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. 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