178 MILLER■COHEN sequence that the monkey had to imitate.White&Wise(1999)trained a monkey to orient to a visual target according to two different rules.One of four cue patterns briefly appeared at one of four locations.The cue indicated where a target would eventually appear.It did so by one of two rules,aspatial rule(the cue appeared at the same location that the target would appear)or anassociative rule(the identity ofthe ue instructed the locatio to昌Crshow rule.Another example was provided by Asaad et al(2000),who trained monkeys to alternate between tasks that employed the same cues and responses but three different rules:matching(delayed matching to sample),associative(conditional visuomotor),and spatial (spatial delayed response).Over half of lateral PFC neurons were rule dependen Neur de ofen depended on which uleurntu coming the baseline activity of many neurons(54%)varied with the rule.Hoshiet al(1998) have also observed PFC neurons that were modulated by whether the monkey was using a shape-matching or location-matching rule.Recently.Wallis et al (2000) have shown that lateral and orbitofrontal PFC neurons reflect whether the monkey Sui of onkeysand umh PPC is currently using a"matc ing”or"nonma critical for learning rules.For example.Petrides found that following PFC damage patients could no longer learn arbitrary associations between visual patterns and hand gestures (Petrides 1985,1990).In monkeys,damage to ventrolateral area 12 or to the arcuate sulcus region also imp rs the abi response associations(Halsband d&Passingham 1985,Mu des 1982,1985).Leaming of visual stimulus-response conditional associations is also impaired by damage to PFC inputs from the temporal cortex(Eacott Gaffan 1992 Gaffan Harrison 1988,Parker Gaffan 1998).Passingham(1993)argues that most,ifnot all,tasks that are disrupted following PFC damage depend onacquiring conditional associations(if-the en rules). In sum,these results indicate that PFC neural activity represents the rules or mappings required to perform a particular task,and not just single stimuli or forthcoming actions.We assume that this activity within the PFC establishes these mappings by biasing competition in other parts of the brain responsible for actually perforn the task.These sigals favor task-relevant sensory inputs(). Feedback to Other Brain Areas provide these feedback signals;it sends projections to much of the neocortex (Pandya Barnes 1987,Pandya Yeterian 1990).Physiological studies have yielded results consistent with this notion.P1: FXZ January 12, 2001 14:38 Annual Reviews AR121-07 178 MILLER ¥ COHEN sequence that the monkey had to imitate. White & Wise (1999) trained a monkey to orient to a visual target according to two different rules. One of four cue patterns briefly appeared at one of four locations. The cue indicated where a target would eventually appear. It did so by one of two rules, a spatial rule (the cue appeared at the same location that the target would appear) or an associative rule (the identity of the cue instructed the location, e.g. cue A indicated the right, cue B the left, etc). They found that up to half of lateral PFC neurons showed activity that varied with the rule. Another example was provided by Asaad et al (2000), who trained monkeys to alternate between tasks that employed the same cues and responses but three different rules: matching (delayed matching to sample), associative (conditional visuomotor), and spatial (spatial delayed response). Over half of lateral PFC neurons were rule dependent. Neural responses to a given cue or forthcoming saccade often depended on which rule was current in the task (Figure 3B). Plus, the baseline activity of many neurons (54%) varied with the rule. Hoshi et al (1998) have also observed PFC neurons that were modulated by whether the monkey was using a shape-matching or location-matching rule. Recently, Wallis et al (2000) have shown that lateral and orbitofrontal PFC neurons reflect whether the monkey is currently using a “matching” or “nonmatching” rule to select a test object. Studies of monkeys and humans with PFC damage also suggest that the PFC is critical for learning rules. For example, Petrides found that following PFC damage, patients could no longer learn arbitrary associations between visual patterns and hand gestures (Petrides 1985, 1990). In monkeys, damage to ventrolateral area 12 or to the arcuate sulcus region also impairs the ability to learn arbitrary cue￾response associations (Halsband & Passingham 1985, Murray et al 2000, Petrides 1982, 1985). Learning of visual stimulus-response conditional associations is also impaired by damage to PFC inputs from the temporal cortex (Eacott & Gaffan 1992, Gaffan & Harrison 1988, Parker & Gaffan 1998). Passingham (1993) argues that most, if not all, tasks that are disrupted following PFC damage depend on acquiring conditional associations (if-then rules). In sum, these results indicate that PFC neural activity represents the rules, or mappings required to perform a particular task, and not just single stimuli or forthcoming actions. We assume that this activity within the PFC establishes these mappings by biasing competition in other parts of the brain responsible for actually performing the task. These signals favor task-relevant sensory inputs (attention), memories (recall), and motor outputs (response selection) and thus guide activity along the pathways that connect them (conditional association). Feedback to Other Brain Areas Our model of PFC function requires feedback signals from the PFC to reach widespread targets throughout the brain. The PFC has the neural machinery to provide these feedback signals; it sends projections to much of the neocortex (Pandya & Barnes 1987, Pandya & Yeterian 1990). Physiological studies have yielded results consistent with this notion. 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