《认知神经科学》课程教学资源（参考文献）[Miller, E. K., & Cohen, J. D.（2001）]An integrative theory of prefrontal cortex function.

172 MILLER■COHEN of the world(C2).However,if you are in England(C3),you should look righ (R2).This is a classic example of a circumstance requiring cognitive control which we assume depends on the PFC.How does the PFC mediate the correct behavior? We assume that cues in the environment activate internal representations within 0 facti habitual or more salient)but produces the incorrect behavior.Thus,standing at the corner(C1),your"automatic"response would be to look left(RI).However,other cues in the environment"remind"you that you are in England(C3).That is,the cues activate the corresponding PFC representation,which includes information about the appropriate action.This produ activity along the pathway leading you to look right (e.g.CI that activation of this PFC representation is necessary for you to perform the correct behavior.That is,you had to keep"in mind"the knowledge that you were in England.You might even be able to cross a few streets correctly while keeping presentation antained nhorekel to revert to themore if this activity s tha is,ifyou you are in England tual response and look left.Repeated selection can strengthen the pathway from CI to R2 and allow it to become independent of the PFC.As this happens,the behavior becomes more automatic,so you can look right without having to keep in mind that you are in En gland.An rtant question is how the PFC develops the needed to prod repre sentations ce the contextually appropriate response In an unfamiliar situation you may try various behaviors to achieve a desired goal,perhaps starting with some that have been useful in a similar circumstance (looking to the left for oncoming traffic)and,if these fail,trying others until you meet with success (e.g.by looking right).We assume that each of these is as- iated with son patter of activity within the PFC(as in Figure )When a pattern of activity by strengthening connections between the PFC neurons acti vated by that behavior.This process also strengthens connections between these neurons and those whose activity represents the situation in which the behavior was useful,establishing an association between these circumstances and the PFC eated iterations the PFC representation can be further slaborated as subter combi and rep nations of events and contingencies between them and the requisite actions are learned.As is discussed below.brainstem neuromodulatory systems may provide the relevant reinforcement signals,allowing the system to"bootstrap"in this way Obviously,many details ed to he added hef we fully unders stand the c plexity of cognitive control.But we believe that this general notio can explair many of the posited functions of the PFC.The biasing influence of PFC feedback signals on sensory systems may mediate its role in directing attention(Stuss Benson 1986:Knight 1984,1997;Banich et al 2000),signals to the motor system

P1: FXZ January 12, 2001 14:38 Annual Reviews AR121-07 172 MILLER ¥ COHEN of the world (C2). However, if you are in England (C3), you should look right (R2). This is a classic example of a circumstance requiring cognitive control, which we assume depends on the PFC. How does the PFC mediate the correct behavior? We assume that cues in the environment activate internal representations within the PFC that can select the appropriate action. This is important when the course of action is uncertain, and especially if one of the alternatives is stronger (i.e. more habitual or more salient) but produces the incorrect behavior. Thus, standing at the corner (C1), your “automatic” response would be to look left (R1). However, other cues in the environment “remind” you that you are in England (C3). That is, the cues activate the corresponding PFC representation, which includes information about the appropriate action. This produces excitatory bias signals that guide neural activity along the pathway leading you to look right (e.g. C1 →···→ R2). Note that activation of this PFC representation is necessary for you to perform the correct behavior. That is, you had to keep “in mind” the knowledge that you were in England. You might even be able to cross a few streets correctly while keeping this knowledge in mind, that is, while activity of the appropriate representation is maintained in the PFC. However, if this activity subsides—that is, if you “forget” you are in England—you are likely to revert to the more habitual response and look left. Repeated selection can strengthen the pathway from C1 to R2 and allow it to become independent of the PFC. As this happens, the behavior becomes more automatic, so you can look right without having to keep in mind that you are in England. An important question is how the PFC develops the representations needed to produce the contextually appropriate response. In an unfamiliar situation you may try various behaviors to achieve a desired goal, perhaps starting with some that have been useful in a similar circumstance (looking to the left for oncoming traffic) and, if these fail, trying others until you meet with success (e.g. by looking right). We assume that each of these is as￾sociated with some pattern of activity within the PFC (as in Figure 2). When a behavior meets with success, reinforcement signals augment the corresponding pattern of activity by strengthening connections between the PFC neurons acti￾vated by that behavior. This process also strengthens connections between these neurons and those whose activity represents the situation in which the behavior was useful, establishing an association between these circumstances and the PFC pattern that supports the correct behavior. With time (and repeated iterations of this process), the PFC representation can be further elaborated as subtler combi￾nations of events and contingencies between them and the requisite actions are learned. As is discussed below, brainstem neuromodulatory systems may provide the relevant reinforcement signals, allowing the system to “bootstrap” in this way. Obviously, many details need to be added before we fully understand the com￾plexity of cognitive control. But we believe that this general notion can explain many of the posited functions of the PFC. The biasing influence of PFC feedback signals on sensory systems may mediate its role in directing attention (Stuss & Benson 1986; Knight 1984, 1997; Banich et al 2000), signals to the motor system Annu. Rev. Neurosci. 2001.24:167-202. Downloaded from arjournals.annualreviews.org by University of California - Los Angeles on 03/27/06. For personal use only

PREFRONTAL FUNCTION 173 may be responsible for response selection and inhibitory control (Fuster 1980. Diamond 1988),and signals to intermediate systems may support short-term (or working)memory (Goldman-Rakic 1987)and guide retrieval from long-term memory (Schachter 1997,Janowsky et al 1989,Gershberg Shimamura 1995). Wthou th PFC.the most used (and thus best established) eural path ways would predominate or,where these don'texist,behavior would be haphazard Such impulsive,inappropriate,or disorganized behavior is a hallmark of PFC dys- function in humans(e.g.Bianchi 1922,Duncan 1986,Luria 1969,Lhermitte 1983, Shallice Burgess 1996.Stuss Benson 1986). Minimal Requirements for a Mechanism of Top-Down Control There are several critical features of our theory.First,the PFC must provide a source of activity that can exert the required patter of biasing signals to other structures.We n thus think of PFC fund memory in the service of contre ol."It follows,theref e tha at the PF aintain its activity robustly against distractions until a goal is achieved,yet also be flexible enough to update its representations when needed.It must also house the appropriate representations, those that can select the neural pathways needed for the task.Insofar as primates are capable of tasks that involve diverse combinations of stimuli,internal states and respons ntations in the PFC must hav access to and be able to influence a similarly wide range of information in other brain regions.That is. PFC representations must have a high capacity for multimodality and integration Finally,as we can acquire new goals and means,the PFC must also exhibit a high degree of plasticity Of course.it must be possible to exhibit all these properties without the need to invoke some other mechanism of control to explain them,lest our theory be subject to perennial conc ns of a hidder nculus The rapidly accumulating body of findings regarding the PFC suggests that it meets these requirements.Fuster(1971,1973,1995),Goldman-Rakic(1987 1996),and others have extensively explored the ability of PFC neurons to main- tain task-relevant information.Miller et al(1996)have shown that this is robust to interferer e fron has lo eated the role of the PFCin integrating diverse ormation(Fuster 19 1995) The earliest de criptions c the effects of frontal lobe damage suggested its role in attention and the control of behavior(Ferrier 1876,Bianchi 1922),and investigators since have interpreted the pattern of deficits following pec damage as a loss of the ability to acquire and use rules (Shallice 1982.Duncan 1986.Passingham 1993,Grafmar 1994,Wise et al 1996).Recent empirical studies have begun identify correlates of plasticity in the PFC(Asaad et al 1998,Bichot et al 199,Schultz& Dickinson 2000),and recent computational studies suggest how these may operate as mechanisms for self-organization(Braver Cohen 2000,Egelman et al 1998) Our purpose in this article is to bring these various observations and arguments together,and to illustrate that a reaso coherent,and mechanistically explicit

P1: FXZ January 12, 2001 14:38 Annual Reviews AR121-07 PREFRONTAL FUNCTION 173 may be responsible for response selection and inhibitory control (Fuster 1980, Diamond 1988), and signals to intermediate systems may support short-term (or working) memory (Goldman-Rakic 1987) and guide retrieval from long-term memory (Schachter 1997, Janowsky et al 1989, Gershberg & Shimamura 1995). Without the PFC, the most frequently used (and thus best established) neural path￾ways would predominate or, where these don’t exist, behavior would be haphazard. Such impulsive, inappropriate, or disorganized behavior is a hallmark of PFC dys￾function in humans (e.g. Bianchi 1922, Duncan 1986, Luria 1969, Lhermitte 1983, Shallice & Burgess 1996, Stuss & Benson 1986). Minimal Requirements for a Mechanism of Top-Down Control There are several critical features of our theory. First, the PFC must provide a source of activity that can exert the required pattern of biasing signals to other structures. We can thus think of PFC function as “active memory in the service of control.” It follows, therefore, that the PFC must maintain its activity robustly against distractions until a goal is achieved, yet also be flexible enough to update its representations when needed. It must also house the appropriate representations, those that can select the neural pathways needed for the task. Insofar as primates are capable of tasks that involve diverse combinations of stimuli, internal states, and responses, representations in the PFC must have access to and be able to influence a similarly wide range of information in other brain regions. That is, PFC representations must have a high capacity for multimodality and integration. Finally, as we can acquire new goals and means, the PFC must also exhibit a high degree of plasticity. Of course, it must be possible to exhibit all these properties without the need to invoke some other mechanism of control to explain them, lest our theory be subject to perennial concerns of a hidden “homunculus.” The rapidly accumulating body of findings regarding the PFC suggests that it meets these requirements. Fuster (1971, 1973, 1995), Goldman-Rakic (1987, 1996), and others have extensively explored the ability of PFC neurons to main￾tain task-relevant information. Miller et al (1996) have shown that this is robust to interference from distraction. Fuster has long advocated the role of the PFC in integrating diverse information (Fuster 1985, 1995). The earliest descriptions of the effects of frontal lobe damage suggested its role in attention and the control of behavior (Ferrier 1876, Bianchi 1922), and investigators since have interpreted the pattern of deficits following PFC damage as a loss of the ability to acquire and use behavior-guiding rules (Shallice 1982, Duncan 1986, Passingham 1993, Grafman 1994, Wise et al 1996). Recent empirical studies have begun to identify neural correlates of plasticity in the PFC (Asaad et al 1998, Bichot et al 1996, Schultz & Dickinson 2000), and recent computational studies suggest how these may operate as mechanisms for self-organization (Braver & Cohen 2000, Egelman et al 1998). Our purpose in this article is to bring these various observations and arguments together, and to illustrate that a reasonably coherent, and mechanistically explicit, Annu. Rev. Neurosci. 2001.24:167-202. Downloaded from arjournals.annualreviews.org by University of California - Los Angeles on 03/27/06. For personal use only

174 MILLER■COHEN theory of PFC function is beginning to emerge.The view presented here draws on previous work that has begun to outline such a theory (e.g.Coh n Servan Schreiber 1992:Cohen et al 1996;O'Reilly et al 1999;Miller 1999,2000).In the sections that follow,we review neurobiological,neuropsychological,and neu- roimaging findings that support this theory,and computational modeling studies that have begun to make explicit the processing mechanisms involved. PROPERTIES OF THE PFC Convergence of Diverse Information One of the critical features for a system of cognitive control is the requirement that it have access to diverse information about both the internal state of the and the of the ord.The PFCs natomically well sit this requirement.The cytoarchitectonic areas that comprise the monkey PFC are often grouped into regional subdivisions,the orbital and medial,the lateral,and the mid-dorsal(see Figure 1).Collectively,these areas have interconnections with virtually all sensory systems,with cortical and subcortical motor system structures, and with limbic and midbrain structures involved in affect,me mory,and reward The subdivisions have partly unique,but overlapping.patterns of connections with the rest of the brain,which suggests some regional specialization.However,as in much of the neocortex many pFC connections are local there are extensive connections between different PFC areas that are likely to support an intermixing of di parate information.Such intermixing provides a basis for synthesizing results from,andc oordinating the regulation of ide variety ofbra s would be required of a brain area responsible Sensory Inputs The lateral and mid-dorsal PFC is more closely ass ociated with sensory neocortex than is the ventromedial PFC(see Figure 1).It receives visual somatosensory,and auditory information from the occipital,temporal,and pari etal cortices (Barbas Pandya 1989,1991;Goldman-Rakic Schwartz 1982 Pandya Barnes 1987:Pandya Yeterian 1990:Petrides Pandya 1984.1999: Pandya 199).Many PFC areas receive converging inputsfm two sen (Cha vis Pa 11970).Fo lethe(DL (areas8gana4 and(12级） PFC both receive projections from visual,auditory,and somatosensory cortex Furthermore,the PFC is connected with other cortical regions that are themselves sites of multimodal convergence.Many PFC areas (9,12,46,and 45)receive inputs from the ostral s mporal sulcus,which has n with bimoda or trimodal (visual,auditory,and somatosensory)responses (Br ce et al 1981 Pandya Barnes 1987).The arcuate sulcus region(areas 8 and 45)and area 12 seem to be particularly multimodal.They contain zones that receive overlapping inputs from three sensory modalities(Pandya Barnes 1987).In all these cases

P1: FXZ January 12, 2001 14:38 Annual Reviews AR121-07 174 MILLER ¥ COHEN theory of PFC function is beginning to emerge. The view presented here draws on previous work that has begun to outline such a theory (e.g. Cohen & Servan￾Schreiber 1992; Cohen et al 1996; O’Reilly et al 1999; Miller 1999, 2000). In the sections that follow, we review neurobiological, neuropsychological, and neu￾roimaging findings that support this theory, and computational modeling studies that have begun to make explicit the processing mechanisms involved. PROPERTIES OF THE PFC Convergence of Diverse Information One of the critical features for a system of cognitive control is the requirement that it have access to diverse information about both the internal state of the system and the external state of the world. The PFC is anatomically well situated to meet this requirement. The cytoarchitectonic areas that comprise the monkey PFC are often grouped into regional subdivisions, the orbital and medial, the lateral, and the mid-dorsal (see Figure 1). Collectively, these areas have interconnections with virtually all sensory systems, with cortical and subcortical motor system structures, and with limbic and midbrain structures involved in affect, memory, and reward. The subdivisions have partly unique, but overlapping, patterns of connections with the rest of the brain, which suggests some regional specialization. However, as in much of the neocortex, many PFC connections are local; there are extensive connections between different PFC areas that are likely to support an intermixing of disparate information. Such intermixing provides a basis for synthesizing results from, and coordinating the regulation of, a wide variety of brain processes, as would be required of a brain area responsible for the orchestration of complex behavior. Sensory Inputs The lateral and mid-dorsal PFC is more closely associated with sensory neocortex than is the ventromedial PFC (see Figure 1). It receives visual, somatosensory, and auditory information from the occipital, temporal, and pari￾etal cortices (Barbas & Pandya 1989, 1991; Goldman-Rakic & Schwartz 1982; Pandya & Barnes 1987; Pandya & Yeterian 1990; Petrides & Pandya 1984, 1999; Seltzer & Pandya 1989). Many PFC areas receive converging inputs from at least two sensory modalities (Chavis & Pandya 1976; Jones & Powell 1970). For ex￾ample, the dorsolateral (DL) (areas 8, 9, and 46) and ventrolateral (12 and 45) PFC both receive projections from visual, auditory, and somatosensory cortex. Furthermore, the PFC is connected with other cortical regions that are themselves sites of multimodal convergence. Many PFC areas (9, 12, 46, and 45) receive inputs from the rostral superior temporal sulcus, which has neurons with bimodal or trimodal (visual, auditory, and somatosensory) responses (Bruce et al 1981, Pandya & Barnes 1987). The arcuate sulcus region (areas 8 and 45) and area 12 seem to be particularly multimodal. They contain zones that receive overlapping inputs from three sensory modalities (Pandya & Barnes 1987). In all these cases, Annu. Rev. Neurosci. 2001.24:167-202. Downloaded from arjournals.annualreviews.org by University of California - Los Angeles on 03/27/06. For personal use only

PREFRONTAL FUNCTION 175 the PFC is directly connected with secondary or"association"but not primary sensory cortex. Motor Ouputs The dorsal PFC,particularly DL area 46,has preferential con nections with motor system structures that may be central to how the PFC exerts control over behavior.The DL area 46 is interconnected (a)with motor areas in the medial frontal lobe such as the supplementary motor area,the pre-supplementary motor area,and the rostral cingulate,(b)with the premotor cortex on the lateral and (c)with cerebellum olliculus(Bates&Goldm Rakic 193.GoldmanNauta 176.Lu.SchmahmannPandya 1997).The DL area 46 also sends projections to area 8,which contains the frontal eye fields,a region important for voluntary shifts of gaze.There are no direct connections between the PFC and primary motor cortex,but they are extensive with pre otor a eas that,in turn,send pr pjections to primary motor cortex and the spinal ord.Also mporant are the dense intercc be een the PFC and basal ganglia(Alexander et al 1986),a structure that is likely to be crucial for automating behavior.The basal ganglia receives inputs from much of the cerebral cortex,but its major output(via the thalamus)is frontal cortex(see Figure 1). Limbic Connections The orbital and medial PFC are closely associated with medial temporal limbic structures critical for long-term memory and the processing of internal states,such as affect and motivation.This includes direct and indirect (via the medial dorsal thalamus)connections with the hippocampus and associated ygdala,and theh P naral Price 1984.Barbas 990,Bar &Pandya 1989,Goldman-Rakic et al 1984,Porrino eta 1981,Van Hoesenetal 1972).Other PFCregions have access to these systems both through connections with the orbital and medial PFC and through other intervening structures. Intrinsic Connections Most PFC regions are interconnected with most other PFC regions.There are not only interconnections between all three major subdi- visions(ventromedial,lateral,and mid-dorsal)but also between their constituent areas (Barbas Pandva 1991 Pandva barnes 1987)The lateral pec is partic ularly well connected.Ventrolateral areas 12 and 45 are int nnected with DI well as with ventromedial areas and13 Intrinsic connections within the PFC allow information from regional afferents and processes to be distributed to other parts of the PFC.Thus,the PFC provides a venue by which information from wide-ranging brain systems can interact through relatively local circuitry Convergence and Plasticity Given that goal-directed behavior depends on our ability to piece together rela- tionships between a wide range of exte mal and internal information,it stands to

P1: FXZ January 12, 2001 14:38 Annual Reviews AR121-07 PREFRONTAL FUNCTION 175 the PFC is directly connected with secondary or “association” but not primary sensory cortex. Motor Outputs The dorsal PFC, particularly DL area 46, has preferential con￾nections with motor system structures that may be central to how the PFC exerts control over behavior. The DL area 46 is interconnected (a) with motor areas in the medial frontal lobe such as the supplementary motor area, the pre–supplementary motor area, and the rostral cingulate, (b) with the premotor cortex on the lateral frontal lobe, and (c) with cerebellum and superior colliculus (Bates & Goldman￾Rakic 1993, Goldman & Nauta 1976, Lu et al 1994, Schmahmann & Pandya 1997). The DL area 46 also sends projections to area 8, which contains the frontal eye fields, a region important for voluntary shifts of gaze. There are no direct connections between the PFC and primary motor cortex, but they are extensive with premotor areas that, in turn, send projections to primary motor cortex and the spinal cord. Also important are the dense interconnections between the PFC and basal ganglia (Alexander et al 1986), a structure that is likely to be crucial for automating behavior. The basal ganglia receives inputs from much of the cerebral cortex, but its major output (via the thalamus) is frontal cortex (see Figure 1). Limbic Connections The orbital and medial PFC are closely associated with medial temporal limbic structures critical for long-term memory and the processing of internal states, such as affect and motivation. This includes direct and indirect (via the medial dorsal thalamus) connections with the hippocampus and associated neocortex, the amygdala, and the hypothalamus (Amaral & Price 1984, Barbas & De Olmos 1990, Barbas & Pandya 1989, Goldman-Rakic et al 1984, Porrino et al 1981, Van Hoesen et al 1972). Other PFC regions have access to these systems both through connections with the orbital and medial PFC and through other intervening structures. Intrinsic Connections Most PFC regions are interconnected with most other PFC regions. There are not only interconnections between all three major subdi￾visions (ventromedial, lateral, and mid-dorsal) but also between their constituent areas (Barbas & Pandya 1991, Pandya & Barnes 1987). The lateral PFC is partic￾ularly well connected. Ventrolateral areas 12 and 45 are interconnected with DL areas 46 and 8, with dorsal area 9, as well as with ventromedial areas 11 and 13. Intrinsic connections within the PFC allow information from regional afferents and processes to be distributed to other parts of the PFC. Thus, the PFC provides a venue by which information from wide-ranging brain systems can interact through relatively local circuitry. Convergence and Plasticity Given that goal-directed behavior depends on our ability to piece together rela￾tionships between a wide range of external and internal information, it stands to Annu. Rev. Neurosci. 2001.24:167-202. Downloaded from arjournals.annualreviews.org by University of California - Los Angeles on 03/27/06. For personal use only

176 MILLER■COHEN reason that top-down control must come from PFC representations that reflect a wide range of learned associations. There is mounting neurophysiological evi dence that this is the case.Asaad et al (1998)trained monkeys to associate,on different blocks of trials,each of two cue objects with a saccade to the right or a saccade to the left They found relatively few lateral pe neurons whose activity ween a visual cue and a directional saccade it instructed.For example,a given cell might only be strongly activated when object“A”instructed“saccade left”and not when object“B”instructed the same saccade or when object“A”instructed another sac cade(Figure 3A).Lateral PFC neurons can also convey the degree of association between a cue e and a response(Quintana&Fuster 1992) Other studies indicate that PFC neurons acquire selectivity for features to which they are initially insensitive but are behaviorally relevant.For example,Bichot etal(1996)observed that neurons in the frontal eye fields(in the bow of the arcuate sulcusordinarily not selective to the form and color ofstimuli-became so as the animal learned eye movements that were contingent on these features.Similarly Watanabe(1990 1992)ha ed monkeys to recogn that certa visual and auditory stimuli signaled whether or not,on different trials,a reward(a drop of juice)would be delivered.He found that neurons in lateral PFC(around the arcuate sulcus and posterior end of the principal sulcus)came to reflect specific cue-reward associations.For example,a given neuron could show strong activation to one of the two auditory (and the visual)cu signaled Other neuror strongly modulated by their reward status. More complicated behaviors depend not on simple contingencies between cues and responses or rewards but on general principles or rules that may involve more. complex mapping.PFC activity also seems to represent this information.Barone oseph(199)observed cells near the arcuate sulcus that were responsive to spe cific light stimuli,but only when they occurred at a particular point in a particular Figure 3 ()Shown is the activity of four single prefrontal (PF)neurons when each of two objects,on different trials,instructed either a saccade to the right or a saccade to the left The lines connect the average values obtained when a given object cued one or the other saccade.The error bars show the standard error of the mean.Note that in each case,the neuron's activity depends on both the cue object and the saccade direction and that the tuning is nonlinear or conjunctive.That is,the level of activity to a given combination of object and saccade cannot be predicted from the neuron's response to the other combinations [Adapted from Asaad et al(1998).](B)A PF neuron whose neural response to a cue object was highly dependent on task context.The bottom half shows an example of a single PF neuron's response to the same cue object during an object task(delayed matching to sample)and during an associative task(conditional visual motor).Note that the neuron is responsive to the cue during one task but not during the other,even though sensory stimulation is identical across the tasks.[Adapted from Asaad et al (2000).]

P1: FXZ January 12, 2001 14:38 Annual Reviews AR121-07 176 MILLER ¥ COHEN reason that top-down control must come from PFC representations that reflect a wide range of learned associations. There is mounting neurophysiological evi￾dence that this is the case. Asaad et al (1998) trained monkeys to associate, on different blocks of trials, each of two cue objects with a saccade to the right or a saccade to the left. They found relatively few lateral PF neurons whose activity simply reflected a cue or response. Instead, the modal group of neurons (44% of the population) showed activity that reflected the current association between a visual cue and a directional saccade it instructed. For example, a given cell might only be strongly activated when object “A” instructed “saccade left” and not when object “B” instructed the same saccade or when object “A” instructed another sac￾cade (Figure 3A). Lateral PFC neurons can also convey the degree of association between a cue and a response (Quintana & Fuster 1992). Other studies indicate that PFC neurons acquire selectivity for features to which they are initially insensitive but are behaviorally relevant. For example, Bichot et al (1996) observed that neurons in the frontal eye fields (in the bow of the arcuate sulcus)—ordinarily not selective to the form and color of stimuli—became so as the animal learned eye movements that were contingent on these features. Similarly, Watanabe (1990, 1992) has trained monkeys to recognize that certain visual and auditory stimuli signaled whether or not, on different trials, a reward (a drop of juice) would be delivered. He found that neurons in lateral PFC (around the arcuate sulcus and posterior end of the principal sulcus) came to reflect specific cue-reward associations. For example, a given neuron could show strong activation to one of the two auditory (and none of the visual) cues, but only when it signaled reward. Other neurons were bimodal, activated by both visual and auditory cues but also strongly modulated by their reward status. More complicated behaviors depend not on simple contingencies between cues and responses or rewards but on general principles or rules that may involve more￾complex mapping. PFC activity also seems to represent this information. Barone & Joseph (1989) observed cells near the arcuate sulcus that were responsive to spe￾cific light stimuli, but only when they occurred at a particular point in a particular −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−→ Figure 3 (A) Shown is the activity of four single prefrontal (PF) neurons when each of two objects, on different trials, instructed either a saccade to the right or a saccade to the left. The lines connect the average values obtained when a given object cued one or the other saccade. The error bars show the standard error of the mean. Note that in each case, the neuron’s activity depends on both the cue object and the saccade direction and that the tuning is nonlinear or conjunctive. That is, the level of activity to a given combination of object and saccade cannot be predicted from the neuron’s response to the other combinations. [Adapted from Asaad et al (1998).] (B) A PF neuron whose neural response to a cue object was highly dependent on task context. The bottom half shows an example of a single PF neuron’s response to the same cue object during an object task (delayed matching to sample) and during an associative task (conditional visual motor). Note that the neuron is responsive to the cue during one task but not during the other, even though sensory stimulation is identical across the tasks. [Adapted from Asaad et al (2000).] Annu. Rev. Neurosci. 2001.24:167-202. Downloaded from arjournals.annualreviews.org by University of California - Los Angeles on 03/27/06. For personal use only