Allgemeine Zoologie und Neurobiologie, Ruhr-Universität, 44780 Bochum, Germany
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ABSTRACT |
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Stuphorn, Veit, Erhard Bauswein, and Klaus-Peter Hoffmann. Neurons in the Primate Superior Colliculus Coding for Arm Movements in Gaze-Related Coordinates. J. Neurophysiol. 83: 1283-1299, 2000. In the intermediate and deep layers of the superior colliculus (SC), a well-established oculomotor structure, a substantial population of cells is involved in the control of arm movements. To examine the reference frame of these neurons, we recorded in two rhesus monkeys (Macaca mulatta) the discharges of 331 neurons in the SC and the underlying mesencephalic reticular formation (MRF) while monkeys reached to the same target location during different gaze orientations. For 65 reach-related cells with sufficient data and for simultaneously recorded electromyograms (EMGs) of 11 arm muscles, we calculated an ANOVA (factors: target position, gaze angle) and a gaze-dependency (GD) index. EMGs and the activity of many (60%) of the reach-related neurons were not influenced by the target representation on the retina or eye position. We refer to these as "gaze-independent" reach neurons. For 40%, however, the GD fell outside the range of the muscle modulation, and the ANOVA showed a significant influence of gaze. These "gaze-related" reach neurons discharge only when the monkey reaches for targets having specific coordinates in relation to the gaze axis, i.e., for targets in a gaze-related "reach movement field" (RMF). Neuronal activity was not modulated by the specific path of the arm movement, the muscle pattern that is necessary for its realization or the arm that was used for the reach. In each SC we found gaze-related neurons with RMFs both in the contralateral and in the ipsilateral hemifield. The topographical organization of the gaze-related reach neurons in the SC could not be matched with the well-known visual and oculomotor maps. Gaze-related neurons were more modulated in their strength of activity with different directions of arm movements than were gaze-independent reach neurons. Gaze-related reach neurons were recorded at a median depth of 2.03 mm below SC surface in the intermediate layers, where they overlap with saccade-related burst neurons (median depth: 1.55 mm). Most of the gaze-independent reach cells were found in a median depth of 4.01 mm below the SC surface in the deep layers and in the underlying MRF. The gaze-related reach neurons operating in a gaze-centered coordinate system could signal either the desired target position with respect to gaze direction or the motor error between gaze axis and reach target. The gaze-independent reach neurons, possibly operating in a shoulder- or arm-centered reference frame, might carry signals closer to motor output. Together these two types of reach neurons add evidence to our hypothesis that the SC is involved in the sensorimotor transformation for eye-hand coordination in primates.
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INTRODUCTION |
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Primates interact with objects in the external
space by using their arms on an every-day basis. These spatially
oriented motor acts include gaze shifts with eyes, head, and body as
well as reaching with the arm. To do this, the incoming visual
information has to be transformed from a retinocentric into an
effector-related coordinate system. Both the skeletomotor and the
oculomotor networks get their visual input via specific pathways
connecting certain parietal and frontal cortical areas subserving the
control of the eye (Tian and Lynch 1996), arm
(Caminiti et al. 1996
) and hand (Murata et al.
1997
; Sakata et al. 1995
). Each type of effector poses different computational problems and differently assorted types
of sensory information are needed to control the movement. During eye
movements, the direction of the movement vector and the torque of the
eyeball coincide. This relieves the brain from an additional
computational step from a kinematic (desired movement) to a dynamic
(forces needed to perform the desired movement) command. In the case of
arm movements, the brain cannot omit such a step because in this system
the relationship between kinematics and dynamics is nontrivial
(Hollerbach and Flash 1982
). Another difference is the
origin of the reference frames for the signals controlling either the
oculomotor or the skeletomotor system. Naturally both are aligned to
their respective effectors. Consequently the oculomotor system refers
to the gaze axis, whereas the skeletomotor system refers to the joints
of the arm.
Nevertheless it is of great importance to align the gaze axis and the
point in space at which the arm is aiming. The great number of
psychophysical studies showing eye-hand interactions is in accordance
with this need to integrate the activity of the main effectors into a
synergistic pattern (Bekkering et al. 1995; Biguer et al. 1982
; Blouin et al. 1996
;
Goodale et al. 1986
; Jeannerod 1988
;
Prablanc and Martin 1992
). For that reason, one should
expect to find nodal points in the brain where the oculomotor and
skeletomotor networks interact.
The superior colliculus (SC) is known to be a crucial part of the
oculomotor system (Schiller et al. 1987; Sparks
and Hartwich-Young 1989
; Wurtz and Goldberg
1971
) and also is involved in the control of head movements
(Cowie and Robinson 1994
; Freedman and Sparks 1997
; Freedman et al. 1996
;
Guitton 1992
; Paré et al. 1994
). Besides this gaze-controlling system, the SC contains a population of
cells involved in the control of goal-directed arm movements (Werner 1993
; Werner et al. 1997a
,b
).
Because the SC contains gaze- and arm-movement-related signals, it
might constitute another region in the brain in addition to parietal
and frontal cortical areas where the control signals for eye and arm
movements can be coordinated (Wise et al. 1997
). If this
coordination hypothesis is correct, the system controlling one of the
effectors (e.g., the arm) should be no longer independent of the state
of the other (e.g., the gaze). Instead one might expect to find a
relationship between the spatial orientation of gaze and the discharge
of arm-movement-related cells in the SC.
To test the influence of gaze direction on arm-movement-related
activity in the SC, we trained two monkeys to reach to a set of eight
targets in two gaze conditions. First, the monkey looked at the target
while he reached to it, and second, he fixated a light-emitting diode
(LED) away from the target he reached to. With these tasks, we
separated gaze and reach and thus were able to show that reach neurons
in the SC were related to target location with respect to gaze axis.
Preliminary reports of the work have been made previously
(Bauswein et al. 1997; Stuphorn et al.
1995
)
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METHODS |
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The experiments were conducted on two male rhesus monkeys (Macaca mulatta, 8 and 9 kg). The animals were seated comfortably in a primate chair with their heads restrained, facing a tangent screen. The distance between the eyes and the screen was 29 cm for the larger and 28 cm for the smaller monkey. The animals were trained to perform a delayed saccade task and two delayed reach tasks toward light spots of 0.8° diam appearing on the screen. A plastic cylinder around the upper and lower arm loosely restrained the nonworking arm in the reach tasks. All procedures were approved by a local ethical committee and followed the European Communities Council Directive of 24 November 1986 (S6 609 EEC) and National Institutes of Health guidelines for care and use of animals for experimental procedures.
Behavioral paradigms
Two different arm movement tasks were used to probe the
relationship of a cell to reach movements. The first of the two tasks in this study is identical to the delayed reach task used by
Werner et al. (1997a) to identify reach-related neurons
in the SC. Here we name it "saccade-reach" (SR) task in contrast to
the second task, the "fixation-reach" (FR) task. The general
outline of the two tasks is shown in Fig.
1. Both the SR and the FR task begin in
the same way. The monkey has to touch a metal bar and to fixate a
fixation light appearing on the screen. After a randomized interval (1-1.4 s), a target light was turned on. From here on the two tasks
differed. In the SR task, the fixation LED was extinguished after a
randomized delay (0.5-0.9 s). In response the monkey made a saccade to
the illuminated target and fixated it (Fig. 1, left). After
a second randomized delay (0.5-1.4 s), a tone came on that instructed
the monkey to reach toward the fixated target. In the fixation reach
task, the starting cue for the arm movement (the acoustic
GO signal) was given after a randomized delay (1-1.4 s)
while the fixation light on the screen remained on. The monkey had to
maintain fixation while he reached to the peripheral target (Fig. 1,
right). After touching the target for ~1 s, the monkey returned its arm to the initial starting position at hip level and
received a liquid reward. The delayed saccade task and the two reach
tasks were all performed in alternating blocks of at least five trials.
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The targets for the arm movements were an array of eight metal knobs, each containing an LED. For the first monkey (monkey C), the eight targets were arranged on a circle with a radius of 15° centered on the fixation point at the monkey's eye level. For the second monkey (monkey S), the fixation light could appear at three sites, i.e., either centrally (F1 like in monkey C) or 19° lateral from the body midline (F2) or 19° below eye level (F3). Here the eight targets were arranged at a distance of 15° on the four corners of three squares around the fixation points. The knobs located between fixation points provided a reach target during fixation of either (see Figs. 4 and 6, scheme in the bottom right corner). Both arrays allowed to compare neuronal activity while the stimulus was at the preferred extrafoveal position with the activity while the target was at the fovea to calculate the gaze dependency index (see following text). In both tasks, the monkey received a liquid reward after correctly finishing the trial. The monkey's eye position was recorded and controlled throughout the task. During the fixation periods, the monkey had to maintain its gaze within a window of ±2.5° surrounding the light. If the monkey did not fulfill these criteria, the task was aborted and a new trial was started. The touch and release of the touchbar and reach targets caused a digital pulse that was used as a behavioral trigger event. These events were used for the on-line control of the animal's behavior as well as stored on computer disk.
In addition to these two reach tasks, we also used a simple delayed saccade task as an initial test of whether a newly isolated neuron had a relationship to eye movements.
During recording days, the monkeys only received liquid (water or apple juice) in the experiments and worked until satiated. After the experiments, the monkeys were returned to their home cage where they could socialize with other monkeys kept in the same group. The weight and overall health of the monkeys were monitored carefully, and on days without recording, free access to water was allowed.
Surgery
After training in the reaching task, the monkey was
anesthetized with ketamine hydrochloride (10 mg/kg im) followed by
pentobarbital sodium (25 mg/kg iv). Atropine (1 mg) and supplementary
doses of pentobarbital sodium were administered intravenously. Under aseptic conditions, a stainless steel head holder was implanted on the
animal's skull, and a recording cylinder was placed on the midline
over the occipital pole, tilted backward 45° from the vertical.
Search coils were implanted under the conjunctiva around each eye
(Fuchs and Robinson 1966; Judge et al.
1980
). Electrocardiogram, body temperature, blood pressure, and
SPO2 were monitored during the surgery.
Analgesics and antibiotics were delivered postoperatively for 1 wk.
Recording
Extracellular recordings of single neurons were made with
glass-insulated tungsten electrodes (2-3 M). The electrodes were lowered by a microdrive (Narishige) within a guide tube through the
dura. The microdrive was mounted on the chamber whereby the electrodes
penetrated the SC layers approximately perpendicular due to their 45°
forward angle. Single-unit discharges were separated using a
time-amplitude window discriminator and sampled with 1-ms time
resolution. The collicular surface, which could be identified reliably
by vigorous neuronal responses to visual stimuli presented at specific
locations in the contralateral visual field, provided the reference
point for the coordinates of the penetration. The depth of the
hydraulic drive and the coordinates of the visual receptive field were
noted. Then the electrode was advanced further through the midbrain
while the monkey performed arm movements. We tested each well-isolated
unit with the SR and FR task whether its discharge was related to arm movements.
Eye position was measured with a magnetic search coil system (Remmel). Separate horizontal and vertical eye position signals were sampled with a frequency of 500 Hz. These eye-position signals also were used to ensure a stable fixation during the tasks. Figure 2 indicates that this was indeed the case. It gives an example of the eye position recordings during both tasks from the second monkey. The data are not corrected for inhomogeneities in the magnetic field. Figure 2A shows the saccades in the SR task from a central point toward the eight targets, whereas in the FR task, the gaze clearly remains on the three fixation points (Fig. 2B).
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Electromyographic (EMG) activity during the tasks was recorded differentially with intramuscular wire electrodes (0.05 mm diam, Teflon coated) that were inserted transcutaneously with hypodermic needles (27 gauge) under topical application of a local anesthetic (Xylocain). The EMGs were band-pass filtered and rectified before storage. The following muscles were recorded simultaneously with the neurons: M. biceps brachii (Bic), M. deltoideus anterior (ADl), M. deltoideus medialis (MDl), M. deltoideus posterior (PDl), M. infraspinatus (Inf), M. latissimus dorsi (Lat), M. pectoralis (Pec), M. rhomboideus (Rho), M. sternocleidomastoideus (Ster), M. supraspinatus, M. teres major (TMj), M. trapezius (Trap), M. triceps (Tri).
All the recorded data (behavioral events, eye position, neuronal discharge, EMG) were fed into an interface (CED 1401+, Cambridge Electronic Design), converted into digital data, and stored on a computer disc.
Data analysis
Average time histograms of neuronal activity triggered on different behavioral events were accumulated routinely and visually inspected to classify cells as members of the following classes: visual (V), saccade-related (S), fixation (F), and reach-related (R) neurons. The discharge of reach-related cells was analyzed from the GO cue to target contact (over the combined reaction and movement time). All reach-related discharges in the SC occurred in this time window. To quantify the neuronal activity, we first counted the action potentials during this time period and then calculated the firing frequency by dividing the count by the appropriate time interval in each trial. We did the same trial-by-trial analysis for a time window of 500 ms preceding the GO signal. To qualify as a reach-related neuron, the mean firing frequency in the period after the GO cue until the end of the arm movement had to be significantly higher than the mean firing frequency in the preceding time period (Whitney-Mann, P < 0.01). We also determined the mean rectified EMG during this period as a measure of muscular activity.
We computed both a two-way ANOVA (P < 0.01) and a gaze-dependency index (GD) to quantify the extent to which a given cell operates in a gaze-centered or in a gaze-independent reference frame. The basic rationale of the comparison was the same for both measures. We compared two arm movements starting from and ending at identical positions in external space. What differed in the two cases was the direction of gaze with respect to the target. In one case (measured during the FR task), the gaze was directed away from the reach target, whereas in the other case (measured in the SR task), the gaze was aligned on the target. Because the two compared arm movements were identical, any systematic change in reach-related cell activity should be a result of the difference between target and gaze axis in the two cases. As mentioned before monkeys C and S were tested with slightly different target displays. The display for monkey C used only one fixation point and thus did not provide us with comparable mappings from different fixation positions as in monkey S. Nevertheless for both displays, we had data recorded during identical reach movements while the monkey's gaze axis was aligned with the reach target (SR task) as well as while it was directed away from the reach target (FR task).
The ANOVA was computed to test if there was a systematic influence of gaze across the different arm movements. The data for the ANOVA were the average neuronal firing frequency from the GO cue to the end of the arm movement in the individual trials. The factors for the ANOVA were the craniocentric target position (which is related to the arm reaching movement toward a certain position in the workspace) and gaze direction (either pointing to the target or to the central fixation light).
The GD was computed to quantify the amount of modulation of the
neuronal discharge during the reach caused by the gaze shift. GD was
calculated in the following way. First, we determined the target with
the maximal reach activity (the mean of the firing frequency from the
GO cue to the end of the arm movement over the individual
trials) of the neuron in the FR task condition. We took this target
location to be the preferred gaze-target vector (GTVp). Second, we determined the neuron's
discharge while the monkey reached to the identical target on the
screen, but this time in the SR task, in which the monkey fixated the
target before and during the reach. This gaze orientation resulted in a
gaze-target vector that was zero (GTV0). We
compared the two situations by calculating the GD index
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To reconstruct the spatial relationship of the reach neurons among each
other, we used the visual receptive field, measured in the same
penetration during the passage of the superficial layers, to estimate
the position of the neurons on a reduced SC map. We used the equations
of Ottes et al. (1986) to relate collicular and
retinotopic coordinates.
To compare the average discharge modulation in the two reach cell populations (gaze-dependent and -independent), we computed histograms of their population activity during the FR task. To eliminate the trial-by-trial variation in the duration of different behavioral elements in the FR task, we divided these elements into a fixed number of bins that remained the same in each trial. The FR task was divided into five successive behavioral elements. First, the "waiting phase" (50 bins) lasted from fixation onset until target onset. Second, the "delay phase" (60 bins) lasted from target onset until the acoustic GO signal was given. Third, the "reaction time" (20 bins) lasted from the GO signal to onset of the arm movement. Fourth, the "movement phase" (10 bins) lasted from onset of the movement until the hand made contact with the target. Fifth, the "target hold phase" (35 bins) finally lasted from contact with the target until its release at the beginning of the return movement. The number of bins for each phase was chosen in such a way that one bin accounted on average for ~20 ms. The actual time represented by such a bin could vary with the duration of the respective phase in the trials. Therefore the activity in a certain bin does not represent the mean activity in real time relative to a trigger point but rather the mean activity at a certain fraction of the respective behavioral element. For example the first bin of the MP shows the average discharge during the first 10% of the arm movement. Therefore we called the resulting histograms "relative time histogram" (RTH).
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RESULTS |
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Classification of neurons
In two monkeys, we recorded 331 neurons in the SC and the underlying mesencephalic reticular formation (MRF) over a depth from 1 to 6.5 mm below the SC surface. These neurons were classified with respect to the relationship of their discharge to the visual cues and the eye and arm movements as visual (V), saccade-related (S), fixation (F) and reach-related (R) neuron (see Table 1).
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Sixty-five neurons with reach-related activity provided sufficient data for quantitative analysis. Four examples of them are shown in Figs. 3 and 4. All of them showed a burst of activity at the time of the arm movement. However, the start and end of this burst varied in individual cells. It began at some point in the interval between the GO cue (Fig. 3A) and the onset of the reaching movement (e.g., Fig. 4A). The burst ended either while the movement was still ongoing (Fig. 3A) or, more often, when the monkey had grasped the target handle (Fig. 4B). Some neurons displayed also an additional modulation in the delay interval preceding the arm movement. This delay modulation was often more pronounced in the FR task and could be either an inhibition (Figs. 3A and 4A) or a ramp-like increase (Fig. 3B) of the discharge.
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The great majority of the reach-related cells (86.1%) showed no
modulation related to saccades. This is in accordance with earlier
findings by Werner et al. (1997b).
Besides many similarities, a comparison of the discharge modulation in the SR and the FR tasks also revealed a clear difference between two different types of reach-related cells. On the one hand, there were cells like the ones shown in Fig. 3 that show no or only slight differences in their discharge during the actual arm movement in the two tasks. Because the arm movement was the same in the two cases, this finding was not unexpected. On the other hand, we found also cells like the ones shown in Fig. 4 the discharge of which was dramatically different depending on which task the monkey performed. Because the arm movements were identical, this difference had to be related to the difference in gaze angle.
To determine quantitatively this effect of the gaze-related target coordinates on the reach activity, we computed a GD index. This index equals ±1 if the activity occurred only during one of the two compared arm movements and therefore depended maximally on the direction of gaze. If, on the other hand, the index equals 0, the activity is not modulated by gaze angle and therefore seems independent of it. In addition to this index we computed also a two-factor ANOVA (craniocentric target position, gaze direction, P < 0.01).
The monkeys might perform the arm movements in a slightly different manner in the SR and the FR task. This could result in different activity patterns of the musculature in the two movements compared. To estimate the amount of difference, we also computed the GD values of the rectified and averaged EMGs from representative shoulder and arm muscles made simultaneously with the neuron recordings. The GD distribution of these muscles gives an estimate of the amount of change that the gaze shift produced in the skeletomotor system. A comparison of muscle activity from the deltoideus anterior (Adl) during arm movements toward targets at identical locations with respect to the body but with different coordinates with respect to gaze direction (e.g., toward target 5 while looking at fixation point F1, F2, and F3, respectively) is shown in Fig. 5. Clearly, the EMG patterns display almost the same amplitude and shape during identical reach movements with different gaze angles.
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In Fig. 6 the GD distributions of the muscles and the neurons are shown for comparison. Figure 6A gives the mean GD values of the 13 muscles. The unimodal distribution clearly is centered on zero, and values do not exceed ±0.3. In the ANOVA none of the muscles showed an effect of the gaze angle during reaching. Figure 6B shows the GD values of the 65 reach neurons. The units for which the ANOVA (P < 0.01) showed a significant influence of gaze angle are shown in black. In 27 cells the GD falls outside the range of the muscle modulation and exceeds ±0.3, corresponding to twice the activity in case of preferred as compared with nonpreferred gaze-related target coordinates. All of these cells with the exception of two near to the 0.3 level are influenced significantly by gaze angle. We called the 25 (38.5%) cells that fulfill both criteria (ANOVA P < 0.01; GD > ±0.3) "gaze-related reach neurons." The GD values of the rest of the reach-related neurons (n = 40, 62.5%) fall into the same range as the GD of the muscles, indicating that their reach activity is independent of retinocentric or eye-position variables. Although some of them showed a significant gaze influence in the ANOVA, we excluded them from the group of the gaze-related reach neurons because they did not fulfill the second criteria (GD > ±0.3). We called this second type of cells "gaze-independent reach neurons."
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Characteristics of the gaze-related reach neurons
The typical activity pattern of a gaze-related reach neuron both in the SR and FR task is shown in Figs. 7 and 8. In Fig. 7 the discharge of this sample neuron is presented in relation to onset of arm movements in the FR task while the monkey uses either the ipsilateral or the contralateral arm. The 12 histograms on the right were compiled in sets of four according to the arrangement of four reach targets around each of the three fixation points (+). All movements were made with the contralateral (here the right) arm. They started with the hand approximately at waist level and were directed to one of the eight targets (1-8), positioned on a frontal screen as outlined in the sketch in the lower right corner of Fig. 7. Activation was observed only when the arm was directed to a target at the lower right with respect to the fixation point. This occurred with targets 5, 6 and 8. However, if the same arm movement (e.g., to target 5) was performed with eye positions that shift the target location with respect to the gaze axis, i.e., to the upper right or lower left the neuron displayed no reach-related activity. The neuron was also not active during reaching when the same eight targets were fixated in the SR task, as illustrated in Fig. 8.
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Even for the same target location with respect to the gaze direction (see Fig. 7, targets 5 (F1), 6 (F2), and 8 (F3)) the cell discharge is different for the three different orbital positions of the eyes during the reach. This eye-position effect occurred across the tested oculomotor range for all gaze-related reach cells. We did not perform a quantitative description of these gain fields because we felt that three different gaze positions did not allow such a treatment of the data.
All these experiments demonstrate that the reach-related activity of this neuron is locked to a gaze-related coordinate system and cannot be described in an allocentric or body-centered reference frame. Nevertheless, its activity is in close temporal relationship to the arm movement, preceding the onset of movement by ~200 ms. We called the area of target coordinates in a gaze-related frame of reference that is accompanied by neuronal activity the "reach movement field" (RMF). It is important to note that both the specific path of the arm movement and the muscle pattern that is necessary for its realization are of no consequence for the neuron's discharge. Two neurons of the 25 gaze-related neurons also produced saccade-related bursts, but we found no relationship between these components and particular characteristics of the reach-related activity.
Activity of the gaze-related reach neurons during reaching with the contra- or ipsilateral arm
To see whether the reach neurons show a preference for the use of the arm contra- or ipsilateral to the recorded SC neuron, we let the monkey perform the FR task with either arm. Because of workspace constraints, we could compare only the movements that were in a medial position with respect to the body axis while the monkey fixated the fixation points F1 and F3. The fixation point F2 was on a more lateral position and included movement targets that could not be reached with the left arm. In Fig. 7A, the activity of the same cell that was discussed in the preceding text in the case of reaching with the contralateral (right) arm is shown also during use of the ipsilateral (left) arm. A comparison of the neuronal discharge histograms reveals that the neuron displays the same pattern of activity with an identical spatial tuning and almost the same amount of spikes irrespective of which arm is used although anatomically different muscles execute the reach movements. A further demonstration of the similarity of the activity level during reaches into the RMFs with the ipsilateral or contralateral arm is shown for eight neurons in Fig. 9. Each dot shows the mean neuronal activity for one of the eight neurons while the monkey reached to the "preferred" targets surrounding the fixation points F1 and F3 (see Fig. 7). The plot basically confirms the points taken from the example shown in Fig. 7. Only in one of the eight neurons was the difference between the activity during the reach with the contra- or ipsilateral arm significant (triangle pointing down; t-test Bonferroni corrected: P < 0.05). Otherwise there are just as many values on either side of the unity slope line. All in all, a population of gaze-related reach neurons in the colliculus becomes activated during a goal-directed reach largely independent of the muscles or arm involved in the reach.
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RMFs
We found that the RMFs of gaze-related reach neurons differed with
respect to their peripheral borders. In six neurons, the RMFs were
mapped partially by presenting reach targets further and further away
from the preferred retinal target position. Figure 10 shows two examples of these cells.
Neuronal discharge of the cells is shown while the monkey fixated a
certain position on the screen (the cross) and reached to a number of
targets (indicated by position of the histograms). The amplitude of
reach activity increased when the monkey was reaching to more
peripheral targets in the cell presented in Fig. 10. This suggests that
its RMF occupies a large area of the visual field and may possibly have
no clear peripheral border at all. Such patterns of neuronal activation were seen in four of the six neurons tested. The other two cells allowed no clear conclusion due to the limited number of tested locations. In addition to these cells, we also recorded three neurons
with a GD value more than 0.3 (Fig. 6B). This GD index resulted from a strong activation of the neurons in the SR task coupled
with a weak discharge during reaching to targets falling outside the
fovea. An example of these cells is shown in Fig. 11. In Fig. 11A, the
neuronal activity during reaching to the four targets surrounding the
F1 fixation point in the FR task is displayed. In Fig. 11B,
we see the neuronal discharge while the monkey reached to the same
targets during the SR task. Obviously, the cell is much more and always
activated when the target falls on the gaze axis. Another observation
is the identical amplitude of the discharge for all spatial positions
in the SR task. Because the arm movements are the same in the two
tasks, once again the difference in response must be due to the
gaze-related target position. These neurons seem to have RMFs that are
positioned on the fovea and peripheral borders of which lie somewhere
between the fovea and the targets with an eccentricity of 15°.
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Distribution of RMF orientation on the SC
For the 25 gaze-related neurons (ANOVA P < 0.01; GD > ±0.3), the direction and spatial selectivity of the RMFs was assessed quantitatively by constructing the vector sum of the normalized neuronal activity during reaching to each of the four targets. The orientation of the resulting vector pointed toward the RMF of the cell. Vectors pointing into the contralateral hemisphere were indicated by a rightward orientation. The length of the vector increases with a sharper spatial selectivity of the cell.
To test whether there is a map-like arrangement of the RMFs of
gaze-related neurons parallel to the collicular surface, we plotted
these vectors on the simplified visual map of the SC (see Fig.
12). To construct this map, we used the
equations of Ottes et al. (1986) to plot the
anterior-posterior and mediolateral position of a reach neuron in the
SC according to the coordinates of the visual receptive field measured
in the same penetration during the passage of the superficial layers.
The reach cell's location according to this visual map serves as the
origin of the respective RMF vector. The RMFs of the gaze-related reach neurons could be directed either into the ipsi- or the contralateral hemifield, i.e., the preferred reach target location could be in the
entire visual field and was not restricted to the contralateral hemifield; this is in sharp contrast to the organization of the visual
map and saccadic movement fields. In addition, gaze-related reach cells
recorded in a single penetration next to each other repeatedly showed
clearly different RMF positions. But a closer inspection of Fig. 12
might reveal a weak organizing principle. The subpopulation that was
recorded in the medial part of the colliculus corresponding to the
upper visual field consisted mostly (8/13) of cells with RMFs also
oriented upward. Correspondingly, the lateral part of the SC was
dominated by gaze-related reach neurons with downward oriented RMFs
(8/12). All seven reach cells recorded within 5° eccentricity to the
foveal representation had RMFs directed into the ipsilateral hemifield,
whereas 13 of the 18 reach cells recorded in penetrations with visual
fields with >5° eccentricities had RMFs directed into the
contralateral hemifield.
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Gaze-independent neurons
The other group of units analyzed in detail consisted of 40 neurons that showed no or only a weak dependence of their discharge on the orientation of the gaze axis (ANOVA P > 0.01 or GD < ±0.3). An example of such a gaze-independent neuron is given in Fig. 13. The pattern of discharge is the same in the fixation and saccade-reach task, although the neuron shows a modulation of its activity in relation to the four target positions.
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We computed the orientation of the RMF vectors in the same way as for the gaze-related neurons and plotted them on the oculomotor map of the SC (Fig. 14). This reveals two points. First, the gaze-independent cells show an even less ordered distribution across the SC compared with the other group of reach cells. Second, the tuning sharpness as visualized by the vector length is much weaker than the corresponding values of the gaze-related neurons.
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Discharge dynamics of gaze-related and -independent reach neurons
To compare the discharge dynamics and directional modulation depth of the two reach-related populations, we compiled RTHs of the activity of the reach neurons during the FR task for the gaze-dependent and the -independent populations separately. First we computed for each neuron a relative time histogram of the averaged activity for all recorded arm movements toward a certain target in the FR task. Then for each neuron from its pool of histograms we chose the two associated with the maximal and minimal response. Next we calculated separate population histograms for the maximal and minimal activities.
The gaze-independent neurons (Fig. 15A) show on average a smooth increase of their discharge, starting in the delay period (after target on) before the GO cue is given. At this moment the monkey has all the information that is needed to perform the arm movement and is merely waiting for the start signal. Thus the activity during this time probably reflects the expectation and preparation to execute the planned movement in the near future. Examples of gaze-independent neurons with anticipatory activity components can be seen in Figs. 3B and 13. The discharge dynamics in the case of maximal and minimal activity are the same. The peak in the maximal activity gets about twice as high as the peak in the minimal activity.
The picture is very different for the gaze-related neurons (Fig. 15B). First, the maximal discharge amplitude of the gaze-related cells is nearly twice as high as the one of the gaze-independent cells (153.5 vs. 81.9 imp/s). We found no gaze-related neurons with delay activity preceding the command to reach to the target. The rise of the discharge begins only after the GO cue is given. At this point, the slope of the rise is comparable with that in the gaze-independent neurons. With movement onset, the slope dramatically increases, which leads to a brisk burst of discharge, lasting until the arm makes contact with the target. In contrast to the course of the maximal discharge, the minimal activity is nearly negligible over the equivalent time span.
Depth of gaze-related and -independent reach neurons below the surface of the colliculus
The depth distribution of the two types of reach-related neurons
is shown in Fig. 16. For comparison, the depth distribution of the saccade-related neurons as recorded in our experiments also is
shown. We could not reconstruct the position of single neurons in the
histological sections of the SC, because after 1.5 (monkey
C) and 1 yr (monkey S) of recording it was not possible anymore to identify single penetration tracks. However, in monkey C we made lesions at the position of two gaze-independent reach neurons during the last week of recording. The depth below the surface
of the SC of both lesions matched very well with the depth recorded by
our microdrive. Further histological verifications of reach cells in
the SC are given in a previous publication (Werner et al.
1997b). We recorded the gaze-related reach neurons in the SC at
depths of 0.9-3.6 mm with a median of 2.02 mm (Fig.
16B). They mostly overlap with saccade-related
burst neurons recorded in the same penetrations over a range of
0.8-3.0 mm (plus 2 units at 5 mm) with a median depth of 1.55 mm (Fig.
16A). Thus the gaze-related reach neurons seem to lie also
in the intermediate layers interspersed with saccade-related neurons.
By contrast, most of the gaze-independent reach neurons were found in a
range of 1.3-6.5 mm below the SC surface with a median depth of 4.01 mm (Fig. 16C). If both cell types were found in individual
penetrations, gaze-independent cells were mostly found below
gaze-dependent cells.
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DISCUSSION |
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This study demonstrates that the reach-related neurons in the SC
and underlying MRF are composed of at least two functionally separable
populations. Gaze-related reach neurons are located in the SC and
overlap mainly with the depth distribution of the saccade-related
neurons recorded in the same study. Gaze-independent reach neurons
could be found in the SC, but a great number of them were located in
the underlying MRF. The median depth of this population (4.01 mm) is 2 mm deeper than the median depth of gaze-related reach cells (2.02 mm).
These anatomically differently located two populations differ also in
their frame of reference, their tuning strength, and the dynamic of
their discharge modulation during the task. In another study, using
only the SR task, arm-movement-related neurons were reported to be
distributed between 0.7 and 6 mm below the SC surface with a median of
3.9 mm (Werner et al. 1997b), which is indistinguishable
from our present result for the gaze-independent reach cells. In Werner
et al.'s studies gaze-related neurons could not be identified because
the animals were not trained to perform the FR task. Neither group of
neurons shows a topographically ordered anatomic distribution matching
the well-known visual or oculomotor maps in the SC (see Figs. 12 and
14).
The gaze-related reach neurons seem to be organized in a reference
frame centered on the gaze axis. The discharge of the gaze-independent neurons might conform to a shoulder and arm-centered frame of reference. In this case, the strength of neuronal discharge would depend on the arm used to reach to the target. In this study, we did
not test the activity of the gaze-independent neurons while the monkey
was using his ipsilateral arm. However, Werner et al. (1997a) present such data in their Fig. 8 in support of a
shoulder- or arm-centered reference frame. All of the 26 reach neurons
they analyzed in their study showed a weaker activity (sometimes a decrease by 80%) when the monkey used its ipsilateral arm.
Function of the gaze-related reach neurons
The experimental setup we used in this study allowed us only a
very broad mapping of the RMF structure of the gaze-related reach
neurons. The distinction between neurons with closed or open RMFs
therefore remains of a tentative nature. Nevertheless the gaze-related
SC cells have spatially selective RMFs. For a given gaze position, this
population of neurons would reliably signal reach target positions
relative to the fovea. The motor system of primates could use this
information under certain behavioral constraints, e.g., when a monkey,
looking at a distant piece of food, at the same time is reaching out to
climb up nearby branches or when one reaches for a pencil while reading
a text. The main arguments against this interpretation result from the
temporal pattern of activity of the gaze-related reach neurons. First, the activity of all these neurons begins to rise only with the GO cue and shows another sharp burst-like rise shortly
before the arm movement onset that lasts over the movement time. This is not in agreement with the hypothesis that these neurons code the
target location or the intention to move to the target because in that
case these signals should be generated from shortly after the target
onset until the execution of the movement. Neuronal activity in the
parietal cortex indeed shows a continuous discharge starting with
target onset in an instructed delay phase preceding a movement
(Batista et al. 1999; Bushnell et al.
1981
; Paré and Wurtz 1997
; Snyder
et al. 1998
). Second, the population activity of the
gaze-independent reach neurons begins to rise before that of the
gaze-related neurons. This is not in accordance at least with a simple
and straightforward interpretation of gaze-related neurons carrying a
spatial signal representing an earlier level in the visuomotor
transformation than the gaze-independent neurons. Both facts argue
rather in favor of the hypothesis that the gaze-related reach discharge
is related to the time of actual movement execution.
Under natural reaching conditions, the gaze shift starts much sooner
than the arm because of the different inertia of the eye (Biguer
et al. 1982). Therefore the gaze axis already is oriented toward the reach target when the arm movement starts. A mismatch should
be corrected quickly. There is good psychophysical evidence for the
existence of a fast correcting mechanism during goal-directed arm
movements in humans (Biguer et al. 1982
; Goodale
et al. 1986
; Prablanc and Martin 1992
). If
during pointing, in some trials, the position of the target was
suddenly shifted while the saccade toward the target reached its peak
acceleration and the subjects just started the arm movement, they
responded with a catch-up saccade directed toward the new target
position. Because of saccadic suppression, the subjects were not aware
of the perturbation. Nevertheless they also changed their ongoing arm
trajectory so that the arm reach ended at the new location. This
compensation took place with a latency of 150 ms. With a similar task,
Alstermark et al. (1990)
demonstrated for cats the same
ability to switch on-line from one target to another with a latency of
80-120 ms. Transsection of the cortico- and rubro-spinal tract did not
alter this ability. Interruption of the tecto-spinal and
tecto-reticulo-spinal tracts on the other hand lead to a prolongation
of the switch latency and an initial ataxia of the forelimb
(Alstermark et al. 1987
, 1990
).
The SC might be the neural substrate involved in this automatic on-line
correction mechanism for reaching movements also in primates. The
activity of the gaze-related reach neurons signals the amplitude and
direction of the difference between the targets of the two control
systems for gaze and reach. This measure of gaze-arm-orientation
mismatch provides a motor-error signal about the relative change in the
arm movement trajectory that is necessary to get to the fixated target.
But there are also situations requiring the dissociation of the targets
for attention, gaze, and arm movement. An example of such a situation
is the FR task used in our study. The premotor cortex (PM) is discussed
for its role in mediating arbitrary visuomotor transformations
(Wise et al. 1997). To do this, PM and more generally
also other parts of the frontal cortex have to learn the arbitrary
mapping rules and execute them if needed. But in such a situation the
cortex also would have to cancel the motor control commands coming from
other parts of the brain that result from the standard visuomotor
mapping rules. Therefore in a normal primate the cortex controls the SC
and the rest of the brain stem (Dias et al. 1995
;
Pierrot-Deseilligny et al. 1991
; Schlag-Rey et
al. 1992
; Segraves and Goldberg 1987
). In this
context, it is interesting to note the results of the ablation of PM,
frontal eye field (FEF), and supplementary eye field (SEF) in
the rhesus monkey (Moll and Kuypers 1977
). This lesion
leaves the ability for standard reaching intact but specifically results in an inability to unlock the targets for the eyes and the hand
in a test of detour reaching. This compulsion of the arm to reach
straight to a fixated visual target is exactly what is to be expected
if the proposed collicular servomechanism dictates the reach because
the ablated cortical areas cannot exert their inhibitory control on the
SC any more.
Visual attention
Primates are able to attend to peripheral objects while
maintaining eye fixation, i.e., without an overt gaze shift to the attended location (Corbetta et al. 1998). Such a covert
shift of spatial attention leads to activity changes in build-up
neurons in the SC, although no saccade will be executed (Kustov
and Robinson 1996
). A redirection of attention without a
saccade is also necessary during the performance of the FR task. One
might ask if the gaze-related reach activity really was related to the
arm movement or whether it is just the result of an intended but not
executed gaze shift or shift of attention to the location of the reach
target in the FR task. A couple of reasons make the covert gaze shift
hypothesis very unlikely. Only a minority of gaze-related neurons
(2/25) is active before and during saccades without arm movement. The activity of almost all of the reach neurons starts before arm movement
onset and not with target onset (see Fig. 15).
Finally the RMF of nearly half of the gaze-related
reach neurons is directed into the ipsilateral visual hemifield. This
activity could hardly be interpreted as subliminal oculomotor activity
in the SC because to our knowledge saccade-related neurons whose
saccadic movement field is oriented in such a way have never been
described in three decades of extensive research in this structure. It
is unclear, however, whether a system responsible for the shift of
visual attention has to conform to the saccadic system or can be active in a broader range of circumstances. We could imagine that in our FR
task activity of gaze-dependent reach cells could be used to shift
spatial attention to where the hand is going only with the onset of the
actual execution of the reach.
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Does the activity of gaze-dependent reach neurons represent an efference copy? This possibility is difficult to be ruled out at any level in the sensorimotor system. The SC neurons are only active if there is a certain spatial relationship between gaze axis and reach target. This fact argues against the interpretation as efference copy at least in its most simple version. A copy of the motor command should be present whenever there is a certain arm movement.
Comparison with other studies
Reach-related neurons that operate in a gaze-centered coordinate
system exist both in the parietal and frontal cortex. Recently an area
in the posterior parietal cortex (PPC) overlapping with areas V6A and
medial intraparietal area has been described to contain neurons
specialized for the planning of reach movements (Snyder et al.
1998). It has been found that the neurons in this area
code in eye-centered coordinates (Batista et al. 1999
).
These cells show a remarkable similarity with the gaze-related reach neurons presented in this study except for the timing of their neuronal
discharge. Whereas the onset of activity of most collicular cells is
only with the beginning of motor execution, the parietal cells begin to
discharge shortly after the target presentation. This suggests a
difference in function. The posterior parietal cortex probably is
involved in early stages of motor planing and attentional processes
related to target selection. It also might supply the superior
colliculus with information about the position of the reach target with
respect to the gaze axis. Desmurget et al. (1999)
showed
in humans that transcranial magnetic stimulation of the PPC disrupted
path correction of pointing movements in the dark to visual targets
that had been moved during saccadic eye movements. They interpreted
their results as evidence for a role of the PPC in a feedback loop that
adjusts on-line the muscle activation pattern. The PPC might in part
put the gaze-related reach neurons of the SC in the loop to influence
the motor machinery. The other important target of the parietal cortex
is the frontal cortex, especially the PM. This cortical area is
involved in the planing and execution of limb movements
(Boussaoud 1995
; Wise et al. 1997
) and
projects to the motor cortex, to the basal ganglia as well as directly
to the spinal cord (He et al. 1993
). The gaze-modulated neurons in PMv described by Mushiake et al. (1997)
show
the most compelling similarities to the gaze-dependent reach neurons in the SC. Like their collicular counterparts, the PMv neurons operate in
a gaze-related coordinate frame, and they are active in relation to the
execution of reaching movements. Both the posterior parietal cortex and
the mentioned frontal areas (PM, SEF, FEF) project to the superior
colliculus and the underlying mesencephalic reticular formation
(Fries 1984
, 1985
; Huerta and Kaas 1990
).
Therefore these cortical areas together with the midbrain might form a
closely integrated network devoted to the coordination of eye and arm movements.
Conclusions
Besides the well-known sensorimotor neurons that shift the gaze
toward a target (Munoz and Wurtz 1995), two new
populations of neurons have been described in this paper that are
active before and during arm movements. The first population located
exclusively in the SC operates in a gaze-related coordinate system.
These cells might carry signals representing the goal for the arm
movement in a gaze-centered reference frame or they might represent a
motor error signal used by a servosystem for steering of the hand
toward the point in space the monkey is fixating. In either case, their reference system is suited ideally to use the sensory information provided by visual, auditory, and somatosensory cells in the SC, all
operating also in a gaze-related reference frame (Jay and Sparks
1984
; Mays and Sparks 1980
). The discharge of
the second population that is located deeper in the SC and in the
underlying MRF is related more directly to the actual movement and
operates in a gaze-independent reference frame.
At the moment no direct evidence exists about the anatomic connection
of the two classes of reach cells. The majority of descending tectofugal axons arise from collicular laminae that lie ventral to the
stratum opticum. Such descending axons can be grouped into two major
bundles or tracts, i.e., the ipsilateral tectopontine-tectobulbar tract
and the crossed tectospinal tract (or the predorsal bundle). The
ipsilateral pathway projects among other targets to the mesencephalic reticular formation and the cuneiform nucleus (Harting
1977). The tectospinal tract belongs together with the
reticulospinal tract to the ventromedial descending brain stem system
(Lawrence and Kuypers 1968
). The combined projections of
this system terminate within parts of the spinal cord that innervate
axial and proximal arm muscles. The discharge of some of the
gaze-independent reach neurons is correlated highly with the activity
of muscles from the shoulder girdle and the upper arm (Stuphorn
et al. 1999
; Werner et al. 1997a
). Others are
related to the end point or the direction of the arm movement
(Stuphorn et al. 1995
). These findings fit well to a
picture of the SC as a brain structure mainly involved with the spatial
orientation of different body parts like reaching toward a point in
external space but not with the fine control of the hand and fingers
necessary for grasping and manipulating objects. The connection between
SC and spinal cord in primates is probably not via direct projections
to a C3-C4 propriospinal system (Maier et al. 1998
). Instead it might be an
indirect connection via arm-reaching related neurons further caudal in
the brain stem (Ruffo and Buford 1997
).
Another possible target for the reach-related neurons in the colliculus
might be the cerebellum via the ipsilateral tectopontine projection. It
recently has been shown that Purkinje cells encode both destination and
error (i.e., deviation of the final arm position from the intended one)
of arm movements (Kitazawa et al. 1998). This
information that is represented in the discharge of collicular reach
neurons could possibly be of great importance for the cerebellum to
contribute to the long-term improvement of movements (Gilbert and Thach 1977
; Houk et al. 1996
). In any case,
our results further add to the hypothesis that neurons in the SC and
the underlying MRF are integrated in the neuronal network controlling
arm movements in primates.
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ACKNOWLEDGMENTS |
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We thank Dr. M. Pekel for the computer program and Dr. C. Distler for surgery.
This work was supported by the German Science Foundation (Deutsche Forschungsgemeinschaft Graduate Program Grant KOGNET GRK 81/2-1 and Research Grants Ba 841/2-1 and Ho 450/24-2).
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FOOTNOTES |
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Address for reprint requests: K.-P. Hoffmann, Lehrstuhl für Allgemeine Zoologie und Neurobiologie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.
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 4 January 1999; accepted in final form 13 October 1999.
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REFERENCES |
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