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Functional role of the ventrolateral prefrontal cortex in decision making
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 consideration 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 inferotemporal 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 transform 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 revealing the mechanisms that underlie decision making in the extended ventral pathway, and in particular the functional roles of the VLPFC.
Ventrolateral prefrontal cortex and behavioral significance The lateral prefrontal cortex (LPFC) is thought to contribute 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 GoldmanRakic 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 supported 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 www.sciencedirect.com
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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 execution 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 discriminated 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 structure 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 motivational information Our 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 rewardmodulation 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 asymmetric 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 www.sciencedirect.com
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 punishment 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 condition 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 integration is not yet completed at the LPFC stage of information 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 rewardanticipating 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
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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 information. 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 considering the changeable strategy of an enemy (a computer); 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 representations [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 planning. Such integration of information could enable elaborate decisions to be made with respect to goal-directed behavior in complex circumstances.
Functional roles of the VLPFC in decision making How 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 information must include behavioral significance, sensory areas can utilize this information to improve their descriptions of circumstances that are relevant to goal-directed behavior. Representation of an object in the inferotemporal 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 interconnections within posterior cortices [60]; these connections 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 activation in the VLPFC [64,65]. Single-unit recording experiments also supported this notion [66,67,68]. Sakagami 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 goindicating colors than to no-go colors in the color condition. 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-irrelevant 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.
Conclusion The 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 computes adaptive codes on the basis of behavioral significance, which leads to deliberate decision making or goaldirected 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 significance can be carried to other areas (black lines). Through www.sciencedirect.com
Functional role of the ventrolateral prefrontal cortex in decision making Sakagami and Pan 231
Figure 1
Acknowledgement We thank J Lauwereyns for critical comments. Our work is supported by the Human Frontier Science Program (MS), by Precursory Research for Embryonic Science and Technology (MS), and by Grant-in-Aid for Scientific Research on Priority Areas (MS) and Tamagawa University COE (MS) from the Japanese Ministry of Education, Science, Sports and Culture.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: of special interest of outstanding interest
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 descriptions 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 mechanisms that generate and organize behavioral significance 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
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Current Opinion in Neurobiology 2007, 17:228–233
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 consideration 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 inferotemporal 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 transform 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 revealing the mechanisms that underlie decision making in the extended ventral pathway, and in particular the functional roles of the VLPFC.
Ventrolateral prefrontal cortex and behavioral significance The lateral prefrontal cortex (LPFC) is thought to contribute 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 GoldmanRakic 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 supported 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 www.sciencedirect.com
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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 execution 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 discriminated 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 structure 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 motivational information Our 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 rewardmodulation 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 asymmetric 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 www.sciencedirect.com
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 punishment 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 condition 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 integration is not yet completed at the LPFC stage of information 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 rewardanticipating 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
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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 information. 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 considering the changeable strategy of an enemy (a computer); 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 representations [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 planning. Such integration of information could enable elaborate decisions to be made with respect to goal-directed behavior in complex circumstances.
Functional roles of the VLPFC in decision making How 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 information must include behavioral significance, sensory areas can utilize this information to improve their descriptions of circumstances that are relevant to goal-directed behavior. Representation of an object in the inferotemporal 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 interconnections within posterior cortices [60]; these connections 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 activation in the VLPFC [64,65]. Single-unit recording experiments also supported this notion [66,67,68]. Sakagami 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 goindicating colors than to no-go colors in the color condition. 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-irrelevant 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.
Conclusion The 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 computes adaptive codes on the basis of behavioral significance, which leads to deliberate decision making or goaldirected 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 significance can be carried to other areas (black lines). Through www.sciencedirect.com
Functional role of the ventrolateral prefrontal cortex in decision making Sakagami and Pan 231
Figure 1
Acknowledgement We thank J Lauwereyns for critical comments. Our work is supported by the Human Frontier Science Program (MS), by Precursory Research for Embryonic Science and Technology (MS), and by Grant-in-Aid for Scientific Research on Priority Areas (MS) and Tamagawa University COE (MS) from the Japanese Ministry of Education, Science, Sports and Culture.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: of special interest of outstanding interest
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 descriptions 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 mechanisms that generate and organize behavioral significance 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
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