Search Target Selection in Monkey Prefrontal Cortex
Ryohei P.
Hasegawa,
Madoka
Matsumoto, and
Akichika
Mikami
Department of Behavioral and Brain Sciences, Primate Research
Institute, Kyoto University, Aichi 484-8506, Japan
 |
ABSTRACT |
Hasegawa, Ryohei P.,
Madoka Matsumoto, and
Akichika Mikami.
Search Target Selection in Monkey Prefrontal Cortex.
J. Neurophysiol. 84: 1692-1696, 2000.
To explore
a visual scene, the brain must detect an object of interest and direct
the eyes to it. To investigate the brain's mechanism of saccade target
selection, we trained monkeys to perform a visual search task with a
response delay and recorded neuronal activity in the prefrontal (PF)
cortex. Even though the monkey was not allowed to express its choice
until after a delay, the response field of a class of PF neurons was
able to differentiate between target and distractors from the very
beginning of their response (135 ms). Strong responses were obtained
only when the target was presented at the field. Neurons responded much
less during a nonsearch task in which saccade target was presented alone in this response field. These results suggest that the PF cortex
may be involved in the decision-making process and the focal attention
for saccade target selection.
 |
INTRODUCTION |
Many studies of prefrontal (PF)
cortex have concentrated on studying the response of neurons to single
spots flashed in the dark. Under these circumstances neurons respond to
stimuli flashed in their receptive fields (Boch and Goldberg
1989
; Funahashi et al. 1990
; Mikami et
al. 1982
; Suzuki and Azuma 1983
). The visual response of PF neurons can be modulated according to the behavioral significance of the stimulus (Boussaoud and Wise 1993
;
Hasegawa et al. 1998b
; Kim and Shadlen
1999
; Rainer et al. 1998
; Sakagami and
Niki 1994
; Watanabe 1986
), for example when the
stimulus in the receptive field is the match in a match-to-sample task
(Hasegawa et al. 1998b
; Rainer et al.
1998
; Rao et al. 1997
). However, in real life
primates choose the targets for saccadic eye movements from complex
visual scenes that contain many distracters as well as targets. In
these experiments we analyzed the response of neurons in PF cortex to
stimuli that served either as targets or distracters in a visual search
task. We show that a subset of PF neurons can distinguish between
targets and distractors and therefore are specialized for saccade
target selection. A preliminary report of this study has been presented
elsewhere (Hasegawa et al. 1998a
).
 |
METHODS |
Two male rhesus monkeys (Macaca mulatta) were trained
to perform a delayed visual search (DVS) task (Fig.
1A). In this task the monkeys
had to fixate a central spot for 1 s (fixation period), after
which an array of 6 small (5° diam) circular gratings appeared at
symmetric locations 20° around the fixation point and remained lit
for 0.5 or 1 s (cue period). Five of the gratings had identical spatial frequencies, fine or coarse, and the remaining had a different spatial frequency. After the gratings disappeared, the monkey had to
hold fixation for another 0.8-1.5 s of variable delay period, and then
the fixation spot disappeared and the monkey had to make a saccade to
the spatial location of the unique stimulus (go period, <1 s) to earn
a drop of water. The uniqueness of the target spatial frequency, not
the absolute value of the spatial frequency, was critical. A given
stimulus could serve as target or distractor, depending on the
frequency of the remaining stimuli. The target and distractor features
(target position and spatial frequency) varied randomly across trials.
For some neurons that were active during DVS trials, we also tested an
oculomotor delayed response (ODR) task (Funahashi et al.
1989
), in which the same set of objects and locations of the
target were used as in the DVS task but presented alone. DVS and ODR
tasks were run in separate blocks that contained 100-300 trials. We
checked the consistency of waveform of spike and frequency of baseline
rate after changing tasks and repeated blocks as far as we could hold
the neuron. We used standard electrophysiological techniques to record
single neuronal activity (Hasegawa et al. 1998b
).
Recording sites were histologically localized in the area anterior to
the arcuate sulcus and medial to the principal sulcus (see Fig.
1B). No eye movement was elicited by intracortical
microstimulation (100 µA) in this area, indicating that the recording
area was outside of the frontal eye field. We generated rasters and
average spike density histograms (binwidth, 10 ms) aligned on the cue onset. To detect significant changes in activity related to search, we
compared cue-period activity with activity during fixation period (400 ms preceding cue presentation). Cue-period activity was defined as an
activity in 200 or 300 ms starting 50, 100, 150, or 200 ms after the
cue onset, which was automatically calculated to maximize activity. For
the analysis on the close time course of population histograms, spike
density function sampled at 1 kHz was convolved with a Gaussian filter
(SD = 10 ms). All experiments were performed in accordance with
the "Guidelines for the Care and Use of Laboratory Animals" of the
National Institutes of Health (1985) and the "Guide for Care and Use
of Laboratory Primates" published by Primate Research Institute of
Kyoto University (1986).

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Fig. 1.
A: sequence of trial events of the delayed visual search
task. The search array appears and then disappears while the fixation
spot is lit. The monkey makes the saccade toward the remembered
location soon after the fixation spot disappears. T and D represent the
target and distractors, respectively. The arrow indicates a saccadic
eye movement. B: schematic drawings of recording sites.
The recorded sites (shaded area) were located anterior to the arcuate
sulcus and medial to the principal sulcus. AS, arcuate sulcus; PS,
principal sulcus. C: search-related activity of a single
prefrontal (PF) neuron. Neural response was shown in each trial
condition. Left and right columns,
respectively, represent "bottom left" and "top right" target
location. Top and bottom rows,
respectively represent "fine" and "coarse" target objects. The
top panel in each condition indicates the search array,
which was presented for 0.5 s while the monkey maintained central
fixation. The target object is the odd item among search array, which
is different from distractors in spatial frequency of checkerboard
pattern. The area surrounded by dashed line and also marked by RF in
each stimulus panel represents a response field for the target object.
In the raster displays, vertical tick marks and circles represent times
of spikes and saccades. Neural responses are aligned on the cue onset.
Left and right vertical lines through rasters indicate the onset of the
search cue and its offset (beginning of the delay period).
|
|
 |
RESULTS |
We recorded the activity of 157 single cells from the dorsolateral
PF cortex (Fig. 1B) in two rhesus monkeys. Of them, 53 (32 from monkey 1 and 21 from monkey 2) showed
neuronal activity during the cue period. Figure 1C shows an
example of a neuron that had a response field specific for a search
target. The neuron responded to the onset of the search array when the
monkey had to find the higher spatial target and it appeared at the
bottom left (Fig. 1C, top left). After a transient response
to the onset of the search array, the activity continued during a delay
period. Activity in both the cue and delay period was significantly
greater than the fixation period (Wilcoxon signed-rank test,
P < 0.05). The neuron responded much less when a
distractor appeared at the same place (Fig. 1C, top right).
The identification of a stimulus as the target determined the response,
not its spatial frequency. When the coarse spatial frequency stimulus
was the target, the neuron responded to it (Fig. 1C, bottom
left), although it did not respond to the stimulus when it was the
distractor. It is also clear from Fig. 1C, bottom right,
that these responses did not depend on the existence of the fine object
in this target-specific response field. Of 53 visual neurons, 34 (64%)
showed significant difference in cue-period activity between trials for
target in the response field and distractors in the field (Mann-Whitney U test, P < 0.05). Of these 34, more than
1/2 of the neurons (n = 20, 61%) did not show a
significantly higher cue-period activity to distractors presented in
the response field than that of the fixation period (Wilcoxon
signed-rank test, P > 0.05).
It could be that the increased response to the search target was merely
due to its selection as a saccade target. We compared the activity in
the DVS task to their activity in a simple ODR task (Funahashi
et al. 1989
), which had the same time course and set of stimuli
as the DVS task. Figure 2A
shows an example tested in both tasks. This neuron had selectivity for
target location in both tasks; we estimated the response field to be a
restricted area covering right and top right. However, there was
difference in magnitude of cue-period activity between DVS and ODR
tasks. The response to the search target in the DVS task was
significantly higher than that to the detection target in the ODR
(Mann-Whitney U test, P < 0.05). For 22 neurons tested, we compared the responses to the target in both tasks
(Fig. 2B). Activity in the DVS task was greater for 19 neurons, and the population activity was also statistically higher
(Wilcoxon signed-rank test, P < 0.001).

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Fig. 2.
A: quantitative analysis for a PF neuron selective to
target location during a delayed visual search (DVS) and an oculomotor
delayed response (ODR) task. Location of each histogram corresponds to
the target location in search array. Neural responses are aligned on
the cue onset (vertical dashed line). The cue was presented for 1 s in this recording session. The polar plots in both tasks show the
average activity in cue-period (solid thick line) and control
(fixation) period (dashed thin line) to 6 target locations. The area
marked by RF and surrounded by a dotted line means the estimated
response field for target location. B: comparison of DVS
and ODR activities for 22 neurons tested.
|
|
Monkeys occasionally made errors in the DVS task, making saccades to a
distractor rather than to the target location. In these error trials
the neuron responded to the target as if it had been a distractor (Fig.
3A), failing to respond even
though the unique stimulus was in the response field. For 23 neurons
with enough error trials for this analysis, we compared magnitude of
responses to target between correct and error trials (Fig.
3B). For 20/23 neurons the response to the target was less
in the error trials than that in correct trials, and the population
activity was also significantly less (Wilcoxon signed-rank test,
P < 0.01).

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Fig. 3.
A: comparison of neuronal responses on 3 types of
correct and error trials in the neuron illustrated in Fig.
2A; response to the target inside the response field on
correct trials (left); response to the target outside
the response field on correct trials (middle); and
response to the target inside the response field on error trials
(right). The response is much less when the target
appears in the response field but the saccade is to a distractor.
Abbreviations are the same as those in Figs. 1 and 2. B:
comparison of averaged activities on correct and error trials for 23 neurons tested.
|
|
As shown in Figs. 1C and 2A, PF neurons showed a
differential activity for the location of the search target during the
cue period. Cue-period activity was often followed by delay- and/or go-period activities. To examine when the neurons selected the target
and how the information could be used for the upcoming saccade, we made
population histograms synchronized on cue onset and saccade onset for
target and distractors in the response field (Fig.
4, top). Information about
target location developed very early (starting about 135 ms after cue
onset) and was maintained through the delay period. Presaccadic
activation appeared just before the monkey made a saccadic eye movement
toward the remembered location of the target. The presaccadic burst and
beak were located at around 250 and 115 ms before the saccade onset,
respectively. Figure 4, bottom, shows a comparison of time
course of activity on DVS and ODR trials. As shown in Fig. 2, PF
activities were enhanced in the search task compared to the detection
trials. Search enhancement began about 180 ms after cue onset and
lasted until 100 ms before the time of saccade, although the difference during the early part of the delay period was smaller.

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Fig. 4.
Preferred vs. nonpreferred location: population (average) activity of
24 PF neurons selective for the target location during the DVS task.
Thick and thin lines represent activity for preferred and nonpreferred
target locations, respectively. The difference in activity during every
500-ms epoch after cue onset trough to saccade onset (0-500,
500-1,000, 1,000-1,500, 1,500-2,000 ms from cue onset and 500-0
ms from saccade onset) between preferred and nonpreferred locations was
significantly higher (t-test, P < 0.05) than the 500-ms epoch before cue onset. DVS vs. ODR task:
population activity of 12 PF neurons selective for the target location
tested in both DVS and ODR tasks. Thick and thin lines represent
activity for preferred target locations on DVS and ODR trials,
respectively. The difference in activity during 1st 500-ms epoch after
cue onset (0-500 ms) and presaccadic epoch ( 500-0 ms from saccade
onset) between DVS and ODR task was significantly higher
(t-test, P < 0.05) than that before
cue onset ( 500-0 ms).
|
|
 |
DISCUSSION |
In these experiments we show that neurons in monkey PF cortex
respond to stimuli in a complex array only when those stimuli dictate a
behavioral choice. Neuronal activity related to visual search has been
well examined in the frontal eye field (FEF) adjacent to the
periprincipal sulcal area from which we recorded. The FEF is thought to
be a cortical center of eye movement (Bruce and Goldberg
1985
), and the visual response of FEF neurons to a peripheral stimulus is enhanced during a saccade task compared to a fixation task
(Goldberg and Bushnell 1981
). Furthermore, Burman and
Segraves showed that FEF neurons were active in saccade planning while the animal scanned a natural image (Burman and Segraves
1994
). Schall and his group (Schall et al. 1995
;
Thompson et al. 1996
) studied the responses of FEF
visuomovement neurons in a search task based on color or frequency
difference. Those neurons gave identical transient responses to target
and distractors and distinguished between target and distractor after
the transient response at around 120-150 ms. Periprincipal neurons
started distinguishing between target and distractors at around 135 ms,
that is, at the same time of FEF neurons, yielding much smaller if any
transient responses to distractors. In this regard they resemble the
response of FEF visuomovement neurons that fail to respond to
distractor stimuli when the monkey was overtrained on a simple color
discrimination task (Bichot et al. 1996
), although the
latency of differential activity was earlier (at around 80 ms). The
differential latency found in our study was consistent with previous
studies in which a match-to-sample paradigm was used to test PF neurons
[around 140 ms by Rainer et al. (1998)
and 100-200 ms
bin by Hasegawa et al. (1998b)
]. While
matching-to-sample is mainly guided by a memory representation, a pure
odd-item search in which target object and location are shuffled
randomly trial by trial may involve different mechanisms. We confirmed
that PF neurons did contribute in early processing of visual search
over the paradigm. Furthermore, we also found that a differential
activity for target location was enhanced on search trials compared to
that on detection trials. This search enhancement may depend on the
level of focal attention. Unlike detection trials, subjects may require
a higher level of focal attention to make sure of the target location
and plan the appropriate choice, especially in a delayed condition. The
enhancement, which was most evident 180 ms after the cue and again
250-100 ms before the saccade, may reflect the increase of focal
attention and the contribution of signaling attentional movement, respectively.
Compared to the FEF neurons, periprincipal neurons do not seem
tied to the outer environment. In general, their onset latency to
visual stimulus is longer than that of FEF neurons, and in some cases
they appear to care less about distractors in the response field. Their
presaccadic burst suggests that they plan or signal directional
saccades long before its execution, but the magnitude of activity could
be modulated by the behavioral context. Further studies are necessary
to make clear the functional differences of both areas. The response
field of periprincipal neurons also differs from the response field in
the other cortices. Feature-based target selection may occur in the
inferotemporal (IT) cortex, which is selective to physical property of
a target object (Chelazzi et al. 1998
). Activity in this
area may be a source of weak selectivity for a target object observed
even in our study. It is possible that lateral intraparietal area
(LIP), a part of the parietal cortex, is involved in finding an
odd-item. LIP neurons represent salient objects in the response field
in a complex visual scene even when stimulus is not a saccade target
(Gottlieb et al. 1998
). LIP may give information of the
location of odd objects to the PF cortex. Thus the PF cortex may
interact with these FEF, IT, and LIP areas to search for a saccade
target among distractors.
 |
ACKNOWLEDGMENTS |
We thank M. E. Goldberg, J. Gottlieb, M. A. Basso, and
J. W. Bisley for repeated discussions, T. Miwa for technical
assistance, and I. Glick for editing of English. R. P. Hasegawa is
a Research Fellow of the Japan Society for the Promotion of
Science (JSPS).
This work was supported in part by the JSPS, the Human
Frontier Science Program, the Mitsubishi Foundation, and the Ministry of Education, Science, Sports and Culture, Japan.
Present address of R. P. Hasegawa: Laboratory of Sensorimotor
Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
 |
FOOTNOTES |
Address for reprint requests: A. Mikami, Dept. of Behavioral
and Brain Sciences, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan (E-mail:
mikami{at}pri.kyoto-u.ac.jp).
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 17 April 2000; accepted in final form 16 May 2000.
 |
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