Abstract
One of the enduring mysteries of brain function concerns the process of cognitive control. How does complex and seemingly wilful behaviour emerge from interactions between millions of neurons? This has long been suspected to depend on the prefrontal cortex — the neocortex at the anterior end of the brain — but now we are beginning to uncover its neural basis. Nearly all intended behaviour is learned and so depends on a cognitive system that can acquire and implement the ‘rules of the game’ needed to achieve a given goal in a given situation. Studies indicate that the prefrontal cortex is central in this process. It provides an infrastructure for synthesizing a diverse range of information that lays the foundation for the complex forms of behaviour observed in primates.
Key Points
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The prefrontal cortex is important for cognitive control, the ability to orchestrate brain processes along a common theme.
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Neurophysiological and behavioural studies indicate that prefrontal neurons may participate in neural ensembles that represent task contingencies and rules.
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The formation of task representations in the prefrontal cortex may depend on midbrain dopamine neurons that signal when plasticity should occur.
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Prefrontal neurons can hold information ‘online’ temporarily. This is critical for bridging temporal gaps between events, actions and consequences, and for resisting distractions.
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Prefrontal task representations provide bias signals to other brain structures to guide the flow of activity along task-relevant pathways.
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With practice, task-relevant pathways can be established in the posterior neocortex independently of the prefrontal cortex.
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This theory of prefrontal function complements and extends previous theories. It suggests mechanisms that provide a foundation for the complex forms of behaviour observed in primates.
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References
Barsalou, L. W. & Sewell, D. R. Contrasting the representation of scripts and categories. J. Mem. Lang. 24, 646–665 (1985).
Abbott, V., Black, J. B. & Smith, E. E. The representation of scripts in memory. J. Mem. Lang. 24, 179–199 (1985).
Norman, D. A. & Shallice, T. in Consciousness and Self–Regulation: Advances in Research and Theory (eds Davidson, R. J., Schwartz, G. E. & Shapiro, D.) 1–18 (Plenum, New York, 1986).
Grafman, J. in Handbook of Neuropsychology (eds Boller, F. & Grafman, J.) 187 (Elsevier, Amsterdam, 1994).
Cohen, J. D. & Servan-Schreiber, D. Context, cortex, and dopamine: A connectionist approach to behavior and biology in schizophrenia. Psychol. Rev. 99, 45–77 (1992).An account of how task ‘context’ representations can be implemented in a model of cognitive control that further proposes that dopamine may be central in this process.
Passingham, R. The Frontal Lobes and Voluntary Action (Oxford Univ. Press, Oxford, 1993).
Wise, S. P., Murray, E. A. & Gerfen, C. R. The frontal-basal ganglia system in primates. Crit. Rev. Neurobiol. 10, 317–356 (1996).
Miller, E. K. The prefrontal cortex: complex neural properties for complex behavior. Neuron 22, 15–17 ( 1999).
Pandya, D. N. & Barnes, C. L. in The Frontal Lobes Revisited (ed. Perecman, E.) 41–72 (IRBN Press, New York, 1987).
Goldman-Rakic, P. S. in Handbook of Physiology: The Nervous System (ed. Plum, F.) 373–417 (American Physiological Society, Bethesda, 1987).
Fuster, J. M. The Prefrontal Cortex (Raven Press, New York, 1989).
Barbas, H. & Pandya, D. in Frontal Lobe Function and Dysfunction (eds Levin, H. S., Eisenberg, H. M. & Benton, A. L.) 35– 58 (Oxford Univ. Press, New York, 1991).
Dehaere, S. & Changeux, J. P. The Wisconsin Card Sort Test: Theoretical analysis and modelling in a neuronal network. Cerebral Cortex 1, 62–79 ( 1991).
Cohen, J. D., Dunbar, K. & McClelland, J. L. On the control of automatic processes: A parallel distributed processing model of the Stroop effect. Psychol. Rev. 97, 332–361 ( 1996).
Shimamura, A. P. The role of the prefrontal cortex in dynamic filtering. Psychobiology (in the press).
Dickinson, A. Contemporary Animal Learning Theory (Cambridge Univ. Press, 1980).
Vaadia, E., Benson, D. A., Hienz, R. D. & Goldstein, M. H. Jr Unit study of monkey frontal cortex: active localization of auditory and of visual stimuli. J. Neurophysiol. 56, 934–952 (1986).
Watanabe, M. Frontal units of the monkey coding the associative significance of visual and auditory stimuli. Exp. Brain Res. 89, 233–247 (1992).
Rao, S. C., Rainer, G. & Miller, E. K. Integration of what and where in the primate prefrontal cortex. Science 276, 821– 824 (1997).
Rainer, G., Asaad, W. F. & Miller, E. K. Memory fields of neurons in the primate prefrontal cortex. Proc. Natl Acad. Sci. USA 95, 15008 –15013 (1998).
White, I. M. & Wise, S. P. Rule-dependent neuronal activity in the prefrontal cortex. Exp. Brain Res. 126, 315–335 (1999).Demonstration of ‘rule-tuned’ neurons in the primate prefrontal cortex. Monkeys were trained to acquire a target using either a ‘spatial’ or ‘associative’ rule.
Rainer, G., Asaad, W. F. & Miller, E. K. Selective representation of relevant information by neurons in the primate prefrontal cortex. Nature 393, 577–579 (1998).
Petrides, M. Deficits in non-spatial conditional associative learning after periarcuate lesions in the monkey. Behav. Brain Res. 16, 95–101 (1985).
Petrides, M. Nonspatial conditional learning impaired in patients with unilateral frontal but not unilateral temporal lobe excisions. Neuropsychologia 28, 137–149 (1990).
Gaffan, D. & Harrison, S. Inferotemporal-frontal disconnection and fornix transection in visuomotor conditional learning by monkeys. Behav. Brain Res. 31, 149–163 (1988).
Eacott, M. J. & Gaffan, D. Inferotemporal-frontal disconnection — the uncinate fascicle and visual associative learning in monkeys. Eur. J. Neurosci. 4, 1320–1332 (1992).
Parker, A. & Gaffan, D. Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions. Neuropsychologia 36, 259 –271 (1998).
Watanabe, M. Prefrontal unit activity during associative learning in the monkey. Exp. Brain Res. 80, 296–309 (1990).
Asaad, W. F., Rainer, G. & Miller, E. K. Neural activity in the primate prefrontal cortex during associative learning. Neuron 21, 1399–1407 (1998). Neural information about a cue object and the saccade it instructed merged together in prefrontal activity in this neurophysiological study of associative learning.
Fuster, J. M., Bodner, M. & Kroger, J. K. Cross-modal and cross-temporal association in neurons of frontal cortex. Nature 405, 347– 351 (2000).Demonstration that prefrontal neurons reflect learned cross-modal associations. Many prefrontal neurons were selectively responsive to a visual stimulus and the auditory stimulus with which it was associated.
Bichot, N. P., Schall, J. D. & Thompson, K. G. Visual feature selectivity in frontal eye fields induced by experience in mature macaques. Nature 381 , 697–699 (1996). Neurophysiological study showing learning-induced response properties for neurons in the frontal eye fields. Monkeys trained to look for a particular colour developed neurons sensitive to that colour.
Bichot, N. P. & Schall, J. D. Effects of similarity and history on neural mechanisms of visual selection. Nature Neurosci. 2, 549–554 (1999).
Hoshi, E., Shima, K. & Tanji, J. Task-dependent selectivity of movement-related neuronal activity in the primate prefrontal cortex. J. Neurophysiol. 80, 3392–3397 (1998).
Asaad, W. F., Rainer, G. & Miller, E. K. Task-specific neural activity in the primate prefrontal cortex. J. Neurophysiol. 84, 451– 459 (2000).Demonstration that the responses of prefrontal neurons to cues and actions are highly task-specific. This indicates that prefrontal neurons may participate in neural ensembles that represent tasks, not just stimuli and forthcoming motor acts.
Wallis, J. D., Anderson, K. C. & Miller, E. K. Neuronal representation of abstract rules in the orbital and lateral prefrontal cortices (PFC). Soc. Neurosci. Abstr. (in the press).
Dehaene, S., Kerszeberg, M. & Changeux, J. P. A neuronal model of a global workspace in effortful cognitive tasks. Proc. Natl Acad. Sci. USA 95, 14529–14534 (1998).
Watanabe, M. Reward expectancy in primate prefrontal neurons. Nature 382, 629–632 (1996).
Tremblay, L. & Schultz, W. Relative reward preference in primate orbitofrontal cortex. Nature 398, 704– 708 (1999).
Leon, M. I. & Shadlen, M. N. Effect of expected reward magnitude on the response of neurons in the dorsolateral prefrontal cortex of the macaque . Neuron 24, 415–425 (1999).
Mirenowicz, J. & Schultz, W. Importance of unpredictability for reward responses in primate dopamine neurons. J. Neurophysiol. 72, 1024–1027 (1994).
Mirenowicz, J. & Schultz, W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379, 449–451 ( 1996).
Schultz, W., Apicella, P. & Ljungberg, T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913 (1993).
Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27 (1998 ).
Hollerman, J. R. & Schultz, W. Dopamine neurons report an error in the temporal prediction of reward during learning. Nature Neurosci. 1, 304–309 (1998).
Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473– 500 (2000).A review of evidence that dopamine neurons provide a ‘prediction error’ signal that can orchestrate learning of the means to acquire rewards.
Cepeda, C., Buchwald, N. A. & Levine, M. S. Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated. Proc. Natl Acad. Sci. USA 90, 9576– 9580 (1993).
Williams, G. V. & Goldman-Rakic, P. S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376, 572–575 ( 1995).
Braver, T. S. & Cohen, J. D. in Attention and Performance 18 (eds Monsell, S. & Driver, J.) (MIT Press, Cambridge, Massachusetts, in the press).
Fuster, J. M. Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory. J. Neurophysiol. 36 , 61–78 (1973).
Niki, H. Differential activity of prefrontal units during right and left delayed response trials. Brain Res. 70, 346– 349 (1974).
Funahashi, S., Bruce, C. J. & Goldman-Rakic, P. S. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J. Neurophysiol. 61, 331–349 (1989).
Miller, E. K., Erickson, C. A. & Desimone, R. Neural mechanisms of visual working memory in prefrontal cortex of the macaque. J. Neurosci. 16, 5154–5167 (1996).
Romo, R., Brody, C. D., Hernandez, A. & Lemus, L. Neuronal correlates of parametric working memory in the prefrontal cortex . Nature 399, 470–473 (1999).
Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 ( 1997).
Duncan, J., Emslie, H., Williams, P., Johnson, R. & Freer, C. Intelligence and the frontal lobe: The organization of goal-directed behavior. Cogn. Psychol. 30, 257–303 (1996).
Miller, E. K., Li, L. & Desimone, R. Activity of neurons in anterior inferior temporal cortex during a short-term memory task. J. Neurosci. 13, 1460–1478 (1993).
Constantinidis, C. & Steinmetz, M. A. Neuronal activity in posterior parietal area 7a during the delay periods of a spatial memory task. J. Neurophysiol. 76, 1352– 1355 (1996).
Zipser, D., Kehoe, B., Littlewort, G. & Fuster, J. A spiking network model of short-term active memory. J. Neurosci. 13, 3406–3420 ( 1993).
Durstewitz, D., Kelc, M. & Gunturkun, O. A neurocomputational theory of the dopaminergic modulation of working memory functions. J. Neurosci. 19, 2807–2822 (1999).
Wang, X. J. Synaptic basis of cortical persistent activity: the importance of NMDA receptors to working memory. J. Neurosci. 19, 9587 –9603 (1999).
Durstewitz, D., Seamans, J. K. & Sejnowski, T. J. Dopamine-mediated stabilization of delay-period activity in a network model of the prefrontal cortex. J. Neurophysiol. 83, 1733–1750 (2000).
Desimone, R. & Duncan, J. Neural mechanisms of selective visual attention. Ann. Rev. Neurosci. 18, 193– 222 (1995).A review of the neural mechanisms for focal attention. The authors suggest that bias signals from the PFC resolve neural competition between items vying to reach awareness.
Miller, E. K. in Attention and Performance 18 (eds Monsell, S. & Driver, J.) (MIT Press, Cambridge, Massachusetts, in the press).
Fuster, J. M., Bauer, R. H. & Jervey, J. P. Functional interactions between inferotemporal and prefrontal cortex in a cognitive task. Brain Res. 330 , 299–307 (1985).
Chafee, M. V. & Goldman-Rakic, P. S. Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades. J. Neurophysiol. 83, 1550– 1566 (2000).
Tomita, H., Ohbayashi, M., Nakahara, K., Hasegawa, I. & Miyashita, Y. Top-down signal from prefrontal cortex in executive control of memory retrieval. Nature 401, 699–703 (1999). Neurophysiological study showing that ‘top-down’ signals from the PFC are required to activate long-term memories stored in the inferior temporal cortex.
Miller, E. K. & Desimone, R. Parallel neuronal mechanisms for short-term memory. Science 263, 520– 522 (1994).
Recanzone, G. H., Merzenich, M. M. & Jenkins, W. M. Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a. J. Neurophysiol. 67, 1057– 1070 (1992).
Merzenich, M. M. & Sameshima, K. Cortical plasticity and memory. Curr. Opin. Neurobiol. 3, 187 –196 (1993).
Gilbert, C. D. Plasticity in visual perception and physiology. Curr. Opin. Neurobiol. 6, 269–274 ( 1996).
Rushworth, M. F., Nixon, P. D., Eacott, M. J. & Passingham, R. E. Ventral prefrontal cortex is not essential for working memory. J. Neurosci. 17, 4829–4838 (1997).
Knight, R. T. Decreased response to novel stimuli after prefrontal lesions in man. Clin. Neurophys. 59, 9–20 (1984).
Yamaguchi, S. & Knight, R. T. Anterior and posterior association cortex contributions to the somatosensory P300. J. Neurosci. 11, 2039–2054 (1991).
Knight, R. T. Distributed cortical network for visual attention. J. Cogn. Neurosci. 9, 75–91 (1997 ).
Shadmehr, R. & Holcomb, H. Neural correlates of motor memory consolidation. Science 277, 821– 824 (1997).
Riches, I. P., Wilson, F. A. & Brown, M. W. The effects of visual stimulation and memory on neurons of the hippocampal formation and the neighboring parahippocampal gyrus and inferior temporal cortex of the primate. J. Neurosci. 11, 1763–1779 (1991).
Miller, E. K., Gochin, P. M. & Gross, C. G. Habituation-like decrease in the responses of neurons in inferior temporal cortex of the macaque. Vis. Neurosci. 7, 357–362 (1991).
Li, L., Miller, E. K. & Desimone, R. The representation of stimulus familiarity in anterior inferior temporal cortex. J. Neurophysiol. 69, 1918–1929 (1993).
Miller, E. K., Li, L. & Desimone, R. A neural mechanism for working and recognition memory in inferior temporal cortex. Science 254, 1377–1379 (1991).
Rainer, G., Rao, S. C. & Miller, E. K. Prospective coding for objects in primate prefrontal cortex. J. Neurosci. 19, 5493– 5505 (1999).
Squire, L. R. & Zola-Morgan, S. The medial temporal lobe memory system. Science 253, 1380– 1386 (1991).
Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M. & Tanila, H. The hippocampus, memory, and place cells: Is it spatial memory or a memory space? Neuron 23, 209 –226 (1999).
Ivry, R. B. The representation of temporal information in perception and motor control . Curr. Opin. Neurobiol. 6, 851– 857 (1996).
Graybiel, A. M. The basal ganglia and chunking of action sequences. Neurobiol. Learn. Mem. 70, 119–136 (1998).
Botvinick, M., Nystrom, L. E., Fissell, K., Carter, C. S. & Cohen, J. D. Conflict monitoring versus selection-for-action in anterior cingulate cortex. Nature 402, 179–181 (1999).
Fuster, J. M. Memory in the Cerebral Cortex (MIT Press, Cambridge, Massachusetts, 1995).
Petrides, M. Functional organization of the human frontal cortex for mnemonic processing — Evidence from neuroimaging studies. Ann. NY Acad. Sci. 769, 85–96 ( 1995).
Owen, A. M., Evans, A. C. & Petrides, M. Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: A positron emission tomography study. Cereb. Cortex 6, 31– 38 (1996).Evidence from human functional imaging that different prefrontal regions are involved in simple maintenance versus the monitoring and manipulation of information held ‘in mind’.
Petrides, M. Specialized systems for the processing of mnemonic information within the primate frontal cortex. Phil. Trans. R. Soc. Lond. B 351, 1455–1461 (1996).
Goldman-Rakic, P. S. in Vision and Movement Mechanisms in the Cerebral Cortex (eds Caminiti, R., Hoffman, K. P., Lacquaniti, F. & Altman, J.) 162– 172 (HFSP, Strasbourg, 1996).
Milner, B. Effects of different brain lesions on card sorting. Arch. Neurol. 9, 90 (1963).
Dias, R., Robbins, T. W. & Roberts, A. C. Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav. Neurosci. 110, 872–886 (1996).
Shallice, T. & Burgess, P. W. Deficits in strategy application following frontal lobe damage in man. Brain 114, 727–741 (1991).
Jones, E. G. & Powell, T. P. S. An anatomical study of converging sensory pathways within the cerebral cortex of the monkey. Brain 93, 793–820 ( 1970).
Chavis, D. A. & Pandya, D. N. Further observations on cortico–frontal connections in the rhesus monkey. Brain Res. 117, 369–386 (1976).
Acknowledgements
I thank Wael Asaad, Jonathan Cohen, Peter Dayan, John Duncan, Howard Eichenbaum, David Freedman, Tomaso Poggio, Maximilian Riesenhuber and Marlene Wicherski for valuable comments and discussions.
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Glossary
- TOP-DOWN
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Brain signals that convey knowledge derived from prior experience rather than sensory stimulation.
- GOAL-DIRECTED BEHAVIOUR
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Behaviour directed toward attainment of a future state (for example, obtaining a graduate degree).
- INTERNAL STATES
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Brain information not directly related to a sensory input or motor output; for example, homeostatic information such as hunger, thirst or other motivational influences.
- TASK CONTINGENCIES
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The logical structure of a given task (for example, if the light is green, cross the street).
- LIMBIC STRUCTURES
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A collection of subcortical structures important for processing memory and emotional information. Prominent structures include the hippocampus and amygdala.
- MULTIMODAL RESPONSES
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Neural activity elicited by more than one sensory modality.
- SACCADE
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A rapid, ballistic eye movement from one point of gaze to another.
- PREPOTENT RESPONSES
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Reflexive actions, either innate or well established through a great deal of experience.
- WORKING MEMORY
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The representation of items held in consciousness during experiences or after retrieval of memories. Short-lasting and associated with active rehearsal or manipulation of information.
- INFERIOR TEMPORAL CORTEX
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A neocortical region responsible for high-level analysis of form information.
- POSTERIOR PARIETAL CORTEX
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A region of the visual cortex thought to be involved in visuospatial, visuomotor and attentional processes.
- BASAL GANGLIA
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A collection of interconnected subcortical structures reciprocally connected to the prefrontal cortex.
- CEREBELLUM
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A structure overlying the pons that is important for sensorimotor coordination.
- ANTERIOR CINGULATE CORTEX
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A structure lying close to, and connected with, the prefrontal cortex, which is involved in error detection.
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Miller, E. The prefontral cortex and cognitive control. Nat Rev Neurosci 1, 59–65 (2000). https://doi.org/10.1038/35036228
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DOI: https://doi.org/10.1038/35036228
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