward
the end of the saccade (see Fig. 3A). Following a near
complete cessation of activity, the neuron resumed its discharge
~30-40 ms after the air-puff onset (Fig. 3G). Although
the discharge of this neuron did not end at saccade offset, it may be
inferred from the spike rasters in Fig. 3E that it showed an
increased firing rate until the end of the perturbed eye movements.
This prolongation of the cell's saccade-related activity is also
evident from the difference between the average control and perturbed
response (Fig. 3H), which drops to zero around the mean
offset of the perturbed saccades.
Suppression and resumption of SRBN discharge
Since the air puffs often interfered already with the cells'
pre-saccadic discharge, the impression was obtained that the changes in SRBN activity were the underlying cause rather than the
consequence of modified saccade kinematics. To gain further insight
into the possible mechanism that could underlie the suppression of SRBN
discharge, we also examined responses in which the saccade was
accompanied by a gaze-evoked blink. As shown in the companion paper
(Goossens and Van Opstal 2000), the spatial-temporal
perturbation resulting from gaze-evoked blinks were qualitatively
similar to those obtained with air-puff-evoked blinks.
Figure 4 compares the responses of two different SRBNs that were recorded under both air-puff- and gaze-evoked blinking conditions. The two cells, er0902 (Fig. 4, A and B) and pj6802 (Fig. 4, C and D), were isolated in the left and right SC, respectively. Note that the burst activity of both cells was strongly suppressed following the onset of reflex blinks that were evoked by air puff stimulation of the left eye (Fig. 4, A and C). By contrast, no transient suppression was observed following the onset of gaze-evoked blinks (Fig. 4, B and D; thick traces), which had a comparatively small influence on the discharge of the SRBNs. Note that this difference in SRBN discharge is also reflected in the saccade kinematics, which were less dramatically disturbed by gaze-evoked blinks. The latter may be inferred from the control data that are superimposed in Fig. 4, B and D (thin traces). On average, also the air-puff- and gaze-evoked blinks were different. However, by selecting a subset of responses with comparable eyelid traces, it could be excluded that the differences in SRBN discharge were merely due to differences in blink magnitude (data not shown).
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As illustrated by the preceding examples, SRBNs showed a transient decrease in their discharge following the onset of an air puff. Although present in most cells tested, this suppression was often far from complete and variable from trial to trial. Moreover, at the time of the air puff (fixed re. target onset, see METHODS), the amount of presaccadic activity was variable due to considerable scatter in the onset latencies of the motor burst with respect to target onset (see Fig. 4, A and C). It was not possible therefore to quantify the onset latency and the duration of this phenomenon for each neuron with the same accuracy.
To obtain at least a crude estimate of the time course of the
suppression and subsequent resumption of SRBN activity, we analyzed the
discharge of those SRBNs (n = 7) that exhibited a
strong suppression in a large number of trials. To that end, the
spike-density functions from all perturbation trials in a recording
session, except the ones in which the perturbations occurred very early
or very late in the burst, were averaged (n between 20 and
80; = 4 ms) and subsequently normalized with respect to the
mean. Figure 5, A and
B, shows the results of this procedure for each neuron (thin curves) when data were aligned to air puff onset and blink onset, respectively. Averaged data of the seven neurons (thick curves) are
superimposed. As may be inferred from these data, the suppression starts, on average, ~10 ms after the air puff onset and leads the
blink onset by an approximately similar amount. About 10-30 ms after
the blink onset, the SRBNs resumed their discharge. Some caution is
called for with regard to the interpretation of the data in Fig.
5B because movements of the contralateral, unstimulated eyelid were used to detect blink onsets. However, as indicated in the
companion paper (Goossens and Van Opstal 2000
), it is
reasonable to assume that there is no significant latency difference
between ipsi- and contralateral eyelid movements as the short-latency, uncrossed R1 component of the primate blink reflex hardly contributes to movements of the eyelid (Bour et al. 2000
).
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Quantitative analysis of the saccade-related discharge
Unlike in previous saccade interruption paradigms, the evoked
perturbations in the present experiments typically affected the entire
saccade. Nevertheless the data presented so far indicate that the
response properties of SRBNs during blink-perturbed saccades showed
qualitatively similar features as have been observed during interrupt
saccades (Keller and Edelman 1994; Munoz et al.
1996
). Therefore to facilitate a comparison between the
interruption data and the present data set, we started out with a
comparable quantitative analysis.
BURST DURATION.
The raw data in Figs. 1-3 indicate that the SRBNs showed a prolonged
burst discharge until the perturbed eye movement ended. To quantify
this feature, we determined the duration of the motor burst for each
individual saccade into the cell's movement field. For neurons showing
clipped or partially clipped activity in the control condition
(n = 13), the burst duration was measured from 20 ms
before saccade onset to the time when the spike density fell below 1%
of the peak value. To determine, in a comparable way, the duration of
the high-frequency motor bursts in cells with an unclipped discharge
pattern (n = 12), we first estimated the end of their
high-frequency burst in the averaged control data by looking at the
transition point between the high- and low-frequency discharge (see
Fig. 6 for an illustration). The ratio
between the peak spike-density and the spike density at the end of the
burst, thus derived from the averaged control data, was subsequently
used to detect the duration of each individual burst (for the different
neurons, actual cutoff values ranged between 10 and 30% of the peak
discharge rate). The latter was done by a computer algorithm that
computed spike density functions with a of 10 ms (see
METHODS). Because of the reduced firing rates during
perturbed saccades (see e.g., Figs. 2 and 3; see also the quantitative
data in following text), this relatively wide kernel was needed to
obtain a more robust detection in both the perturbed and unperturbed
condition (same
used in both conditions and for all neurons).
Although this procedure tends to overestimate the absolute duration of
individual bursts (depending on the actual cutoff value), this
overestimate is virtually fixed (within ~5 ms) across trials. It
therefore has a negligible influence on the slopes and correlations of
the linear regression analysis reported in the following text.
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BURST MAGNITUDE. The raw data in Figs. 1-3 illustrate that the discharge rates were substantially lower during blink-perturbed saccades. However, the impression was obtained that the number of spikes in the motor burst was approximately similar for perturbed and control saccades. To better quantify this property, we counted the number of spikes in each burst for saccades of optimal amplitude and direction using a time window that ranged from 20 ms before saccade onset to saccade offset. For comparison, the total number of spikes before, during, and after the saccade also were quantified by counting all spikes over a fixed 800-ms window starting 100 ms after target onset (which excluded visually evoked activity). Perturbation trials in which the saccade kinematics appeared to be hardly affected were excluded from this analysis (typically <5-10% of the trials).
Figure 8 illustrates the results of this analysis for the two neurons shown in Fig. 6. Plotted are histograms of the number of spikes in the burst and the total number of spikes on individual control trials (top) and perturbation trials (bottom). Although the average number of spikes in the burst was slightly higher for perturbed saccades (t-test, P < 0.01), the difference between the two conditions was remarkably small. This result was obtained for both neurons (Fig. 8, A and B, and E and F), even though the number of spikes in the burst of the long-lead SRBN (er0904) was only a limited fraction of its total number of spikes (compare Fig. 8, E and F with G and H). The latter readily indicates that the long-lead SRBN also showed a considerable amount of pre- and postsaccadic activity (see also Fig. 6D). Note, however, that the total number of spikes for control responses and perturbed responses in the 800-ms window was very similar too (Fig. 8, G and H). For the short-lead SRBN (pj6701), the number of spikes in the burst and the total number of spikes was very similar (compare Fig. 8, A and B with C and D), which is readily understood from the clipped nature of its discharge (see also Fig. 6B and DISCUSSION).
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Intrasaccadic discharge in relation to the 2-D saccade trajectory
The observed linkage between saccade duration and burst duration (Figs. 6 and 7) could be expected if the SC is part of the local feedback loop that is thought to control the saccade trajectory (see INTRODUCTION). To further investigate this possibility, we therefore analyzed the intrasaccadic discharge of collicular neurons in relation to the 2-D saccade trajectory.
SPATIAL PROPERTIES.
Figure 11 shows a typical example of
the results of this analysis for an SRBN that was most active for
upward control saccades (movement field center [R, ]
[35, 90] deg). Figure 11, A-C, shows the 2-D
trajectories of a perturbed saccade and a control saccade toward the
same target (Fig. 11A; T at [R,
] = [27,
60] deg) as well as simultaneous records of the cell's discharge
during each of these movements (Fig. 11, B and C,
respectively). Figure 11, D-F, shows data of two visually
evoked control saccades that matched to the two subsequent eye-movement
phases that were present in the perturbed saccade. Comparing the
perturbed response in Fig. 11B to the control response in
Fig. 11C, one may observe that the duration of the
saccade-related discharge during the perturbed response exceeded the
normal burst duration by far. The most important feature, however, is
that the cell resumed its burst activity after the blink-related
suppression even though the direction of the compensatory
movement (rightward) did not match the direction of the cell's movement field (upward). The latter becomes evident by
noting that the compensatory movement in Fig. 11B was almost equivalent (albeit slower) to the rightward saccade plotted in Fig.
11E (cf., Fig. 11, A and D) and by
noting that the cell was not at all recruited for this control saccade.
Because the neuron resumed its burst activity, we conclude that the
compensatory movement was still part of the initial saccade program
specifying an eye displacement up and to the right. If the compensatory
movement had instead been generated by a new motor command specifying a rightward eye displacement, the discharge of the neuron should have
stopped completely when the eye moved rightward (see Fig. 11E). Note that these results closely resemble the results
obtained in the interruption paradigms used previously (see
INTRODUCTION) except that in this case the direction of the
compensatory movement has been altered too. The initial phase of the
perturbed response is also quite interesting. In this part of the
response, the eye movement was directed into the cell's
movement field (upward). As may be observed in Fig. 11, A
and D, the amplitude and direction of this initial movement
were comparable with that of the upward control saccade. Note, however,
that during the upward movement in Fig. 11B, the cell showed
a near-complete cessation of activity (see first 50-60 ms), whereas
the cell discharged vigorously for the upward control saccade plotted
in Fig. 11F. Because the SRBN showed a near-complete
cessation of activity even though the eye moved in the optimal
direction of the cell, we conclude that the SRBN discharge did not
mediate the upward trajectory perturbation. If the upward movement had
instead been generated a (modified) collicular command specifying an
upward eye displacement, the cell should have continued its vigorous
discharge during the upward movement (see Fig. 11F).
Summarizing these results, it appears that the actual 2-D trajectory of
the perturbed saccade was not reflected in the SRBN discharge pattern.
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DISCHARGE DYNAMICS.
For all neurons that could be tested in detail, phase plots were
constructed of instantaneous spike density versus radial motor error
(ME; difference between desired and current eye
displacement) by following the same method utilized in previous studies
(Keller and Edelman 1994; Munoz et al.
1996
; Waitzman et al. 1991
). The majority of
these cells (n = 17) showed a monotonic decline of spike density as function of decreasing radial motor error for control
saccades toward the center of their movement field and were therefore
subjected to a further analysis. Since blinks not only modified the
saccade kinematics but also changed the 2-D saccade trajectories,
additional phase plots were made of spike density versus the respective
horizontal and vertical motor-error components. Spike density functions
were computed with a
of 4 ms and shifted backward in time by 4-8
ms to obtain the best linear decline as function of radial motor error
for control responses (Waitzman et al. 1991
).
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Activity during saccades showing no compensation
So far we have presented an analysis of the SRBN discharge
properties during saccades that compensated for the blink-related perturbations. Typically the SC cells remained active throughout these
movements, irrespective of the instantaneous eye-movement trajectory.
It is therefore of interest to also consider what happened in cases
where compensation was absent (see also Goossens and Van Opstal
2000). Although this latter response mode was quite uncommon
(usually no more than 15% of the trials), it was typically found in
those cases that the cell stopped firing well before the eye-movement
offset. Examples of this behavior are shown in Fig.
14.
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Figure 14A depicts the 2-D trajectories of four
blink-perturbed saccades (· · · ; mean indicated by
) that showed compensation for the disturbance
(mainly in velocity). The cell's prolonged burst discharge until the
end of these saccades into its movement field (center at
[R,
] = [40, 200] deg) is plotted in Fig.
14B. Figure 14, C and D, shows the
data obtained in five perturbation trials where no compensation
occurred. Rather after the initial movement toward the target, the eye
started moving upward, a direction that was not into the cell's
movement field (leftward; not indicated). It can be clearly observed
that in these cases the cell's initial burst discharge stopped as soon
as the eye stopped moving toward the target.
These observations raised the question what would happen in the
converse case when a nongoal-directed movement would be made into a
cell's movement field. We therefore attempted to elicit such eye
movements in the direction of the preferred vector of several neurons
studied, but sufficient data could be obtained in only three recording
sessions. It is nevertheless interesting to consider the results of
this particular experiment, which is illustrated in Fig.
15 for one of these neurons. Figure
15A depicts blink-perturbed saccades toward target T1, which
was flashed on the horizontal meridian. Note that all movements were
goal-directed and showed compensation for the blink-related
perturbation. Despite the disturbances, the neuron (er1101)
showed a brisk discharge during these movements, which were directed
into the movement field (optimum at [R, ] = [14, 150]
deg). Figure 15B shows the cell's response during a series
of control saccades made outside its movement field. As one may readily
infer from this figure, the neuron was completely silent during these
movements. Figure 15C shows blink-perturbed eye movements
that were obtained while the animal was required to make saccades
toward T2, but no compensation occurred. Luckily the resulting eye
movements in these particular trials were directed into the cell's
movement field, and they were also quite comparable to the ones shown
in Fig. 15A. Note, however, that the cell's burst discharge
remained absent (Fig. 15C). The two other SRBNs showed a
similar behavior. These data therefore support the idea that SRBNs are
recruited only for planned movements into their movement fields.
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DISCUSSION |
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In the present experiments, we have investigated the influence of blinking on the saccade-related discharge patterns in the intermediate and deep layers of the SC. The results demonstrate, for the first time, that trigeminal reflex blinks have a profound influence on the saccade-related discharge of collicular SRBNs. In summary, it was found that ~10 ms after the air puff reached the eye, SRBN activity was briefly suppressed, ~10 ms before the onset of the evoked blink reflex; all recorded SRBNs resumed their discharge shortly (10-30 ms) after the blink onset; all SRBNs continued their discharge for goal-directed saccades into their movement field, irrespective of the saccade duration and irrespective of the instantaneous eye-movement direction; the duration of the high-frequency burst was approximately matched to the overall saccade duration for the majority of cells, regardless of their pre- and postsaccadic discharge properties; although the saccade kinematics and trajectories were both profoundly affected and variable, the number of spikes in the burst was remarkably similar for control and perturbed movements, whereas the mean firing rate was strongly reduced (~50%); for most cells, mean firing rate in the burst and mean eye velocity were well correlated; the monotonic relation between spike density and dynamic motor error, often observed for control saccades, broke down for perturbed saccades; large changes in instantaneous eye-movement direction were not reflected in the instantaneous discharge rate of SRBNs; SRBN activity stopped prematurely when saccades showed no compensation; and finally SRBNs remained silent when eye movements made into the cells' movement field were not part of a planned movement.
Taken together, the data presented in this paper and in the companion
paper (Goossens and Van Opstal 2000) show that reflex blinks change many parameters: saccade latency, eye velocity, saccade
duration, and saccade trajectories as well as SRBN firing rates and
SRBN burst duration. The only two variables that remained virtually
unaffected were the overall saccade displacement vectors and the number
of spikes in the burst. Our findings therefore strongly suggest that
the number of spikes in the burst of collicular SRBNs specify the
desired displacement vector of the eye rather than its actual 2-D
trajectory. The data also indicate that the observed perturbations of
the saccade trajectories are compensated by mechanisms that act
downstream from the motor SC rather than by local feedback through the
SC. This hypothesis will be discussed in the subsequent sections.
Saccade-blink interactions
Previous experiments have shown that trigeminal reflex blinks are
suppressed by excitation of the SC presumably because the SC excites a
nonsaccadic pathway that inhibits the reflex blink circuitry
(Basso and Evinger 1996; Basso et al.
1996
; Gnadt et al. 1997
). The results of the
present study show that reflex blinks (or blink-evoking air puff
stimuli), in turn, inhibit saccade-related activity of the SC. Thus the
picture of an antagonist interaction between the saccade and blink
systems emerges.
Nevertheless, (large) saccades tend to be accompanied by blinks
(Evinger et al. 1991; Zee et al. 1983
),
the gaze-evoked blinks, which may result from a linkage between the
saccadic and blink systems (Evinger et al. 1994
).
Furthermore despite the suppressive effect on SRBN activity,
air-puff-evoked blinks yielded reduced saccade latencies
(see Goossens and Van Opstal 2000
). Presumably, this
effect results, at least in part, from saccade-blink interactions at a
different level in the premotor circuitry. It has been shown that
blinks are accompanied by a pause in the tonic OPN discharge (Cohen and Henn 1972
; Fuchs et al. 1991
;
Mays and Morrisse 1994
). As a result, the reduced firing
rates of collicular SRBNs (Fig. 9B) can still gain access to
the saccadic burst generator, which is otherwise inhibited by the OPNs.
Apparently, these low collicular activation levels also result in much
slower saccades (e.g., Figs. 2 and 3 and 10) (see also Berthoz
et al. 1986
; Van Opstal and Van Gisbergen 1990
).
Suppression of SRBN discharge
An interesting feature that was observed in most of the recorded SRBNs was a brief suppression of their discharge following the onset of an air puff (Figs. 2-5). Also the mean firing rates were reduced considerably in the majority of cells (Fig. 9). Our experiments provide no direct evidence concerning the mechanisms underlying these phenomena.
TRIGEMINOTECTAL PATHWAY.
One possibility is that the observed suppression is due to afferent
input from principal sensory and spinal trigeminal neurons that
innervate the SC (e.g., Huerta et al. 1981, 1983
;
Wiberg et al. 1987
). This possibility is supported by
our observation that SRBN activity was only mildly affected by
gaze-evoked blink, whereas a strong suppression was observed during
air-puff-evoked blinking in about one-third of the cells (Figs. 4 and
5). Also the latency of this effect, estimated at ~10 ms relative to
air puff onset (Fig. 5), seems to be roughly in line with what could be
expected for a trigiminotectal pathway in rhesus monkey. However, it is
currently unknown whether the SRBNs in monkey receive
inhibitory trigeminal signals, either directly or indirectly
(via interneurons). Earlier work, by e.g. Redgrave et al.
(1996)
, suggests that trigeminal afferents to the SC are
excitatory because their study showed that SC neurons
increase their discharge in relation to nociceptive and
wide-dynamic-range facial stimuli in anesthetized rat. It is unclear,
however, whether they recorded from movement-related cells analogous to
SRBNs. In our present experiments, we obtained no evidence that SRBNs
in the monkey SC are excited by trigeminal signals.
CEREBELLOTECTAL PATHWAY.
An alternative possibility is that a cerebellotectal pathway
mediates the suppression of SRBN activity. As reported by May et
al. (1990), the monkey SC receives cerebellar input via two pathways. One, the fastigiotectal pathway, is derived from cells in the
caudal fastigial nucleus that project bilaterally to the rostral SC.
The other pathway is derived from cells in the interposed nucleus and
the dentate nucleus, which project to the intermediate and deep layers
of the contralateral SC. In cat, cerebellar dentate neurons are related
to both saccade and eyelid parameters (Gruart and
Delgado-García 1994
). However, it remains to be
determined whether dentate projections to the SC exert a short-latency,
transient inhibitory influence on collicular SRBNs.
NIGROTECTAL PATHWAY.
A third possibility is that the substantia nigra pars reticulata (SNr)
of the basal ganglia is involved. As far as we know, only the SNr is
currently known to have strong inhibitory projections throughout the
motor SC (e.g., Beckstead et al. 1981; Graybiel 1978
; May and Hall 1986
). Many SNr cells
normally decrease their tonic discharge before and during a saccade,
thus allowing a brisk burst discharge by collicular SRBNs
(Hikosaka and Wurtz 1983
). Recent studies in rat have
furthermore indicated that the amplitude of reflex blinks can be
modulated through a nigro-tectal-spinal pathway (Basso and
Evinger 1996
; Basso et al. 1993
, 1996
;
Evinger et al. 1993
). Inactivation of the SNr by
microinjections of muscimol, for example, yielded a suppression of
reflex blinks in rats (Basso et al. 1996
) as did
electrical microstimulation of the SC in both rats and monkeys
(Basso et al. 1996
; Gnadt et al. 1997
).
Microinjections of muscimol into the rat SC, in turn, led to an
enhancement of reflex blinks (Basso et al. 1996
). In
addition, neurological disorders like Parkinson's and Huntington's
disease give rise to both marked oculomotor deficits, such as slow
saccades, and an abnormal reflex blink excitability that may be partly
due to a disturbed SNr input to the SC (Basso and Evinger
1996
; Basso et al. 1996
;Bronstein and
Kennard 1985
; Hikosaka and Wurtz 1983
;
Leigh et al. 1983
; Rascol et al. 1989
;
White et al. 1989
). Taken together, it is conceivable
therefore that the SNr could be involved in modifying the SRBN
discharge during blinks. Perhaps reflex blinks give rise to a transient
excitation of SNr cells, causing a suppression of SRBN burst discharge.
The latter, in turn, would facilitate reflex blinks at the time of a
saccade. A similar hypothesis has been put forward by McHaffie
et al. (1989)
, who proposed a model of competitive interactions
between SC-mediated orienting and defensive reflexes, in which the
orienting responses are suppressed by inhibition via the basal ganglia
while withdrawal responses are initiated. However, it remains to be
shown that blinks actually influence the activity of SNr cells.
INTRACOLLICULAR MECHANISMS.
A transient suppression of SRBN activity also occurred when
intrasaccadic microstimulation was applied in the rostral SC
(Munoz et al. 1996) or in the OPN region (Keller
and Edelman 1994
). In both cases, the observed suppression is
thought to result from an inhibition by rostral SC cells that were
stimulated either directly (Munoz et al. 1996
) or
indirectly through retrograde activation (Keller and Edelman
1994
). Could it be, therefore, that the blink-related SRBN
suppression in the present study was due to an excitation of rostral SC
cells? We regard this possibility as unlikely. The rostral zone is
involved in active fixation (Munoz and Guitton 1991
;
Munoz and Wurtz 1993a
,b
) and has extensive excitatory projections to the OPN region (Büttner-Ennever et al.
1999
; Gandhi and Keller 1997
; Paré
and Guitton 1994
). The OPNs, in turn, are known to pause for
blinks (Cohen and Henn 1972
; Fuchs et al.
1991
; Mays and Morrisse 1994
). It is more
likely, therefore, that rostral SC neurons, like OPNs, will pause for
blinks. This would be more in line also with the observed reduction of
saccadic latencies (see Goossens and Van Opstal 2000
).
It is also unlikely that the OPNs would mediate the suppression of SRBN
activity since these neurons do not project to the SC
(Büttner-Ennever and Büttner 1988
).
Resumption of SRBN discharge
The question as to which mechanism underlies the resumption of
SRBN activity shortly after blink onset (Fig. 5B) cannot be answered on the basis of the present experiments. One possibility could
be that an external excitatory signal remains (Munoz et al.
1996). Alternatively, since the suppressive effect of blinking was often far from complete (Fig. 5), it could be that intrinsic properties of the collicular network, such as local excitatory interactions, underlie the resumption of SRBN discharge.
Nevertheless it can be concluded that the resumed discharge was closely linked to the actual oculomotor behavior. First, the (two- to threefold) increase in duration of the perturbed movement was well correlated with the increase in duration of the motor burst (Figs. 6 and 7). Second, despite a substantial reduction in the mean discharge rate, the number of spikes in the burst associated with perturbed saccades was very similar to that in the burst for control saccades (Figs. 8 and 9). Third, the reduction in mean firing rate was well correlated with the reduction in eye velocity during perturbed saccades (Fig. 10). These findings clearly reflect the fact the SRBNs are a major source of input to the brain stem saccade generator. Yet as will be discussed in the following text, these results do not necessarily imply that the SRBNs receive feedback about the saccade trajectory.
Comparison with previous perturbation studies
As reviewed in the INTRODUCTION, previous studies have
used electrical microstimulation of either the OPN region
(Keller and Edelman 1994) or of the rostral SC
(Munoz et al. 1996
) to investigate the influence of
perturbations in saccade kinematics on the discharge patterns of
saccade-related neurons in the SC. These studies revealed a transient
cessation in SRBN activity, as well as an intrasaccadic fixation of the
eyes. In the case of OPN stimulation, the rostral SC is presumably
excited through retrograde activation (Keller and Edelman
1994
). Conversely, rostral SC stimulation probably activates
also the OPNs (Munoz et al. 1996
; Paré and
Guitton 1994
; Raybourn and Keller 1977
). Because
of these side effects, it could not be decided whether reactivation of
the OPNs or cessation of SRBN activity caused the saccade interruption.
As discussed in the preceding text, the air-puff-evoked blinks are
instead more likely to cause suppression, rather than excitation, of
both the OPNs and the rostral SC in the present experiments. The
spatial-temporal saccade disturbances resulting from blinks are also
quite different from the brief stimulation-induced saccade
interruptions (see Goossens and Van Opstal 2000
, for details).
Despite these differences, other aspects of our results are quite
comparable with the interruption data. First, SRBNs resumed their
discharge also after a blink-induced inhibition although neither the
size nor the direction of the compensatory eye movement corresponded to
the cell's movement field (e.g., Fig. 11). The latter observation
further supports the notion that the saccade trajectory is not encoded
by a dynamic shift in the location of activated neurons in the SC motor
map (see Anderson et al. 1998). Second, as in the
interruption experiments, burst duration remained well coupled to total
movement duration (Fig. 7) despite its two- to threefold increase.
Third, for both types of perturbations, the total number of spikes in
the burst was comparable with that for control responses. Especially
for blink-perturbed responses, where the spatial trajectories as well
as the movement kinematics were altered much more dramatically, this is
quite a remarkable finding. Finally, as was qualitatively observed by
Munoz and colleagues, saccade perturbations affected the high-frequency
discharge of long-lead (buildup) and short-lead (burst) neurons in a
similar way. Our present results confirm and further quantify these
observations (Figs. 6, 8, 10, and 13). These data therefore strongly
suggest that both SRBN subtypes fulfill very similar roles in the
control of saccades. Further support for this hypothesis will be
presented in the following text.
Efferent feedback to the motor SC?
FEEDBACK ABOUT THE ACTUAL 2-D TRAJECTORY?
One hypothesis about the activity of collicular neurons is that their
discharge rate encodes dynamic motor error. This idea was inspired by
the observation that the motor burst of many SC neurons ends with
saccade offset and that the discharge rate of these cells decays
monotonically with radial motor error (Waitzman et al.
1991). As reported by Keller and Edelman (1994)
and Munoz et al. (1996)
, this monotonic decay persists
for postinterruption saccades. However, whether these striking
properties are due to some form of efferent feedback from the brain
stem saccade generator remains difficult to decide on the basis of the
interruption data. As argued in the INTRODUCTION, the
kinematics of postinterruption saccades are still highly stereotyped as
inferred from their main sequence behavior (Munoz et al.
1996
). In addition, the saccade trajectories remained unaltered
since no changes in movement direction were induced. Thus except for
the brief stimulation-induced interruption, the changes in the eye
movements were relatively small, whereas the SRBN discharge is
typically endowed with a considerable amount of intrinsic noise (see
e.g., standard deviations of the control curves in Figs. 12 and 13).
FEEDBACK ABOUT AN INTENDED TRAJECTORY?
In the companion paper, we examined the possibility that
blink-perturbed saccades result from a linear superposition of two independent motor commands: an unperturbed saccade command and a pure
blink-related command. It appeared that the 2-D trajectories, but not
the kinematics, of the "reconstructed saccades" (obtained by
subtracting pure blink-associated eye movements from blink-perturbed saccades) were comparable with that of control saccades (see Figure 11 in Goossens and Van Opstal 2000). The observation that
the reconstructed saccades, like control saccades, had approximately straight trajectories is in line with the results of the present study,
which indicate that changes in eye-movement direction are not reflected
in the SRBN discharge (Figs. 11 and 12).
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Number of spikes versus discharge rate
The finding that the number of spikes in the motor burst of
collicular SRBNs is roughly invariant to the spatial-temporal properties of the saccade trajectory (Fig. 9) hints at the interesting possibility that this quantity, rather than the firing rate per se,
represents the desired eye displacement vector. Recent studies on the
effects of electrical microstimulation in the SC also support this
hypothesis. By manipulating either stimulation intensity (Van
Opstal et al. 1990), or the number of stimulation impulses (Stanford and Sparks 1996
), saccade amplitude, but not
saccade direction, was systematically varied between zero and the
optimal amplitude represented at the stimulation site.
The hypothesis would therefore entail that SRBNs encode a straight eye
displacement, the direction of which is determined by the location of
the recruited cells within the SC motor map and the movement amplitude
of which is determined by the number of spikes in the burst. In this
way, the temporal distribution of the SRBN spikes may influence, but
not necessarily encode, the velocity of the saccade. A similar
suggestion follows from Scudder's model of the collicular-brain stem
saccade generator (Scudder 1988).
Note, however, that the amplitude of stimulation-evoked saccades
saturates at a site-specific value even if the electric stimulation is
continued after the saccade (e.g., Robinson 1972).
Similarly the number of spikes in the motor burst is often only a
fraction of the total number of spikes (see e.g., Fig. 8), and many
SRBNs continue their discharge well after saccade offset (see e.g., Fig. 3). Thus a large proportion of the cells' activity does not contribute directly to the saccade.
To gain further insight into the firing properties of the SRBNs, we have extended our spike-count analysis to include also the pre- and postsaccadic discharge. The results for all 25 fully tested cells are summarized in Fig. 17. Figure 17A shows that the total number of spikes (800-ms window; see inset), was also very similar for the two experimental conditions for all cells. Figure 17B shows the burst index, which we defined as the fraction of spikes in the motor burst relative to the total number of spikes (see inset). Note that the burst index is very different from cell to cell (range: 0.25-1.00) and distributed along a continuum. The latter indicates that our cells could not be classified into two separate categories. The spike-count data in Fig. 17C evaluate only the burst together with the postsaccadic spikes (500-ms window; see inset). Note that in this case the slope of the regression line (solid) is not significantly different from 1.00 (P > 0.1) as all data points scatter around the identity line (dashed). This hints at the possibility that the spike count including both burst and postsaccadic activity is the real invariant parameter rather than the saccade-related spike count. Figure 17D shows the clip index, which we defined as the fraction of spikes in the motor burst relative to the number of spikes in the burst and postsaccadic activation period (see inset), for all 25 cells. A clip index of one indicates no postsaccadic activity, whereas a clip index of zero indicates that there was no burst. Note that the clip indices were slightly different for the two conditions, and in line with Fig. 17B, widely distributed (range 0.4-1.0). Thus the tight correlation that is observed in Fig. 17C is the same for all SRBNs, regardless of the pre- and postsaccadic discharge properties.
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In conclusion, our data suggest that the number of spikes in the motor burst is fixed not because the SRBNs are under feedback control but because intrinsic properties of the SC network ensure that these cells generate a (more than) sufficient number of spikes. This in turn guarantees that the brain stem burst generator can complete the eye displacement vector requested by the SC. This theory implies therefore that a mechanism downstream from the SC would count the number of spikes from the SRBN population until a site-specific value is reached, causing reactivation of the OPNs to stop the saccade. Thus the mechanism that apparently determines a fixed number of spikes in the SRBN burst could act entirely downstream from the SC.
Compensatory behavior
Our behavioral data demonstrated that a near-complete compensation
for blink-related disturbances ensured that the eye landed close to the
extinguished target (see Goossens and Van Opstal 2000).
It was argued that this compensatory behavior was due to neural control
mechanisms, rather than to passive elastic restoring forces within the
oculomotor plant. Our present neurophysiological data provide strong
additional support for this view (e.g., Figs. 1-3 and 14).
Two mechanisms could in principle account for the compensatory movement component: local feedback within the brain stem saccade generator or an active reset eye movement that is generated by the blink system itself. On the basis of the current experiments, it is not possible to decide between either possibility. Local feedback could indeed ensure that the blink-induced eye deflections are automatically corrected for but only if these trajectory perturbations result from a blink-related signal that acts within the local feedback circuit. On the other hand, an active reset movement generated by the blink system itself could be added either to the neural drive from the SC or elsewhere in the premotor circuitry.
It is quite unlikely that the SC mediates the eye-movement deflections
since SRBNs are typically suppressed around the onset of a blink (Fig.
5). This is further supported by the data in Figs. 14 and 15, which
indicate that only the site corresponding to the desired movement is
involved. Instead, we believe that the blink-related signal that is
responsible for the 2-D trajectory disturbance interacts with the
saccade system at a level that is downstream from the SC,
but upstream from both the extraocular motoneurons and the
oculomotor neural integrator. The latter is based on the observation
that a blink-associated eye movement often brings the eye to a new
orbital position that is maintained until a correction saccade is made
(see Goossens and Van Opstal 2000 for examples).
We conjecture, therefore, that blink-associated eye movements may
involve neural structures that are parallel to the saccade burst
generator but share the oculomotor integrator as well as the omnipause
neurons. Alternatively, the blink system could even share also saccadic
burst cells in the brain stem. Recordings from burst neurons in the
paramedian pontine reticular formation during blinks (Cohen and
Henn 1972) have provided preliminary support for the latter possibility.
Conceptual model of saccade-blink interactions
Figure 18 provides a simplified summary scheme of the saccade-blink interactions that may explain the observations from the previous and present paper. In short, when the blink system is activated 1) motoneurons that innervate the orbicularis oculi muscle (OO) are recruited to produce a blink. 2) Cells in the entire motor SC are inhibited. As this inhibition gradually subsides, SRBNs at the location corresponding to the overall desired saccade vector resume their activity. Due to remaining suppression, the activity levels in the SRBNs are lower than for control responses. 3) The saccade burst generator in the brain stem is excited (in this scheme biphasically, to account for the return movement of the eyes as well), which in turn shuts off the omnipause neurons. 4) Due to this indirect OPN inhibition (possibly combined with inhibition that is more direct), the burst generator is also excited by the SRBNs. Since blink-related and collicular signals add at this level, the resulting eye-movement trajectory is slow and strongly curved but ends close to the target. 5) SRBNs at a given site in the SC send a burst to the saccade burst generator that contains an approximately fixed number of spikes. 6) If the number of spikes exceeds a site-specific value, the eye movement will stop by reactivation of the OPNs. This OPN activation ensures that the exact number of spikes produced by the SRBNs is not critical.
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ACKNOWLEDGMENTS |
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We thank C. van der Lee for manufacturing the microelectrodes and H. Kleijnen and T. van Dreumel for technical support. We also thank the staff of the central animal facility for taking care of our monkeys. Dr. F. van der Werf is thanked for helpful discussions and for histology of the recording sites. Both anonymous referees are acknowledged for constructive criticism, which improved the paper substantially.
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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