functional role of the ventrolateral prefrontal cortex in decision making

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Functional role of the ventrolateral prefrontal cortex in decision making Masamichi 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 ([email protected]) 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 Introduction Decision 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 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 and behavioral significance The 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 Current Opinion in Neurobiology 2007, 17:228–233 www.sciencedirect.com

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Page 1: Functional role of the ventrolateral prefrontal cortex in decision making

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

([email protected])

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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Page 2: Functional role of the ventrolateral prefrontal cortex in decision making

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

Page 3: Functional role of the ventrolateral prefrontal cortex in decision making

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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Page 4: Functional role of the ventrolateral prefrontal cortex in decision making

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]).

www.sciencedirect.com

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.

References and recommended readingPapers of particular interest, published within the period of review,have been highlighted as:

� of special interest�� of outstanding interest

1. Ungerleider LG, Mishkin M: Two cortical visual systems. InAnalysis of Visual Behavior. Edited by Ingle DJ, Goodale MA,Mansfield RJW. MIT Press; 1982:549-586.

2. Goodale MA, Milner AD: Separate visual pathwaysfor perception and action. Trends Neurosci 1992,15:20-25.

3. Goodale MA, Kroliczak G, Westwood DA: Dual routes to action:contributions of the dorsal and ventral streams to adaptivebehavior. Prog Brain Res 2005, 149:269-283.

4. Ungerleider LG, Gaffan D, Pelak VS: Projections from inferiortemporal cortex to prefrontal cortex via the uncinate fasciclein rhesus monkeys. Exp Brain Res 1989, 76:473-484.

5. Petrides M, Pandya DN: Comparative cytoarchitectonicanalysis of the human and the macaque ventrolateralprefrontal cortex and corticocortical connectionpatterns in the monkey. Eur J Neurosci 2002,16:291-310.

6. Pandya DN, Seltzer B: Intrinsic connections and architectonicsof posterior parietal cortex in the rhesus monkey.J Comp Neurol 1982, 204:196-210.

7. Petrides M, Pandya DN: Projections to the frontal cortex fromthe posterior parietal region in the rhesus monkey.J Comp Neurol 1984, 228:105-116.

8. Goodale MS: Perceiving the world and grasping it:dissociations between conscious and unconscious visualprocessing. In The Cognitive Neurosciences. Edited byGazzaniga MS. MIT Press; 2004:1159-1172.

9.��

Sakagami M, Pan X, Uttl B: Behavioral inhibition and prefrontalcortex in decision-making. Neural Netw 2006,19:1255-1265.

In this review, the authors extensively discuss the different functions ofextended dorsal and extended ventral pathways in decision making. Theextended dorsal pathway makes decisions about motor actions in alargely autonomous and automatic fashion; the extended ventral pathwayis involved primarily in deliberate decisions and inhibitory control overbehavior.

10. Goldman-Rakic PS: Circuitry of primate prefrontal cortex andregulation of behavior by representational memory. InHandbook of Physiology: The Nervous System, vol V. Edited byPlum F. American Physiological Society; 1987:373-417.

11. Desimone R, Duncan J: Neural mechanisms of selective visualattention. Annu Rev Neurosci 1995, 18:193-222.

12. Fuster JM: The Prefrontal Cortex: Anatomy, Physiology, andNeurophysiology of the Frontal Lobe. Lippincott-Raven; 1997.

13. Miller EK: The prefrontal cortex and cognitive control.Nat Rev Neurosci 2000, 1:59-65.

14. Fuster JM, Alexander GE: Neuron activity related to short-termmemory. Science 1971, 173:652-654.

15. Kubota K, Niki H: Prefrontal cortical unit activity and delayedalternation performance in monkeys. J Neurophysiol 1971,34:337-347.

16. Goldman-Rakic PS: The prefrontal landscape: implications offunctional architecture for understanding human mentationand the central executive. Philos Trans R Soc Lond B Biol Sci1996, 351:1445-1453.

Current Opinion in Neurobiology 2007, 17:228–233

Page 5: Functional role of the ventrolateral prefrontal cortex in decision making

232 Cognitive neuroscience

17. Wilson FAW, Scalaidhe SPO, Goldman-Rakic PS: Dissociation ofobject and spatial processing domains in primate prefrontalcortex. Science 1993, 260:1955-1957.

18. Courtney SM, Ungerleider LG, Keil K, Haxby JV: Object andspatial visual working memory activate separate neuralsystems in human cortex. Cereb Cortex 1996, 6:39-49.

19. Rushworth MFS, Nixon PD, Eacott MJ, Passingham RE: Ventralprefrontal cortex is not essential for working memory.J Neurosci 1997, 17:4829-4838.

20. Owen Am: Stern CE, Look RB, Tracey I, Rosen BR, Petrides M:Functional organization of spatial and nonspatial workingmemory processing within the human lateral frontal cortex.Proc Natl Acad Sci USA 1998, 95:7721-7726.

21. Pasternak T, Greenlee MW: Working memory in primate sensorysystems. Nat Rev Neurosci 2005, 6:97-107.

22. Rushworth MFS, Buckley MJ, Gough PM, Alexander IH, Kyriazis D,McDonald KR, Passingham RE: Attentional selection and actionselection in the ventral and orbital prefrontal cortex.J Neurosci 2005, 25:11628-11636.

23. Zaksas D, Pasternak T: Directional signals in the prefrontalcortex and in area MT during a working memory for visualmotion task. J Neurosci 2006, 26:11726-11742.

24. Miyachi S, Lu X, Inoue S, Iwasaki T, Koike S, Nambu A, Takada M:Organization of multisynaptic inputs from prefrontal cortex toprimary motor cortex as revealed by retrograde transneuronaltransport of rabies virus. J Neurosci 2005, 25:2547-2556.

25. Watanabe M: Prefrontal unit activity during delayed conditionalgo/no-go discrimination in the monkey. 1. Relation to thestimulus. Brain Res 1986, 382:1-14.

26. Yajeya J, Quintana J, Fuster JM: Prefrontal representation ofstimulus attributes during delay tasks. 2. The role ofbehavioral significance. Brain Res 1988, 474:222-230.

27. Sakagami M, Niki H: Encoding of behavioral significance ofvisual stimuli by primate prefrontal neurons: relation torelevant task conditions. Exp Brain Res 1994, 97:423-436.

28. Sakagami M, Tsutsui K: The hierarchical organization ofdecision making in primate prefrontal cortex.Neurosci Res 1999, 34:79-89.

29. Lauwereyns J, Sakagami M, Tsutsui K, Kobayashi S, Koizumi M,Hikosaka O: Responses to task-irrelevant visual features byprimate prefrontal neurons. J Neurophysiol 2001, 86:2001-2010.

30. Lauwereyns J, Koizumi M, Sakagami M, Hikosaka O, Kobayashi S,Tsutsui K: Interference from irrelevant features on visualdiscrimination by macaques (Macaca fuscata): a behavioralanalogue of the human Stroop effect. J Exp Psychol Anim BehavProcess 2000, 26:352-357.

31. Hoshi E: Functional specialization within the dorsolateralprefrontal cortex: a review of anatomical and physiologicalstudies of non-human primates. Neurosci Res 2006,54:73-84.

32. Mansouri FA, Matsumoto K, Tanaka K: Prefrontal cell activitiesrelated to monkey’s success and failure in adapting to rulechanges in a Wisconsin Card Sorting Test analog.J Neurosci 2006, 26:2745-2756.

33. Freedman DJ, Riesenhuber M, Poggio T, Miller EK: Categoricalrepresentation of visual stimuli in the primate prefrontalcortex. Science 2001, 291:312-316.

34.��

Shima K, Isoda M, Mushiake H, Tanji J: Categorization ofbehavioural sequences in the prefrontal cortex. Nature 2007,445:315-318.

In this study, monkeys were trained to perform a series of four movementsin 11 different temporal orders that can be classified into three categories.The authors found that neurons in the LPFC represent a specific categoryof action sequences. The results indicate that the primate LPFC developsstructured knowledge of actions in order to adapt to complex environ-ments.

35. Ilinsky IA, Jouandet ML, Goldman-Rakic PS: Organization of thenigrothalamocortical system in the rhesus monkey.J Comp Neurol 1985, 2361:316-330.

Current Opinion in Neurobiology 2007, 17:228–233

36. Barbas H, De Olmos J: Projections from the amygdala tobasoventral and mediodorsal prefrontal regions in the rhesusmonkey. J Comp Neurol 1990, 300:549-571.

37. Tremblay L, Schultz W: Relative reward preference in primateorbitofrontal cortex. Nature 1999, 398:704-708.

38. Hikosaka K, Watanabe M: Long- and short-range rewardexpectancy in primate orbitofrontal cortex.Eur J Neurosci 2004, 19:1046-1054.

39. Paton JJ, Belova MA, Morrison SE, Salzman CD: The primateamygdala represents the positive and negative value of visualstimuli during learning. Nature 2006, 439:865-870.

40. Watanabe M: Reward expectancy in primate prefrontalneurons. Nature 1996, 382:629-632.

41. Watanabe M, Hikosaka K, Sakagami M, Shirakawa S: Coding andmonitoring of motivational context in the primate prefrontalcortex. J Neurosci 2002, 22:2391-2400.

42. Kobayashi S, Lauwereyns J, Koizumi M, Sakagami M, Hikosaka O:Influence of reward expectation on visuospatial processing inmacaque lateral prefrontal cortex. J Neurophysiol 2002,87:1488-1489.

43. Roesch MR, Olson CR: Impact of expected reward on neuronalactivity in prefrontal cortex, frontal and supplementary eyefields and premotor cortex. J Neurophysiol 2003,90:1766-1789.

44.��

Kobayashi S, Nomoto K, Watanabe M, Hikosaka O, Schultz W,Sakagami M: Influences of rewarding and aversive outcomeson activity in macaque lateral prefrontal cortex. Neuron 2006,51:861-870.

This is the first study to use aversive reinforcers in single-unit recordingsfrom the LPFC. The authors investigated how the LPFC represents andprocesses appetitive and aversive outcomes in a memory-guided sac-cade task with three different outcomes (liquid reward, avoidance of air-puff and sound only). LPFC neurons separately represented positive andaversive reinforcers, but the majority of neurons were modulated byreward. The results suggest that information about the two reinforcersis processed differentially in the LPFC.

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Kobayashi S, Kawagoe R, Takikawa Y, Koizumi M, Sakagami M,Hikosaka O: Functional differences between macaqueprefrontal cortex and caudate nucleus during eye movementswith and without reward. Exp Brain Res 2007, 176:341-355.

The prefrontal cortex and the basal ganglia have different roles in guidinggoal-directed behavior. To investigate these roles, neuronal activity wasrecorded from the LPFC and caudate nucleus in a memory-guidedsaccade task with an asymmetric reward schedule. LPFC neuronscommonly represented the cue direction, whereas caudate neuronsrepresented the reward-associated direction. The results suggest thatthe LPFC guides actions by external demands whereas the caudatenucleus selects actions by internally motivated states, and also thatthe LPFC is involved in long-term planning of reward whereas the caudateis involved in immediate reward.

46. Watanabe M, Hikosaka K, Sakagami M, Shirakawa S: Functionalsignificance of delay-period activity of primate prefrontalneurons in relation to spatial working memory and reward/omission-of-reward expectancy. Exp Brain Res 2005,166:263-276.

47. Pasupathy A, Miller EK: Different time courses of learning-related activity in the prefrontal cortex and striatum.Nature 2005, 433:873-876.

48. Ding L, Hikosaka O: Comparison of reward modulation in thefrontal eye field and caudate of the macaque. J Neurosci 2006,26:6695-6703.

49. McClure SM, Laibson DI, Loewenstein G, Cohen JD: Separateneural systems value immediate and delayed monetaryrewards. Science 2004, 306:503-507.

50. Tanaka SC, Doya K, Okoda G, Ueda K, Okamoto Y, Yamawaki S:Prediction of immediate and future rewards differentiallyrecruits cortico-basal ganglia loops. Nat Neurosci 2004,7:887-893.

51. Hikosaka O, Takikawa Y, Kawagoe R: Role of the basal ganglia inthe control of purposive saccadic eye movements.Physiol Rev 2000, 80:953-978.

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Functional role of the ventrolateral prefrontal cortex in decision making Sakagami and Pan 233

52. Barraclough DJ, Conroy ML, Lee D: Prefrontal cortex anddecision making in a mixed-strategy game. Nat Neurosci 2004,7:404-410.

53. Wallis JD, Anderson KC, Miller EK: Single neurons in prefrontalcortex encode abstract rules. Nature 2001, 411:953-956.

54. Sakai K, Passingham RE: Prefrontal interactions reflect futuretask operations. Nat Neurosci 2003, 6:75-81.

55. Bar M, Kassam KS, Ghuman AS, Boshyan J, Schmid AM, Dale AM,Hamalainen MS, Marinkovic K, Schacter DL, Rosen BR et al.:Top-down facilitation of visual recognition.Proc Natl Acad Sci USA 2006, 103:449-454.

56. Summerfield C, Egner T, Greene M, Koechlin E, Mangels J,Hirsch J: Predictive code for forthcoming perception in theprefrontal cortex. Science 2006, 314:1311-1314.

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Tsushima Y, Sasaki Y, Watanabe T: Greater disruption due tofailure of inhibitory control on an ambiguous subthresholddistractor. Science 2006, 314:1786-1788.

In this study, the authors show direct evidence that feedback from theLPFC to the visual cortex (area MT) signals to control activity in this areaand to modulate behavior. They found that a task-irrelevant subthresholdcoherent motion led to stronger disturbance in task performance than didsuprathreshold motion. With subthreshold motion, activity in the visualcortex was higher, but activity in the LPFC was lower, than with supra-threshold motion.

58. Sigala N, Logothetis NK: Visual categorization shapes featureselectivity in the primate temporal cortex. Nature 2002,414:318-320.

59. Tomita H, Ohbayashi M, Nakahara K, Hasegawa I, Miyashita Y:Top-down signal from prefrontal cortex in executive control ofmemory retrieval. Nature 1999, 401:699-703.

60. Webster MJ, Bachevalier J, Ungerleider LG: Connections ofinferior temporal areas TEO and TE with parietal and frontalcortex in macaque monkeys. Cereb Cortex 1994, 4:470-483.

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61. Manes F, Sahakian B, Clark L, Rogers R, Antoun N, Aitken M,Robbins T: Decision-making processes following damage tothe prefrontal cortex. Brain 2002, 125:624-639.

62. Aron AR, Robbins TW, Poldrack RA: Inhibition and the rightinferior frontal cortex. Trends Cogn Sci 2004, 8:170-177.

63. Levy R, Dubois B: Apathy and the functional anatomy of theprefrontal cortex-basal ganglia circuits. Cereb Cortex 2006,16:916-928.

64. Bunge SA, Dudukovic NM, Thomason ME, Vaidya CJ,Gabrieli JDE: Immature frontal lobe contributions to cognitivecontrol in children: evidence from fMRI. Neuron 2002,33:301-311.

65. Konishi S, Chikazoe J, Jimura K, Asari T, Miyashita Y: Neuralmechanism in anterior prefrontal cortex for inhibition ofprolonged set interference. Proc Natl Acad Sci USA 2005,102:12584-12588.

66. Sakagami M, Tsutsui K, Lauwereyns J, Koizumi M, Kobayashi S,Hikosaka O: A code of behavioral inhibition on the basis ofcolor, but not motion, in ventrolateral prefrontal cortex ofmacaque monkey. J Neurosci 2001, 21:4801-4808.

67. Hasegawa RP, Peterson BW, Goldberg ME: Prefrontal neuronscoding suppression of specific saccades. Neuron 2004,43:415-425.

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Johnston K, Everling S: Monkey dorsolateral prefrontal cortexsends task-selective signals directly to the superior colliculus.J Neurosci 2006, 26:12471-12478.

Activity in monkey DLPFC neurons was compared between the prosac-cade and antisaccade trials. The authors report that neurons projecting tothe superior colliculus selectively generated ‘stop signals’ in successfulantisaccade trials.

69. Romo R, Salinas E: Flutter discrimination: neural codes,perception, memory and decision making.Nat Rev Neurosci 2003, 4:203-218.

Current Opinion in Neurobiology 2007, 17:228–233