functional role of the ventrolateral prefrontal cortex in decision making
TRANSCRIPT
Functional role of the ventrolateral prefrontal cortex indecision makingMasamichi Sakagami and Xiaochuan Pan
To make deliberate decisions, we have to utilize detailed
information about the environment and our internal states. The
ventral visual pathway provides detailed information on object
identity, including color and shape, to the ventrolateral
prefrontal cortex (VLPFC). The VLPFC also receives
motivational and emotional information from the orbitofrontal
cortex and subcortical areas, and computes the behavioral
significance of external events; this information can be used for
elaborate decision making or design of goal-directed behavior.
In this review, we discuss recent advances that are revealing
the neural mechanisms that underlie the coding of behavioral
significance in the VLPFC, and the functional roles of these
mechanisms in decision making and action programming in
the brain.
Addresses
Brain Science Research Center, Tamagawa University Research
Institute, Tamagawa-gakuen, 6-1-1 Machida, Tokyo 194-8610 Japan
Corresponding author: Sakagami, Masamichi
Current Opinion in Neurobiology 2007, 17:228–233
This review comes from a themed issue on
Cognitive neuroscience
Edited by Keiji Tanaka and Takeo Watanabe
Available online 9th March 2007
0959-4388/$ – see front matter
# 2007 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.conb.2007.02.008
IntroductionDecision making enables humans to select appropriate
actions in given circumstances. Some decisions can be
made with little effort; others require careful consider-
ation of options. When we select an appropriate action
based on visual information, at least two neural pathways
provide cues for decision making: the ventral pathway,
from the primary visual cortex (V1) to the inferotemporal
cortex, mediates object recognition and contributes to the
formation of our cognitive world; the dorsal pathway, from
V1 to the parietal cortex, determines the spatial layout of
objects and computes the disposition of objects for actions
[1–3]. Anatomical data further reveal that the inferotem-
poral cortex has many efferents to the prefrontal cortex,
especially to the ventrolateral prefrontal cortex (VLPFC)
[4,5]. By contrast, the parietal cortex projects primarily to
premotor cortex and dorsolateral prefrontal cortex
(DLPFC) [6,7]. These projections to the prefrontal
Current Opinion in Neurobiology 2007, 17:228–233
cortex, which are crucial for decision making, are referred
to as the extended ventral and extended dorsal pathways.
Whereas the extended dorsal pathway can quickly trans-
form sensory information into motor commands in a
reactive and automated fashion, the extended ventral
pathway, which carries detailed information about the
circumstances surrounding a decision, provides flexibility
in decision making [8,9��]. In this article, we review
experimental data from the past two years that are reveal-
ing the mechanisms that underlie decision making in the
extended ventral pathway, and in particular the func-
tional roles of the VLPFC.
Ventrolateral prefrontal cortex andbehavioral significanceThe lateral prefrontal cortex (LPFC) is thought to con-
tribute to numerous cognitive functions as an interface
between sensory areas and motor areas [10–13]. The most
popular view credits the LPFC with mediating working
memory functions [14–16]. More specifically, the tight
connections between the ventral pathway and VLPFC
and between the dorsal pathway and DLPFC, combined
with the respective ‘what’ and ‘where’ interpretation of
these ventral and dorsal pathways, prompted Goldman-
Rakic to suggest that the VLPFC mediates object-based
working memory whereas the DLPFC has an analogous
spatial function [16]. Although early investigations with
both nonhuman primate and human participants sup-
ported this distinction [17,18], more recent evidence from
imaging studies and lesion experiments begs to differ
[19–23].
The inferotemporal cortex, which is part of the ventral
pathway, does not project directly to the premotor and
primary motor (M1) cortical areas, but sends information
to the LPFC, especially the VLPFC [4,5]. In turn, the
VLPFC has rich connections with the premotor cortex
[5,24]. Thus, in the extended ventral pathway, the
VLPFC could translate information from the ventral
pathway, such as color and shape, into precursors for
motor commands in the premotor cortex. Single-unit
studies have suggested that neurons in the primate LPFC
encode representations of actions to be made in response
to stimuli to obtain reward, given that the activity of these
neurons predicts impending action in monkeys [25–29].
The representation is characterized best as the behavioral
significance of the cue stimulus [25–27]. For example,
Sakagami and Niki [27] trained monkeys to make a go or
no-go response depending on the physical feature of a cue
stimulus. Many neurons in the LPFC showed differential
visual responses to the cue stimulus, depending not on
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Functional role of the ventrolateral prefrontal cortex in decision making Sakagami and Pan 229
physical features but on whether the relevant feature of
the cue stimulus indicated a go or no-go response. The
neuronal activity was not simply related to motor execu-
tion because there was a delay period between the cue
presentation and the go or no-go response.
Sakagami and colleagues [28–30] trained monkeys in a go/
no-go selective-attention task to discriminate colored
random-dot patterns on the basis of color (color condition)
or motion (motion condition). In the VLPFC, the
majority of neurons showed go/no-go differential activity
only in the color condition (C neurons). In the DLPFC
and areas around the arcuate sulcus, most neurons dis-
criminated between go and no-go in both color and
motion conditions (CM neurons), whereas a minority of
neurons transmitted the information only in the motion
condition (M neurons). When a shape-discrimination
condition was added, the majority of C and CM neurons,
but not M neurons, showed differential go/no-go activity.
Thus, visual information from the ventral pathway
seemed to be classified in terms of behavioral significance
in the VLPFC, and this information would be sent to the
DLPFC and the arcuate area to be integrated with
information from the dorsal pathway into a precursor of
the motor command. This hierarchical functional struc-
ture is consistent with anatomical data [24,31]. These
results suggest that the VLPFC computes behavioral
significance by integrating information about the target
with situational factors. Indeed, VLPFC neurons have
also been reported to reflect abstract codes relating to
context [27,32] and category [33,34��].
Integration of cognitive and motivationalinformationOur decision making depends on motivational state as
well as cognition. The LPFC, particularly the VLPFC,
also receives projections from the orbitofrontal cortex and
subcortical areas such as the midbrain and amygdala
[35,36], which are involved in processing motivational
and emotional information [37–39]. Thus, the VLPFC
might integrate cognitive and motivational information to
guide flexible goal-directed behavior (see also review by
Watanabe, in this issue). Many studies show reward-
modulation effects in the cognitive activity of LPFC
neurons [40–43,44��,45�]. For example, Kobayashi et al.[42] used a memory-guided saccade task with an asym-
metric reward schedule to investigate reward modulation
of spatial working-memory neurons in monkey LPFC. In
this experiment, the color of the target cue indicated
whether a correct response would be followed by reward.
Reward-modulated neurons tended to be located more
ventrally in the LPFC relative to pure spatial-coding
neurons. When the spatial position indicated the presence
or absence of reward, the difference disappeared [45�].Kobayashi et al. [42] also suggested that the integration is
not a simple summation, but a non-linear increase of the
amount of transmitted information with respect to target
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position. In other words, reward information is used to
strengthen the cognitive function (spatial discrimination),
which leads to performance enhancement.
Many LPFC neurons showed predictive activity in the
absence of reward (or in the presence of a small reward)
[41,42,46]. This predictive code for the absence of reward
could be integrated with cognitive information in LPFC
neurons [42,46]. These data lead to the question of how
LPFC neurons process aversive information. Kobayashi
et al. [44��] compared the effects of reward and punish-
ment on the cognitive neural code in the LPFC. They
trained a monkey on a memory-guided saccade task in
three conditions: reward, punishment and sound only (i.e.
no punishment or reward). Performance was best in the
reward condition, intermediate in the punishment con-
dition and worst in the sound-only condition. The
majority of task-related neurons showed cue and/or delay
activity that was modulated only by reward. Other
neurons were modulated only by punishment, although
these were fewer than the reward-modulated neurons.
Some neurons were modulated by both positive and
negative reinforcers (that is, they reflected general
reinforcement or attentional processes), but these were
also fewer than reward-modulated neurons. These results
indicate that information on reward and punishment is
processed differentially in the LPFC, and that this integ-
ration is not yet completed at the LPFC stage of infor-
mation processing.
Kobayashi et al. [45�] compared the reward-modulated
neuronal activity in the LPFC, including the VLPFC,
with that in the caudate nucleus in an asymmetrically
rewarded memory-guided saccade task. They found that
neurons encoding purely spatial information were more
common in the LPFC, whereas neurons that had reward-
anticipating pre-cue activity were more prevalent in the
caudate nucleus. Neurons reflecting both spatial and
reward information were found in both areas. The activity
of these neurons in both areas was highest in trials in
which the target cue was presented in the receptive field
and the position was associated with reward. However, a
substantial difference was observed in trials in which
the target cue was presented in the receptive field but
the position was associated with non-reward. It should be
noted that the monkeys performed the task well even in
non-rewarded trials because a correction method was
used, so that the monkeys still had to make a correct
response to proceed to the next trial. LPFC neurons
showed activity patterns that corresponded well with
the actual behavior, suggesting that LPFC integration
neurons use a long-term scale of reward history for their
learning process. By contrast, neurons in the caudate
nucleus hardly responded at all to a cue in the receptive
field in non-rewarded trials, suggesting that the scale of
reward history for integration in the caudate neurons is
much smaller. Recently, several studies found a similar
Current Opinion in Neurobiology 2007, 17:228–233
230 Cognitive neuroscience
contrast between LPFC and caudate neurons [47,48].
Data that are consistent with this interpretation were also
reported in functional magnetic resonance imaging
(fMRI) studies [49,50].
Several circuits enable the brain to make appropriate
behavioral decisions. Some are based on a relatively
simple input–output relationship, whereas others depend
on the integration of various pieces of complex infor-
mation. The pathways used to integrate different kinds of
information are also distinct, and these decision making
circuits seem to work relatively independently [51].
Among the circuits, one that includes the LPFC can
generate particularly elaborate decisions. Barraclough
et al. [52] recorded from monkey LPFC neurons while
the monkey had to make an appropriate decision con-
sidering the changeable strategy of an enemy (a compu-
ter); they found that LPFC neurons could provide
information that reflected the history of responses and
their outcomes. The characteristics of the LPFC include
the ability to encode abstract and contextual representa-
tions [27,41,53] and the ability to reflect reward history on
a long-term scale [45,49,50]. In particular, the retention of
long-term reward history is the basis for long-term reward
prediction, which is a prerequisite for systematic plan-
ning. Such integration of information could enable elab-
orate decisions to be made with respect to goal-directed
behavior in complex circumstances.
Functional roles of the VLPFC in decisionmakingHow is the output from the VLPFC used in the brain?
The major upstream destination of output from the
VLPFC is the premotor cortex, which in turn sends
projection to M1 [24,31]. The VLPFC also has dense
interconnections with the DLPFC, which also projects to
the premotor cortex. In the DLPFC and premotor cortex,
VLPFC output that relates to behavioral significance
could be integrated with action commands from the
extended dorsal pathway to finalize motor decisions.
The VLPFC also has feedback connections to sensory
association areas. Recently, several fMRI studies have
demonstrated that the prefrontal cortex has control over
sensory processing [54–56,57��]. Because feedback infor-
mation must include behavioral significance, sensory
areas can utilize this information to improve their descrip-
tions of circumstances that are relevant to goal-directed
behavior. Representation of an object in the inferotem-
poral cortex is influenced by its acquired behavioral
significance [58], and the feedback signal from the LPFC
could be used for retrieval from long-term memory stored
in the inferotemporal cortex [59]. Feedback from the
VLPFC about sensory processing can be also routed
via the DLPFC; in this case, information processing in
the dorsal pathway can be modulated by behavioral
significance generated in the VLPFC. Similar modulation
Current Opinion in Neurobiology 2007, 17:228–233
can be brought about through the ventral–dorsal inter-
connections within posterior cortices [60]; these connec-
tions carry information about changes in the ventral
pathway, which is controlled by the feedback from the
VLPFC.
Lesion studies in non-human primates and human
patients established that VLPFC dysfunction leads to
lack of inhibitory control of behavior [61–63]. Several
human fMRI studies documented inhibition-related acti-
vation in the VLPFC [64,65]. Single-unit recording
experiments also supported this notion [66,67,68�]. Saka-
gami et al. [66] analyzed the activity patterns of C neurons
in the VLPFC using the go/no-go selective-attention task
with color and motion (as mentioned earlier). The
majority of C neurons showed stronger activity to go-
indicating colors than to no-go colors in the color con-
dition. However, when the activity in the color condition
was compared with the non-differential activity in the
motion condition, it became apparent that almost all C
neurons specifically changed their firing rate for no-go
colors in the color condition, coding the ‘no-go’ meaning
rather than ‘go’. The neural recording data suggest that
the output of C neurons in the VLPFC tells what the
monkey should not do rather than what the monkey
should do. Thus, the VLPFC interprets the meaning
of sensory information, and facilitates decision making
about the forthcoming response by signaling which
responses (prepared by the extended dorsal or other
pathways) should be cancelled or blocked. Inhibitory
control by the LPFC is exerted over not only behavioral
decisions but also perception. Tsushima et al. [57��]provided direct evidence that the LPFC sends inhibitory
signals to control the activity in sensory areas. Subjects
were asked to perform a digital item-recognition task with
task-irrelevant random-dot motion in the background.
The data showed that the LPFC usually suppressed
activity in area MT when this area generated task-irre-
levant noise. Yet, interestingly, the LPFC could not
suppress task-irrelevant activity in area MT when the
motion strength was higher than the threshold of that area
but lower than that of the LPFC.
ConclusionThe VLPFC receives detailed sensory information about
circumstances from the ventral pathway, and motivational
and emotional information from the orbitofrontal cortex
and subcortical areas. Through the integration of this
cognitive and motivational information, the VLPFC com-
putes adaptive codes on the basis of behavioral signifi-
cance, which leads to deliberate decision making or goal-
directed behavior. The output from the VLPFC can
cause information in other areas to adapt in response to
given circumstances because the codes can include both
sensory and motor information. We illustrate in Figure 1
possible routes by which the codes of behavioral signifi-
cance can be carried to other areas (black lines). Through
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Functional role of the ventrolateral prefrontal cortex in decision making Sakagami and Pan 231
Figure 1
The two classic pathways of visual processing (green arrows), the
two extended parallel pathways for decision making (red arrows),
and connections between these pathways (black arrows). The
extended dorsal pathway projects from the parietal cortex (PC) to the
premotor cortex (PM) and the dorsolateral prefrontal cortex (DLPFC);
the extended ventral pathway projects from the inferotemporal cortex
(IT) to the ventrolateral prefrontal cortex (VLPFC). The connection
from PM to the primary motor cortex (M1) (orange) is shared by the
two extended pathways. The VLPFC connects with the DLPFC
(route 1) and the premotor cortex (route 2). The DLPFC projects to
the premotor cortex (route 3) and the parietal cortex (route 5). The
VLPFC has feedback connections to the inferotemporal cortex
(route 4). There are also interconnections between the inferotemporal
and parietal cortical areas (route 6). Additional abbreviation: V1,
primary visual cortex.
route 1, these codes are integrated with those in the
DLPFC, which might be carrying more motor-oriented
and spatial-oriented cognitive information derived from
the extended dorsal pathway. Through routes 2 and 3, the
codes can influence action plans or programs in the
premotor cortex. Through route 4, the sensory descrip-
tions of circumstances can be modulated to be more
suitable for goal-directed behavior. Through routes 5
and 6, the information of behavioral significance can
be reflected in the computation of the extended dorsal
pathway.
We would like to raise three points as areas for future
research. First, we know little about the neural mech-
anisms that generate and organize behavioral signifi-
cance in the VLPFC, particularly abstract codes and
substrates for rules. Second, it is also unclear how the
codes in the VLPFC can be used for behavior or action
programs, although dysfunction of the VLPFC leads to
impulsive behaviors without motor paralysis [12]. Third,
we still have poor knowledge about decision making
based on other modalities relative to decision making
based on vision (although there are some exceptions
[69]).
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AcknowledgementWe thank J Lauwereyns for critical comments. Our work is supported by theHuman Frontier Science Program (MS), by Precursory Research forEmbryonic Science and Technology (MS), and by Grant-in-Aid forScientific Research on Priority Areas (MS) and Tamagawa University COE(MS) from the Japanese Ministry of Education, Science, Sports and Culture.
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Current Opinion in Neurobiology 2007, 17:228–233