Department of Neuroscience and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
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ABSTRACT |
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Nakamura, Kae and Carol L. Colby. Visual, Saccade-Related, and Cognitive Activation of Single Neurons in Monkey Extrastriate Area V3A. J. Neurophysiol. 84: 677-692, 2000. Area V3A is an extrastriate visual area that provides a major input to parietal cortex. To identify the sensory, saccade-related, and cognitive signals carried by V3A neurons, we recorded from single units in alert monkeys during performance of fixation and memory guided saccade tasks. We found that visual responses to stationary stimuli in area V3A were affected by the behavioral relevance of the stimulus. The amplitude of the visual response differed between the memory-guided saccade task, in which the monkey had to use the information provided by the stimulus to guide its behavior, and the fixation task. For 18% (29/163) of V3A neurons, the response was significantly enhanced in the memory-guided saccade task as compared with that in the fixation task. For 8% (13/163) of V3A neurons, the amplitude of response in the memory-guided saccade task was significantly suppressed. We also observed task-related modulation of activity prior to stimulus onset. Among the V3A neurons (37/163) that showed significant differences between tasks in prestimulus activity, the majority (89%; 33/37) showed greater prestimulus activity in the memory-guided saccade task. Task-related increases in prestimulus activity in the memory-guided saccade task were not always matched by increases in the sensory response, indicating that visual responses and prestimulus activity can be modulated independently. Activity in the memory period was suppressed compared with prestimulus activity for 83% (49/59) of the V3A neurons that showed a significant difference in activity (59/197) between these two epochs. For some neurons, memory-period activity dropped even below the baseline level in the fixation task, indicating that there may be an active suppression mechanism. Many V3A neurons (75%, 148/197) also had activity in the saccade epoch. This activity was most prominent immediately after the saccade. Postsaccadic activity was observed even when testing was carried out in total darkness, indicating that this activity reflects, at least in part, extraretinal signals and is not simply a response to visual reafference. These results indicate that several kinds of signals are carried by single neurons in extrastriate area V3A. Moreover, activity in V3A is subject to modulation by extraretinal factors, including attention, anticipation, memory, and saccadic eye movements.
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INTRODUCTION |
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Area V3A is an important link
between several extrastriate areas and parietal cortex (for review, see
Beck and Kaas 1999; Felleman and Van Essen
1991
). It receives substantial inputs from earlier extrastriate
areas such as V2 (Gattass et al. 1997
) and V3
(Felleman et al. 1997
), as well as very sparse direct
connections from V1 (Van Essen et al. 1986
; Zeki
1978a
, 1980
). Area V3A in turn provides a major input to the
lateral intraparietal area (LIP) and receives reciprocal projections
from it (Andersen et al. 1990a
; Baizer et
al. 1991
; Blatt et al. 1990
; Cavada and
Goldman-Rakic 1989
; Morel and Bullier 1990
). It
is also strongly linked with several dorsal stream areas, including the
dorsal prelunate area (Andersen et al. 1990a
), the
middle temporal area, MT (Ungerleider and Desimone
1986
), the medial superior temporal area, MST (Boussaoud et al. 1990
), the fundus of the superior temporal visual area, FST (Boussaoud et al. 1990
), and the parieto-occipital
area, PO (Colby et al. 1988
). Area V3A is also
reciprocally connected to the frontal eye field (Schall et al.
1995
; Stanton et al. 1995
) and ventral stream
areas such as the ventral posterior area, VP (Felleman et al.
1997
), V4 (Felleman and Van Essen 1983
), and TEO
(Morel and Bullier 1990
; Webster et al.
1994
).
Since area V3A was discovered (Van Essen and Zeki 1978;
Zeki 1978b
,c
), there have been several reports on its
response properties. Many V3A neurons are orientation selective and
sensitive to binocular disparity (Zeki 1978c
). They are
also motion sensitive and direction selective, although by comparison
with area V3 direction selectivity is much less prevalent
(Felleman and Van Essen 1987
; Galletti et al.
1990
; Gaska et al. 1988
; Zeki
1978b
,c
).
The important early studies of Galletti and colleagues in the alert
monkey showed that neuronal activity in area V3A reflects both retinal
input and eye position (Galletti and Battaglini 1989). They found that the visual response was modulated by the position of
the eye in the orbit for about half of the population. Many V3A neurons
also discriminate between real motion of a stimulus and equivalent
motion of a visual stimulus in the receptive field produced by eye
movement (Galletti et al. 1990
).
The aim of the present study was to characterize the response
properties of area V3A neurons in awake, behaving monkeys in tasks
previously used in area LIP (Barash et al. 1991a,b
;
Colby et al. 1996
; Goldberg et al. 1990
).
We found that V3A neurons carry memory and saccade-related signals as
well as visual information. Moreover, we found that baseline activity
is subject to modulation by expectancy, and visual activity is
modulated by attention.
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METHODS |
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Animal preparation
Two rhesus monkeys (Macaca mulatta) were used
in this study. They were surgically prepared under general anesthesia
(induced with ketamine and maintained with isoflurane) for chronic
neurophysiological recording by implantation of head-holding devices
and recording chambers through which electrodes could be introduced
into the cerebral cortex. To monitor eye position, we implanted scleral search coils (Judge et al. 1980). Recording chambers
(1.8 cm diam) were placed flat against the skull, centered at
stereotaxic coordinates AP
25 and L 15 mm. We used structural
magnetic resonance (MR) images taken prior to surgery to determine
these coordinates. Structural MR images were also obtained after the
placement of each chamber to determine the location of specific
structures, such as the annectent gyrus, relative to the coordinates of
the recording chamber.
During the recording period, the animals' weight and health status were carefully monitored. Fluid supplements were given as needed. Recording chambers were flushed with saline before and after each recording session. When necessary, the exposed dura in the recording chamber was surgically debrided under ketamine anesthesia. All experimental protocols were approved by the University of Pittsburgh Institutional Animal Care and Use Committee and were certified to be in compliance with the guidelines set forth in the Public Health Service Guide for the Care and Use of Laboratory Animals.
Structural MRI
In both monkeys, the extent and location of the recording zone were verified by structural MR images (Fig. 1). To locate target brain structures relative to the recording chamber, we used a cylindrical device that allowed us to determine the plane and trajectory of the electrode penetrations. The cylinder had four hollow tubes filled with providone-iodine ointment (Betadine) so as to be visible in the MR image. The cylinder was placed in the recording chamber and rotated so that it matched the orientation of the recording grid. The four hollow tubes were arranged in a square, and the plane between each lateral pair of tubes matched the plane of the recording penetrations. The slice prescription for obtaining MR images was determined by capturing a pair of tubes in a single slice (Fig. 1A). For each recording chamber, we obtained 24 images spaced 1.5 mm apart.
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Identification of recording sites
Area V3A occupies the posterior part of the annectent gyrus, buried in the depth of the lunate sulcus. In all four hemispheres, we used a combination of grid site and recording depth to reconstruct the locations of recording sites on drawings from the MR images. We found that the locations of brain structures (gray matter, white matter, and the lunate sulcus) as indicated by recording depth corresponded very closely to the MR images. To confirm that a given neuron was in area V3A, many neighboring penetrations had to be taken into account, using the shifts of receptive field location along each penetration and grid coordinates. Therefore before starting the main study, we mapped the location and size of receptive fields of cells in area V3A and adjacent visual areas. This procedure is described in detail in RESULTS.
Physiological methods
Recordings were made with tungsten microelectrodes (Frederick
Haer) introduced through stainless steel guide tubes placed nearly but
not quite through the dura, which in turn were stabilized by a nylon
grid held rigidly in the recording cylinder (Crist et al.
1988). The grid system served as a guide to produce parallel penetrations with a resolution of 0.5 mm.
During recording sessions the monkey sat with head fixed in a primate chair in a darkened room facing a tangent screen 27 cm away, subtending 100° horizontally and 76° vertically. Visual stimuli were computer generated and back-projected onto the screen. Behavioral monitoring, eye position, and unit sampling were performed by computer. Action potentials were amplified, filtered with a band-pass of 500 Hz to 5 kHz, and digitally sampled using template matching at 20 kHz. The template matching system (SPS-8701, Signal Processing Systems) used for isolating action potentials sometimes yielded two well-isolated neurons from a single electrode. When these neurons had well-matched receptive field properties, we were able to collect data from both neurons simultaneously. Horizontal and vertical eye-position signals were measured by a search coil system, sampled at 1 kHz. Unit discharges, eye position traces, and behavioral indicators were saved on disk for off-line analysis.
In each electrode penetration, we searched for neurons that were visually responsive. Once neuronal activity was observed, we mapped the receptive field of the cell by presenting a light bar sweeping over the receptive field. We used bars matched to the size of the receptive field and standardly tested eight directions of stimulus motion, where the direction of motion was orthogonal to the orientation of the bar. During receptive field mapping, the animal simply maintained central fixation and was rewarded every 3 s.
Behavioral tasks
Monkeys were trained on the two tasks illustrated in Fig. 2. All tasks were run in blocks of 10-16 trials. The visual stimulus for a given neuron was either a spot or a bar of optimum length and orientation, depending on which was most effective.
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VISUAL FIXATION TASK. The monkey gazed at a central fixation point (FP; 0.5° diameter). After 500-1000 ms, a visual stimulus (S) was presented briefly (50 ms) in the receptive field on the tangent screen. The monkey was rewarded for holding eye position within a 1.5° window for another 1,000 ms.
MEMORY-GUIDED SACCADE TASK (HIKOSAKA AND WURTZ
1983).
While the monkey fixated on the central fixation point for 500-1,000
ms, a stimulus appeared in the receptive field for 50 ms. The monkey
had to continue to look at the fixation point for 500-1,500 ms after
the stimulus had disappeared. The fixation point was then extinguished,
and the monkey had to make a saccade to the location where the target
had appeared. If the saccade was performed correctly, the target
reappeared 300 ms after the end of saccade, and the monkey was rewarded
for holding the new eye position until the end of the trial, 500-1,000
ms later. This task was used to dissociate sensory activity related to
the stimulus from activity related to the movement. It also allowed us
to assess the impact of making the stimulus the target for a saccade,
in contrast to the fixation task, in which the monkey was free to ignore the stimulus. In the saccade task, the stimulus has immediate behavioral relevance in that the animal must encode its location and
ultimately direct a saccade toward that remembered location.
Data analysis
For each neuron in each task, responses were measured off-line for 10-16 correct trials.
RESPONSE LATENCY. To measure the visual response latency, we first obtained histograms of neuronal activity aligned on stimulus onset. We measured baseline firing rate in the 200 ms prior to stimulus onset in the fixation task. To detect when the firing rate began to differ significantly from this baseline rate, we used a detection window of 20 ms and measured activity starting from visual stimulus onset (0-20 ms). The means of these two distributions (baseline activity and detection interval across all trials) were compared by a t-test. If there was no significant difference, the detection window was shifted 2 ms later (2-22 ms, 4-24 ms, etc) until the activity during the detection period was significantly greater than the baseline activity for two bins in succession. We determined the visual latency as the midpoint of the first bin that was significantly greater than baseline activity. The latency of saccade-related activity (relative to saccade onset) was measured in a similar way. The baseline was defined as the period 200 ms before fixation point offset, and the detection period began 200 ms before saccade onset. All histograms aligned by stimulus onset or saccade onset were visually inspected to ensure that the computed latency was reasonable.
TASK-RELATED ACTIVITY.
We computed the average firing rate during several epochs: visual,
prestimulus, memory, presaccadic, and saccadic. The visual response was
measured as the average firing rate during the 100 ms after the visual
response latency for that neuron. Prestimulus activity was measured as
the average firing rate during the 200 ms before the onset of the
visual stimulus. We did not subtract prestimulus activity from other
response values because, as described in the following text,
prestimulus activity can vary as a function of task. Memory-period
activity was measured as the average firing rate during the 200 ms
before fixation point offset. Saccade-related activity was measured in
two separate epochs: a presaccadic period, 100 ms before saccade onset,
and a postsaccadic period, 200 ms after saccade onset. We chose these
specific epochs to facilitate comparison with previous reports on
responses in other cortical areas (Barash et al.
1991a,b
; Colby et al. 1996
). The saccadic epoch
includes activity occurring during the saccade itself (approximately 40 ms) and in the immediate postsaccadic period.
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RESULTS |
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We recorded from 197 V3A neurons in four hemispheres of two monkeys. We collected complete data sets from 163 V3A neurons for the two main tasks, fixation and memory-guided saccade. For an additional 34 neurons, data were collected only for the memory guided saccade task. For the memory-guided saccade task, we measured activity during four main epochs: prestimulus, visual, memory, and saccade period.
Recording sites
We used three standard measures to identify recording site
locations in visual cortical areas: the anatomical location of the
site, the progression of receptive fields along an electrode penetration, and the size of the receptive field. We reconstructed the
location of recording sites by combining structural MR images with
information about penetration coordinates and depth readings as shown
in Fig. 1. We also examined the progression of the receptive field
locations recorded along each penetration. This procedure was
comparable to that used by Gattass et al. (1988) and was
essential for determining the areal location of each neuron.
The MR image in Fig. 1A shows the ointment-filled tubes that define the plane of the electrode penetrations. The drawing in Fig. 1B shows penetration sites on the cortical surface. Filled dots indicate locations where V3A neurons were recorded, and open circles indicate penetration sites where we did not find V3A neurons. A drawing of the MR image in Fig. 1C shows reconstructions of five electrode penetrations. The penetration indicated by an asterisk passed through striate cortex on the opercular surface, then through the underlying white matter, and then entered the posterior bank of the lunate sulcus. At this location, the receptive fields of the neurons recorded at sites 4 and 5 were on the horizontal meridian (Fig. 1D), indicating that these neurons were on the border between areas V2 and V3. Beyond the posterior bank of the lunate sulcus, there was a quiet zone corresponding to the sulcus, and finally, the penetration crossed into the annectent gyrus. Here the receptive fields (sites 9-14) were closer to the vertical meridian, corresponding to area V3A.
To determine whether a given neuron was in area V3 or V3A, it was
particularly useful to map out changes in locations of receptive fields
along the cortex. In the set of penetrations illustrated, the receptive
field locations recorded along the posterior bank first approached the
horizontal meridian (sites 1-5), then moved toward the vertical
meridian (site 6). At this point the progression of the receptive field
locations reversed its direction (site 7), moving back toward and
across the horizontal meridian. This reversal point indicates the
border between areas V3 and V3A. In this section, the transition to
area V3A was confirmed by the identification of neurons with receptive
fields in the upper visual hemifield (sites 7 and 8). In this region of
cortex, only area V3A has contiguous superior and inferior visual field
representations (Gattass et al. 1988; Van Essen
and Zeki 1978
). Our mapping of the location, extent, and
retinotopic organization of area V3A corresponds well with that
described by Gattass et al. in which the upper field representation of
V3A is adjacent to area V3, and the lower field representation is
adjacent to V4.
A final useful measure for confirming recording site location was the
size of the receptive fields (Fig. 3). We
observed that, at the same eccentricity, receptive fields of neurons in
area V3A were larger than those of V3. This is consistent with the results of Galletti and Battaglini (1989).
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Visual responses and attentional modulation
Neurons gave brisk visual responses to the onset of a small bar or
spot in the receptive field. The mean visual latency was 61.5 ± 25.9 (SD) ms in the fixation task and 61.9 ± 30.4 ms in the
memory-guided saccade task. These latencies are slightly shorter than
those reported for area V3 (mean, 72 ms) in the anesthetized, paralyzed
animal (Schmolesky et al. 1998).
In the fixation task, the visual stimulus in the receptive field was not directly used for the animal's behavior: the task required only that the monkey keep its eyes on the fixation point. We found that the amplitude of the visual response was modulated during a memory-guided saccade task in which the stimulus was made behaviorally relevant. For the neuron illustrated in Fig. 4A, the visual response to the identical stimulus was stronger in the memory-guided saccade task (right) than in the fixation task (left). We also observed the opposite effect: several cells showed a significant decrease in the amplitude of the visual response in the memory-guided saccade task. The neuron shown in Fig. 4B had a strong visual response in the fixation task (left). The response to the identical visual stimulus decreased when the visual stimulus became the target for a saccade (right). Note that in both tasks, the monkey maintained fixation equally well during the visual response epoch.
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At the population level, a subset of V3A neurons was significantly
enhanced or suppressed when the stimulus was made behaviorally relevant. A t-test analysis of response strength in the two
conditions showed that 18% (29/163) of V3A neurons had a significant
increase in response in the saccade task, while 8% (13/163) showed a
significant decrease in visual response (t-test,
P < 0.05). The graph in Fig. 5A plots the mean discharge
rate during the first 100 ms of the visual response in the
memory-guided saccade task against that in the fixation task. Each
point represents the responses of a single neuron in the two tasks. The
has a slope of 1. The degree of modulation of visual responses was
computed as a modulation index, ([visual activity for memory-guided
saccade task] - [visual activity for fixation task])/([visual
activity for memory-guided saccade task] + [visual activity for
fixation task]). The distribution of the index is shown in Fig.
5B. A modulation index of 0 indicates that there was no
difference in the visual response between the two tasks. The graph
shows that visual responses in subsets of neurons were significantly
enhanced or suppressed when the stimulus became the target for a
saccade. The number of neurons that showed a significant increase was
greater than the number of neurons that showed a significant decrease
(
2 test, P = 0.014).
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Modulation of prestimulus activity by expectation of a visual stimulus
In both the fixation task and the memory-guided saccade task, a period of 500-1,000 ms intervened between attainment of fixation and the onset of the visual stimulus. We found that activity even in this prestimulus epoch was modulated by the task and was typically greater in the memory-guided saccade task. We compared this prestimulus activity in the two tasks for each neuron. These tasks were done in blocks of trials, thus the monkey could anticipate in the memory-guided saccade task that a behaviorally relevant stimulus was about to appear. The neuron in Fig. 6 shows an increase in activity before the stimulus appeared in the memory-guided saccade task compared with the fixation task. Note that, for this neuron, the visual response itself was not modulated significantly by the task relevance of the visual stimulus. The animal maintained fixation equally well during both tasks.
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This increase in prestimulus activity was common in the memory guided
saccade task. Thirty-seven of 163 neurons (23%) showed significant
task-related modulation in prestimulus activity (t-test, P < 0.05). Among these, 33 neurons exhibited greater
activity in the memory-guided saccade task (Fig.
7A). To quantify the magnitude of the change in prestimulus activity across the entire population of
cells, a modulation index was computed ([prestimulus activity for
memory-guided saccade task] - [prestimulus activity for fixation task])/([prestimulus activity for memory-guided saccade task] + [prestimulus activity for fixation task]). Prestimulus activity was
quantified as the mean firing rate in the 200 ms preceding stimulus
onset for both tasks. The distribution of the index for the population
(Fig. 7B) illustrates that the tendency of the population
was toward increased activity in the prestimulus epoch in the
memory-guided saccade task (2 test,
P < 0.0001).
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Relationship between modulation of visual responses and prestimulus activity
As described in the preceding sections, we observed modulation of V3A neuron activity in two distinct epochs, prestimulus and visual activity, in the memory-guided saccade task as compared with the fixation task. To examine whether neuronal activity in these two epochs could be modulated independently, we classified V3A neurons into two groups: neurons that showed an enhancement (Fig. 8A) or a suppression (Fig. 8B) of the visual response in the memory-guided saccade task as compared with the fixation task. For each group, we plotted the mean firing rate in the prestimulus epoch of the memory-guided saccade task against that of the fixation task. The majority of neurons in both groups showed an increase in prestimulus activity for the memory-guided saccade task. The independent modulation of visual and prestimulus activity shown in Fig. 8B suggests that separate mechanisms may be involved in their modulation.
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Memory-period activity
The majority of V3A neurons showed a suppression of activity
during the memory period relative to the prestimulus period. The most
common pattern of response in the memory-guided saccade task was for a
neuron to show an increase in activity before stimulus onset and then a
brisk visual response, followed by suppression during the memory
period. For the neuron illustrated in Fig.
9, activity during the memory period
dropped below that in the prestimulus period. This suppression often
lasted until fixation point offset or even until saccade onset, as in
the neuron shown. We carried out three different comparisons to analyze
the degree of suppression during the memory period. First, we compared
the firing rate during the memory-period activity to the prestimulus
activity for each cell (Fig.
10A). Fifty-nine of 197 (30%) V3A cells showed a significant difference between prestimulus
activity and memory activity. Among these, 49 (83%) neurons showed a
significant suppression of activity in the memory period as compared
with the prestimulus period (t-test, P < 0.05). This result indicates that more neurons tended to show decreased
activity during the memory period compared with prestimulus activity
(2 test, P < 0.0001).
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Decreased activity during the memory period can be explained in at least two ways. On the one hand, it may be due to active suppression. On the other hand, it may reflect a return to the "true" baseline activity level as measured in the fixation task. As shown in the preceding text, prestimulus activity was increased in the memory-guided saccade task compared with fixation, and memory-period activity thus may appear to be suppressed only relative to this elevated baseline. We therefore carried out a second analysis in which we compared memory-period activity with activity after the visual response in the fixation task (200-ms period before trial end) as shown in Fig. 10B. We chose this time period in the fixation task to match the epoch during which memory-period activity was measured in the saccade task. Seventy-seven of 163 neurons (47%) showed reduced memory-period activity compared with poststimulus activity in the fixation task. Among these, 15 neurons (9%) showed a significant decrease (t-test, P < 0.05) while 24 neurons (15%) showed a significant increase (t-test, P < 0.05). The difference in the number of neurons that showed a significant increase or decrease was not significant (X2 test, P = 0.14). This analysis indicates that for at least 9% of V3A neurons, decreased activity during the memory period reflects an active suppression.
Finally, in the third analysis, we compared activity during the memory period with baseline activity in the fixation task (Fig. 10C). About half of neurons (75 of 163, 46%) showed memory-period activity that went below the baseline level in the fixation task. This reduction was significant for a subset of neurons (15 of 163, 9%) while 21 neurons (13%) showed a significant increase during the memory period when compared with the fixation task baseline. Again, this analysis indicates that for at least a subset of V3A neurons decreased memory-period activity is produced by an active suppression. Taken together, these three analyses indicate that both mechanisms, active suppression and a return to the original baseline, contribute to the decrease in memory-period activity.
Saccade-related activity
The majority of V3A neurons, 148 of 197 (75%), were active around the time of the saccade. Note that we call this "saccade-related activity," although the activity during this epoch does not reflect only saccade signals. Rather activity in this epoch probably reflects a contribution of reafferent visual signals, orbital position signals, and saccade signals. An example of a neuron with both a visual response and activity around the saccade is shown in Fig. 11. On the left, the rasters are aligned on stimulus onset and the histogram shows a visual response to the appearance of the stimulus in the receptive field. On the right, the rasters are aligned on the beginning of the saccade and show that the neuron became active 50 ms after the onset of saccades directed toward the receptive field. The neuron in Fig. 9 also showed postsaccadic activity.
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We measured the latency of saccade-related activity as the time at
which activity became significantly higher than that in the memory
period (see METHODS). Among the neurons that showed activity around the saccade, the majority (133 of 148 neurons, 90%)
were most active after saccade onset (postsaccadic activity): very few
(15 of 148, 10%) started firing before saccade onset (presaccadic
activity). The histogram in Fig.
12A shows the distribution of latencies of saccade-related activity relative to the saccade onset.
The negative latency values represent activity starting before saccade
onset, and positive values represent activity that follows saccade
onset. The mean latency for the postsaccadic activity was 99.4 ± 65.5 (SD) ms after saccade onset (133 cells); the mean latency for the
presaccadic activity was 69.2 ± 34.2 ms (15 cells).
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The onset of postsaccadic activity was usually sharp and easily determined, in contrast to the onset of long preludes (presaccadic activity), which were more gradual and lower in amplitude. The graph in Fig. 12B compares the level of activity before (100-ms duration) and after (200-ms duration) the beginning of the saccade. For most V3A neurons (118 of 148, 80%), activity after saccade onset was stronger than activity before saccade onset. A t-test analysis indicated that 66 of 148 neurons (45%) had significantly stronger postsaccadic activity than presaccadic activity (P < 0.05). Only 2 of 148 neurons showed significantly stronger presaccadic activity. As shown in Fig. 12A, the majority of cells started firing within 150 ms after saccade onset. Note that the saccade target (the visual stimulus) reappeared only 300 ms after the saccade offset, so the activity of these neurons was not a visual response to the target itself. The duration of activity around the saccade was variable. The duration of saccade-related activity for 98 of 148 (66%) neurons was <300 ms. There were also some cells (28/148, 19%) whose saccade-related activity lasted more than 600 ms. This activity usually lasted until the monkey broke fixation from the target. This long-lasting activity might be related to fixation at a certain orbital position, rather than to the saccade itself.
For most V3A neurons, visual activity was stronger than the activity
around the saccade. The graph in Fig.
13 compares the mean spike frequency
during the first 100 ms of the visual response to the mean spike
frequency of the postsaccadic burst for a given neuron in the
memory-guided saccade task. A t-test analysis revealed that
93 of 148 neurons (63%) had statistically stronger visual activity
(P < 0.05). On the other hand, 3 of 148 neurons (2%) showed significantly stronger saccade activity than visual response. The V3A neurons that had significantly larger sensory responses were
far more common than those that had larger saccade responses (2 test, P < 0.0001).
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The saccade-related activity in V3A neurons showed a variety of patterns. Although it is beyond the scope of this report, we observed that saccadic activity varied in relation to several factors, including saccade direction, amplitude, orbital position, and background luminance of the screen. Saccadic activity cannot be solely explained by reafferent visual signals because it was still observed in total darkness. We measured the activity of 20 V3A neurons in total darkness with a visual stimulus presented by a light emitting diode. All of these neurons showed saccadic activity in the routine experimental condition. Among them, 18 neurons also showed activity in relation to saccades made in total darkness. In Fig. 14, the monkey made memory-guided saccades to the same target location in complete darkness (left) or dim light (right). Both neurons showed postsaccadic activity even in total darkness. Eight of 18 neurons showed stronger activity for the dim-light condition than for the complete-dark condition (Fig. 14A); the other 10 showed similar or even greater saccade activity in complete darkness (Fig. 14B). These results suggest that some V3A neurons encode pure saccade-related signals while others encode a mixture of visual and saccade signals during the saccade epoch.
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DISCUSSION |
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We have found that V3A neurons exhibit different levels of activity, before, during, and after presentation of a visual stimulus as a function of the task context in which the stimulus is presented. In particular, in the memory-guided saccade task, as contrasted to the passive fixation task, prestimulus activity is often higher, the visual response is often stronger, and poststimulus (memory) activity is often lower. Further, we have found that many V3A neurons fire after the onset of a saccade, even in the dark. Taken together, these findings indicate that neuronal activity in area V3A is subject to significant nonvisual influences. These may reflect its participation in a variety of processes beyond passive elaboration of retinal signals, including anticipation, attention, and the representation of locations relative to nonretinal reference frames.
Area V3A is located adjacent to and has strong connections with
parietal area LIP. Neurons in area LIP also exhibit visual, prestimulus, memory, and saccade-related activity (Andersen et al. 1990b; Barash et al. 1991a
,b
; Colby
et al. 1996
; Goldberg et al. 1990
). Using the
same memory-guided saccade task, we are now able to compare directly
neuronal responses in areas V3A and LIP. In the following sections, we
discuss the activity found in area V3A in relation to that in area LIP
and other cortical areas. We then discuss the potential sources and
functional significance of extraretinal inputs to area V3A.
Behavioral relevance of the stimulus modulates visual responses in V3A
Sensory responses of V3A neurons were modulated when the
stimulus was made relevant for the animal's behavior. In both the fixation task and the memory-guided saccade task, the monkey fixated on
the fixation point, and the same visual stimulus was presented in the
identical location in the receptive field. For both tasks, the abrupt
onset of the visual stimulus must have attracted the monkey's
attention to some degree (Yantis and Jonides 1984). The modulation of this visual response in the memory-guided saccade task is
presumably due to additional top-down attentional processes related to
the requirement that the information provided by the stimulus be used
to guide the animal's subsequent behavior.
Modulation of visual responses to stimuli that are the targets for eye
movements, or are behaviorally relevant in other ways, has been
observed in several cortical areas, including extrastriate cortex
(Fischer and Boch 1981; Maunsell 1995
;
Moran and Desimone 1985
; Motter 1993
),
parietal cortex (Bushnell et al. 1981
; Robinson et al. 1978
), and the frontal eye field (Goldberg and
Bushnell 1981
; Wurtz and Mohler 1976
). In area
LIP, in particular, the amplitude of the visual response reflects
whether or not attention is allocated to the stimulus (Colby et
al. 1996
; Goldberg et al. 1990
; Gottlieb
et al. 1998
; Kusunoki and Goldberg 1995
).
Two-thirds of LIP neurons show significant enhancement of the visual
response when the stimulus is made behaviorally relevant (Colby
et al. 1996
). Moreover, there is a strong correlation between
the degree of enhancement in the memory-guided saccade task, in which a
saccade is required, and in the peripheral attention task, which
involves a manual response. These observations suggest that modulation of visual responses in the memory-guided saccade task reflects top-down
attentional processes. While the proportion of neurons in area V3A that
exhibit enhancement is smaller than that in area LIP or the FEF, it may
also reflect a top-down signal, as it does in these higher-order areas.
In the present study, we observed not only significant increases but
also significant decreases in the visual response of V3A neurons when
the stimulus was made behaviorally relevant. Suppression of visual
responsiveness to attended stimuli has been reported previously in
parietal cortex. Robinson et al. (1995) observed neurons
whose visual response was suppressed if the monkey was directed to
shift its attention to the spatial location of that stimulus by a cue
that appeared just before the stimulus. This effect lasted only for a
period of less than 400 ms. In our experiment, however, the interval
between visual stimulus presentations (inter-trial interval) was
several seconds. Thus the attentional suppression observed by Robinson
et al. probably reflects a different mechanism from that operating on
area V3A. The mechanism in V3A may be more similar to that observed in
area 7A by Steinmetz et al. (1994)
. They showed that
area 7A neurons exhibited reduced visual responsiveness in a delayed
match to sample task. When the location of the stimulus matched the
remembered cue location, the visual response to the target was
significantly attenuated. This effect lasted as long as the monkey paid
attention to the cued location. In our experiment, the visual stimulus
was presented repeatedly at the same location, and the attenuation of
visual response we observed may be explained by the same mechanism.
Reduced responsiveness to attended stimuli has also been reported for
neurons in extrastriate cortex. Motter (1993) reported that enhancement of visual responses was observed for 70% of both V1
and V2 neurons when focal attention was directed toward the receptive
field location. In contrast, approximately half of neurons in area V4
showed a greater, and half showed a reduced visual response. Recent
results from Ghose and Maunsell (1999)
suggest that the
degree of attentional modulation observed in area V4 depends critically
on the specifics of the task and the training history of the animal.
Task context modulates prestimulus activity
We found that the rate of background activity during fixation was modulated by the animal's anticipation of the onset of a behaviorally relevant stimulus. In the memory-guided saccade task, the monkey could anticipate that a visual stimulus would appear in the receptive field and that this stimulus will require a particular response (a saccade). In this task, there was an increase in activity before the onset of the stimulus. On the other hand, in the fixation task, the monkey could equally well anticipate that a stimulus was about to appear in the receptive field because a single stimulus location was used for each neuron. Baseline activity, however, was generally less in the fixation task than in the memory-guided saccade task, presumably because the stimulus in the fixation task was not going to be directly used for the monkey's behavior. The buildup of activity preceding stimulus onset may reflect the voluntary allocation of attention to the location where the monkey expects a behaviorally relevant stimulus to appear.
The increase of baseline activity prior to the onset of a behaviorally
relevant stimulus inside the receptive field has also been documented
in area LIP, where 45% of the neurons showed significant increases in
activity (Colby et al. 1996). Similar observations have
been made in area V2 and in ventral stream area V4 (Luck et al.
1997
). In these areas, the baseline firing rate was 30-40% higher when the animal was cued to attend to a particular stimulus location within the receptive field, even when no stimulus was presented there. This finding is congruent with observations from human
functional imaging studies. Directing attention to a peripheral target
location, and anticipation of the onset of visual stimuli at that
location, led to an increase in baseline activity in visual areas V1,
V2, and V4, as well as in dorsal stream areas MT and V3A
(Kastner et al. 1999
).
One could argue that modulation of prestimulus activity and visual responsiveness is due to nonspecific effects, such as a change in arousal or changes in overall responsivity in the recorded neuron. Our results indicate, however, that neurons that showed an increase in baseline activity did not necessarily show an enhancement of the visual response. Likewise, neurons that showed a suppression of the visual response were just as likely to show increased baseline activity as those that showed enhancement of the visual response. The fact that modulation in prestimulus activity and modulation of visually evoked activity are not tightly coupled suggests that these two effects are generated independently. This, in turn, argues against their common mediation by nonspecific influences.
Suppression of memory-period activity
Many neurons in area V3A showed reduced activity during the memory period. This suppression could simply reflect enhanced prestimulus activity compared with that in the fixation task. As activity returned to the original fixation baseline level during the memory period, it may appear to be suppressed relative to the elevated prestimulus activity. In fact, many neurons did show the same level of activity in the memory period and in the pre- or poststimulus period in the fixation task. However, we also found that some neurons showed less memory activity than pre- or poststimulus activity for the fixation task, indicating that active suppression does take place during the memory period.
Sustained activity during the memory period, under conditions in which
the monkey is remembering a location coincident with the neuron's
receptive field, has been reported in many other brain areas. In the
memory-guided saccade task, neurons in prefrontal regions increase
their activity while monkeys remember particular spatial locations
(Chafee and Goldman-Rakic 1998; Funahashi et al.
1989
, 1993
; Kojima and Goldman-Rakic 1982
, 1984
;
Rao et al. 1997
) or visual patterns (Miller et
al. 1996
; O Scalaidhe et al. 1997
; Rao et
al. 1997
; Wilson et al. 1993
). In these tasks,
the elevation of memory-period activity was location specific:
sustained activity was observed when the remembered location was within the receptive field of the neuron. Memory-period activity was suppressed when the animal was required to make a saccade in a direction opposite to the location of the receptive field
(Funahashi et al. 1993
). Memory-period activity has also
been observed in the frontal eye field and supplementary eye field
(Chen and Wise 1995a
,b
), premotor cortex (Wise
and Mauritz 1985
), and caudate nucleus (Hikosaka et al.
1989
).
In parietal cortex, sustained activity during the memory period has
been observed in both area 7A (Constantinidis and Steinmetz 1996) and LIP (Barash et al. 1991a
,b
;
Chafee and Goldman-Rakic 1998
; Colby et al.
1996
; Gnadt and Andersen 1988
). Suppression of
activity during the period when the monkey is remembering the location
of a target presented in the neuron's receptive field has been
reported only rarely. In area LIP, about 10% of the population of
neurons showed suppression during the memory period (Barash et
al. 1991a
) (Fig. 3, B and D). Another
place where suppression has been observed is the substantia nigra
(Hikosaka and Wurtz 1983
). Substantia nigra neurons,
unlike those in LIP and V3A, have a high sustained level of baseline
activity, and both sensory and memory signals are reflected in
decreases in activity. Further investigations of extrastriate cortex
should reveal whether suppression of activity during the memory period
is common or unique to area V3A.
Saccade-related activity
We found that most V3A neurons became active shortly after the
onset of a saccade toward the receptive field. This activity cannot be
explained solely by visual stimulation during saccades because saccadic
activity occurred even in complete darkness. It is unlikely that area
V3A contributes to saccade generation, given that most neurons showed
postsaccadic instead of presaccadic activity. The predominantly
postsaccadic activity we observed in V3A contrasts with the
predominantly presaccadic signals seen in area LIP (Barash et
al. 1991a). Rather, saccadic activity in area V3A was similar
to the postsaccadic activity observed in area 7A (Barash et al.
1991a
).
Postsaccadic activity has been observed in many brain areas. The
functional significance and neuronal mechanisms, however, may differ
depending on the area. Postsaccadic activity has been observed in the
thalamic internal medullary lamina (Schlag and Schlag-Rey
1983), pulvinar (Robinson et al. 1986
),
posterior cingulate cortex (Olson et al. 1996
), area V6A
(Nakamura et al. 1999
), hippocampal, and inferotemporal
areas (Ringo et al. 1994
). Visual areas such as V4, V3,
V2, and V1 also exhibit postsaccadic activity when tested in dim light
(Leopold and Logothetis 1998
). Nakamura et al.
(1999)
found that V6A neurons responded best immediately after a saccade into the "eye-position field." They concluded that
areaV6A neurons encode the initial arrival of the eye into the eye
position field rather than the continued presence or the movement of
the eye within the eye-position field. We also observed that some V3A
neuron showed long-lasting postsaccadic activity; this indicates that
postsaccadic activity may reflect eye position signals. Postsaccadic activity is also common in dorsolateral prefrontal cortex, where it
depends both on the direction of the saccade and the behavioral context
in which it is performed (Funahashi et al. 1991
).
Funahashi et al. suggested that postsaccadic activity in prefrontal
cortex may play a critical role in actively terminating delay-period activity. More generally, saccade-related activity in visual areas such
as V3A may reflect a corollary discharge signal. Recent work in our
laboratory indicates that visual signals in V3A are spatially updated
in conjunction with saccades (Nakamura and Colby 1999
), presumably as a result of corollary discharges from eye movement commands. In sum, the postsaccadic activity observed in the present experiment is probably a mixture of signals including saccade-related, eye position, visual reafference due to saccades, and corollary discharge signals.
Sources and functions of extraretinal inputs to area V3A
Previous studies have shown that visual responses in area V3A are
subject to modulation by extraretinal inputs. Galletti and Battaglini (1989) showed that the visual responsiveness in
about half of the population was influenced by the animals' direction of gaze. We have likewise observed eye-position-dependent modulation of
visual activity (Nakamura and Colby 1998
), which will be
the subject of a separate report. Galletti and colleagues also showed that most V3A neurons can distinguish between actual movements of the
stimulus in the receptive field and equivalent movements of the retinal
image induced by eye movements (Galletti et al. 1990
).
These findings suggest that area V3A takes both visual information and
extraretinal signals into account for accurate spatial analysis.
Further, our findings suggest that there are additional extraretinal
signals in area V3A that may be useful for analysis of the visual environment.
Area V3A has access to information from many sources. Sources of visual
input include areas V2 (Gattass et al. 1997), V3
(Felleman et al. 1997
), and V4 (Felleman and Van
Essen 1983
). There is also a direct but very sparse projection
from V1 (Van Essen et al. 1986
; Zeki 1978a
,
1980
). Girard et al. (1991)
showed that while V1
was deactivated, 30% of neurons in area V3A were still responsive to
visual stimulation, while almost all neurons in areas V2 and V3 lost
their visual responsiveness. This finding indicates that the proportion
of driving input to area V3A from primary visual cortex is less than
that from the areas V2 and V3. Dorsal stream extrastriate inputs to V3A
also arise from the middle temporal area, which is involved in motion
analysis (Ungerleider and Desimone 1986
), the medial
superior temporal area, which is related to generation of smooth
pursuit eye movement (Boussaoud et al. 1990
), the fundus
of the superior temporal visual area (Boussaoud et al.
1990
), and the parieto-occipital area (Colby et al.
1988
).
Potential sources of attentional and saccade signals include frontal
and parietal areas. Area V3A has reciprocal connections with parietal
areas (Andersen et al. 1990a; Baizer et al.
1991
; Blatt et al. 1990
; Cavada and
Goldman-Rakic 1989
; Felleman and Van Essen 1991
;
Morel and Bullier 1990
), including the LIP, which is
important for shifting attention and spatial analysis. Another potential source of attentional and saccade-related signals is the
frontal eye field (Schall et al. 1995
; Stanton et
al. 1995
). In addition to cortical areas, certain ascending
projections may relay extraretinal signals to area V3A. In particular,
there is a projection from superior colliculus via the pulvinar
(Benevento and Rezak 1976
; Girard et al.
1991
; Harting et al. 1980
).
In sum, area V3A is an important link between early visual areas and the sensorimotor integration areas of the parietal and frontal cortex. The heretofore unsuspected anticipatory and attentional signals present in V3A suggest that it could participate in these cognitive functions. While the proportion of neurons modulated and strength of the modulation are less than that observed in areas LIP or FEF, it is striking that even at this stage neurons area susceptible to top-down influences. A question for the future is the extent to which feedback about eye movements may influence the spatial representation in area V3A. The convergence of retinal and extraretinal signals in area V3A suggests that V3A is suited to play a role in both visual and cognitive functions.
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ACKNOWLEDGMENTS |
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We thank Dr. Donald S. Williams for performing the MR scan, K. Rearick for animal care, and J. Nadler for helping with data analysis. We are also grateful to Drs. Carl Olson, Chris Baker, David Moorman, and Jeffrey D. Schall for comments on the manuscript.
This work was supported by the Uehara Foundation, the Human Frontier Science Program, the EJLB Foundation, the Whitehall Foundation, and National Eye Institute Grants EY-12032 and EY-08098.
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FOOTNOTES |
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Address for reprint requests: C. L. Colby, Dept. of Neuroscience, Center for the Neural Basis of Cognition, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, PA 15260 (E-mail: colby{at}bns.pitt.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 15 November 1999; accepted in final form 4 April 2000.
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