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