The prefrontal cortex (PFC) has been implicated in a variety of 'higher' cognitive functions — language, abstract reasoning, problem solving, social interactions and planning. A number of theories have been proposed for how the PFC might mediate these functions.
This paper proposes five criteria that we believe a theory should meet if it is to provide a useful framework for understanding the functions of the PFC. We provide an overview of some of the key PFC theories and assess how well they meet our criteria.
The criteria by which we assess the theories are: (1) specification of the type of information stored in the PFC; (2) consistency with our knowledge of stimulus representation in the brain; (3) consistency with what is known of the evolutionary development of the PFC; (4) ability to test the model and hence to verify or invalidate it; and (5) consistency of the model with available experimental data.
A theory might take a processing approach — that is, it might specify computational procedures that are performed by the PFC to manipulate information stored elsewhere in the brain. Alternatively, a theory can take a representational approach — that is, it can specify the type of information that is stored in memories in the PFC. Finally, a theory might have components of both the processing and representational viewpoints.
We discuss the main claims of each key theory and review data addressing these claims. The models meet our criteria to varying degrees. All models are supported to some extent by the available cognitive neuroscience data, but not all of the models address all of the available data. In particular, many researchers rely almost solely on functional neuroimaging data and ignore other sources of evidence (such as lesion studies). With respect to specific theories, without modification, no single theory of PFC function seems to explain all of the available data.
With respect to the general theoretical approaches, we argue that the representational approach seems to be more consistent with our criteria than does the processing approach. We argue that the representational approach forces a more detailed specification of a theory and thus enables specific hypothesis testing. We argue that adoption of a representational framework is the most parsimonious way to explore the nature of knowledge stored in the human PFC.
Through evolution, humans have acquired 'higher' cognitive skills — such as language, reasoning and planning — and complex social behaviour. Evidence from neuropsychological and neuroimaging research indicates that the prefrontal cortex (PFC) underlies much of this higher cognition. A number of theories have been proposed for how the PFC might achieve this. Although many of these theories focus on the types of 'process' that the PFC carries out, we argue for the validity of a representational approach to understanding PFC function.
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Semendeferi, K., Lu, A., Schenker, N. & Damasio, H. Humans and great apes share a large frontal cortex. Nature Neurosci. 5, 272–276 (2002).
Rilling, J. K. & Insel, T. R. The primate neocortex in comparative perspective using magnetic resonance imaging. J. Human Evol. 37, 191–223 (1999).
Semendeferi, K., Armstrong, E., Schleicher, A., Zilles, K. & van Hoesen, G. W. Prefrontal cortex in humans and apes: a comparative study of area 10. Am. J. Phys. Anthropol. 114, 224–241 (2001).
Levy, R. & Goldman-Rakic, P. S. Segregation of working memory functions within the dorsolateral prefrontal cortex. Exp. Brain Res. 133, 23–32 (2000).
Bodner, M., Kroger, J. & Fuster, J. M. Auditory memory cells in dorsolateral prefrontal cortex. Neuroreport 7, 1905–1908 (1996).
Fuster, J. M. & Alexander, G. E. Neuron activity related to short-term memory. Science 173, 652–654 (1971). A seminal paper demonstrating sustained activity in PFC neurons related to short-term memory of a stimulus over a delay period.
Fuster, J. M., Bodner, M. & Kroger, J. K. Cross-modal and cross-temporal association in neurons of frontal cortex. Nature 405, 347–351 (2000).
Elston, G. N. Pyramidal cells of the frontal lobe: all the more spinous to think with. J. Neurosci. 20, RC95 (2000).
Gallese, V., Fadiga, L., Fogassi, L. & Rizzolatti, G. Action recognition in the premotor cortex. Brain 119, 593–609 (1996).
Grafton, S. T., Arbib, M. A., Fadiga, L. & Rizzolatti, G. Localization of grasp representations in humans by PET: II. Observation compared with imagination. Exp. Brain Res. 112, 103–111 (1996).
Rizzolatti, G. et al. Localization of grasp representations in humans by PET: I. Observation versus execution. Exp. Brain Res. 111, 246–252 (1996).
Williams, J. H. G., Whiten, A., Suddendorf, T. & Perrett, D. I. Imitation, mirror neurons and autism. Neurosci. Biobehav. Rev. 25, 287–295 (2001). An interesting perspective on the PFC, action representation, imitation, and its relationship to social cognition and autism.
Banyas, C. A. in The Human Frontal Lobes: Functions and Disorders (eds Miller, B. L. & Cummings, J. L.) 83–106 (Guilford, New York, 1999).
Fuster, J. M. The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe (Raven, New York, 1997). A comprehensive review of research into PFC function and a detailed account of the temporal organization model.
Goldman-Rakic, P. S. in Handbook of Physiology: A Critical Comprehensive Presentation of Physiological Knowledge and Concepts (ed. Geiger, S. R.) 373–417 (American Physiological Society, Bethesda, Maryland, 1987).
Nichelli, P. et al. Where the brain appreciates the moral of a story. Neuroreport 6, 2309–2313 (1995).
Rueckert, L. & Grafman, J. Sustained attention deficits in patients with right frontal lesions. Neuropsychologia 34, 953–963 (1996).
Duncan, J. An adaptive coding model of neural function in prefrontal cortex. Nature Rev. Neurosci. 2, 820–829 (2001).
Freedman, D. J., Riesenhuber, M., Poggio, T. & Miller, E. K. Categorical representation of visual stimuli in the primate prefrontal cortex. Science 291, 312–316 (2001).
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).
Rao, S. C., Rainer, G. & Miller, E. K. Integration of what and where in the primate prefrontal cortex. Science 276, 821–824 (1997).
Cabeza, R. & Nyberg, L. Imaging cognition II: an empirical review of 275 PET and fMRI studies. J. Cogn. Neurosci. 12, 1–47 (2000). A comprehensive review of the functional imaging literature regarding most aspects of cognition.
Asaad, W. F., Rainer, G. & Miller, E. K. Task-specific neural activity in the primate prefrontal cortex. J. Neurophysiol. 84, 451–459 (2000).
Chang, J. Y., Chen, L., Luo, F., Shi, L. H. & Woodward, D. J. Neuronal responses in the frontal cortico-basal ganglia system during delayed matching-to-sample task: ensemble recording in freely moving rats. Exp. Brain Res. 142, 67–80 (2002).
Ramus, S. J. & Eichenbaum, H. Neural correlates of olfactory recognition memory in the rat orbitofrontal cortex. J. Neurosci. 20, 8199–8208 (2000).
Kawasaki, H. et al. Single-neuron responses to emotional visual stimuli recorded in the human ventral prefrontal cortex. Nature Neurosci. 4, 15–16 (2001).
Norman, D. A. & Shallice, T. in Consciousness and Self-regulation (eds Davidson, R. J., Schwartz, G. E. & Shapiro, D.) 1–18 (Plenum, New York, 1986).
Shallice, T. & Burgess, P. in The Prefrontal Cortex: Executive and Cognitive Functions (eds Roberts, A. C., Robbins, T. W. & Weiskrantz, L.) 22–35 (Oxford Univ. Press, Oxford, UK, 1998).
Dimitrov, M., Phipps, M., Zahn, T. & Grafman, J. A thoroughly modern Gage. Neurocase 5, 345–354 (1999).
Masterman, D. L. & Cummings, J. L. Frontal-subcortical circuits: the anatomic basis of executive, social and motivated behaviors. J. Psychopharmacol. 11, 107–114 (1997). This paper provides an excellent overview of the neural circuitry of the PFC and its relationship to behaviour.
Allain, P., Le Gall, D., Etcharry-Brouyx, F., Aubin, G. & Emile, J. Mental representation of knowledge following frontal-lobe lesion: dissociations on tasks using scripts. J. Clin. Exp. Neuropsychol. 21, 643–665 (1999).
Sirigu, A. et al. Encoding of sequence and boundaries of scripts following prefrontal lesions. Cortex 32, 297–310 (1996).
Crozier, S. et al. Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study. Neuropsychologia 37, 1469–1476 (1999).
Partiot, A., Grafman, J., Sadato, N., Flitman, S. & Wild, K. Brain activation during script event processing. Neuroreport 7, 761–766 (1996).
Wood, J. N., Romero, S. G., Makale, M. & Grafman, J. Category-specific representations of social and non-social knowledge in the human prefrontal cortex. J. Cogn. Neurosci. (in the press).
Koechlin, E., Corrado, G., Pietrini, P. & Grafman, J. Dissociating the role of the medial and lateral anterior prefrontal cortex in human planning. Proc. Natl Acad. Sci. USA 97, 7651–7656 (2000).
Braver, T. S., Barch, D. M., Gray, J. R., Molfese, D. L. & Snyder, A. Anterior cingulate cortex and response conflict: effects of frequency, inhibition and errors. Cereb. Cortex 11, 825–836 (2001).
MacDonald, A. W., Cohen, J. D., Stenger, V. A. & Carter, C. S. Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science 288, 1835–1838 (2000).
Menon, V., Adleman, N. E., White, C. D., Glover, G. H. & Reiss, A. L. Error-related brain activation during a Go/NoGo response inhibition task. Hum. Brain Mapp. 12, 131–143 (2001).
Buckner, R. L., Kelley, W. M. & Petersen, S. E. Frontal cortex contributes to human memory formation. Nature Neurosci. 2, 311–314 (1999).
Rugg, M. D. & Wilding, E. L. Retrieval processing and episodic memory. Trends Cogn. Sci. 4, 108–115 (2000).
Wagner, A. D., Desmond, J. E., Glover, G. H. & Gabrieli, J. D. Prefrontal cortex and recognition memory: functional-MRI evidence for context-dependent retrieval processes. Brain 121, 1985–2002 (1998).
Baker, S. C. et al. Neural systems engaged by planning: a PET study of the Tower of London task. Neuropsychologia 34, 515–526 (1996).
Strange, B. A., Henson, R. N. A., Friston, K. J. & Dolan, R. J. Anterior prefrontal cortex mediates rule learning in humans. Cereb. Cortex 11, 1040–1046 (2001).
Braver, T. S. & Bongiolatti, S. R. The role of frontopolar cortex in subgoal processing during working memory. Neuroimage 15, 523–536 (2002).
Burnod, Y. Organizational levels of the cerebral cortex: an integrated model. Acta Biotheor. 39, 351–361 (1991). An interesting approach to the functional integration of the cerebral cortex that does not focus simply on the PFC.
Guigon, E., Grandguillaume, P., Otto, I., Boutkhil, L. & Burnod, Y. Neural network models of cortical functions based on the computational properties of the cerebral cortex. J. Physiol. 88, 291–308 (1994). | PubMed |
Godbout, L. & Doyon, J. Mental representation of knowledge following frontal-lobe or postrolandic lesions. Neuropsychologia 33, 1671–1696 (1995).
Koechlin, E., Danek, A., Burnod, Y. & Grafman, J. Medial prefrontal and subcortical mechanisms underlying the acquisition of motor and cognitive action sequences. Neuron 35, 371–381 (2002).
Murray, E. A., Bussey, T. J. & Wise, S. P. Role of prefrontal cortex in a network for arbitrary visuomotor mapping. Exp. Brain Res. 133, 114–129 (2000).
Zalla, T., Plassiart, C., Pillon, B., Grafman, J. & Sirigu, A. Action planning in a virtual context after prefrontal cortex damage. Neuropsychologia 39, 759–770 (2001).
Zalla, T. et al. How patients with Parkinson's disease retrieve and manage cognitive event knowledge. Cortex 36, 163–179 (2000).
Grafman, J. in The Frontal Lobes (eds Stuss, D. T. H. & Knight, R. T.) 292–310 (Oxford Univ. Press, Oxford, UK, 2002). This book chapter provides a more detailed formulation of the SEC framework.
Grafman, J. et al. Frontal lobe injuries, violence, and aggression: a report of the Vietnam Head Injury Study. Neurology 46, 1231–1238 (1996).
Burgess, P. W., Veitch, E., de Lacy Costello, A. & Shallice, T. The cognitive and neuroanatomical correlates of multitasking. Neuropsychologia 38, 848–863 (2000).
Goel, V. & Grafman, J. Role of the right prefrontal cortex in ill-structured planning. Cogn. Neuropsychol. 17, 415–436 (2000).
Partiot, A., Grafman, J., Sadato, N., Wachs, J. & Hallett, M. Brain activation during the generation of non-emotional and emotional plans. Neuroreport 6, 1397–1400 (1995).
Gehring, W. J. & Knight, R. T. Prefrontal-cingulate interactions in action monitoring. Nature Neurosci. 3, 516–520 (2000).
Stone, V. E., Baron-Cohen, S. & Knight, R. T. Frontal contributions to theory of mind. J. Cogn. Neurosci. 10, 640–656 (1998).
Miller, E. K. & Cohen, J. D. An integrative theory of prefrontal cortex function. Annu. Rev. Neurosci. 24, 167–202 (2001). A useful summary of research into PFC functions that also presents a detailed account of the guided activation model.
Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. Willed action and the prefrontal cortex in man: a study with PET. Proc. R. Soc. Lond. B 244, 241–246 (1991).
Ó Scalaidhe, S. P., Wilson, F. A. & Goldman-Rakic, P. S. Areal segmentation of face-processing neurons in prefrontal cortex. Science 278, 1135–1138 (1997).
Wilson, F. A., Ó Scalaidhe, S. P. & Goldman-Rakic, P. S. Dissociation of object and spatial processing domains in primate prefrontal cortex. Science 260, 1955–1958 (1993).
Anderson, S. W., Bechara, A., Damasio, H., Tranel, D. & Damasio, A. R. Impairment of social and moral behavior related to early damage in human prefrontal cortex. Nature Neurosci. 2, 1032–1037 (1999).
Barrash, J., Tranel, D. & Anderson, S. W. Acquired personality distrubances associated with bilateral damage to the ventromedial prefrontal region. Dev. Neuropsychol. 18, 355–381 (2000).
Bechara, A., Damasio, H. & Damasio, A. R. Emotion, decision making and the orbitofrontal cortex. Cereb. Cortex 10, 295–307 (2000).
Rolls, E. T. The orbitofrontal cortex. Phil. Trans. R. Soc. Lond. B 351, 1433–1444 (1996).
Berthoz, S., Armony, J. L., Blair, R. J. & Dolan, R. J. An fMRI study of intentional and unintentional (embarrassing) violations of social norms. Brain 125, 1696–1708 (2002).
Moll, J., de Oliveira-Souza, R., Bramati, I. E. & Grafman, J. Functional networks in emotional moral and nonmoral social judgments. Neuroimage 16, 696–703 (2002).
Northoff, G. et al. Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study. Cereb. Cortex 10, 93–107 (2000).
Roberts, A. C. & Wallis, J. D. Inhibitory control and affective processing in the prefrontal cortex: neuropsychological studies in the common marmoset. Cereb. Cortex 10, 252–262 (2000).
Damasio, A. R. in Structure and Functions of the Human Prefrontal Cortex (eds Grafman, J., Holyoak, K. J. & Boller, F.) 241–251 (New York Academy of Sciences, New York, 1995).
Damasio, A. R. in The Prefrontal Cortex: Executive and Cognitive Functions (eds Roberts, A. C., Robbins, T. W. & Weiskrantz, L.) 36–50 (Oxford Univ. Press, Oxford, UK, 1998).
Bechara, A., Damasio, H., Tranel, D. & Damasio, A. R. Deciding advantageously before knowing the advantageous strategy. Science 275, 1293–1295 (1997).
Zahn, T. P., Grafman, J. & Tranel, D. Frontal lobe lesions and electrodermal activity: effects of significance. Neuropsychologia 37, 1227–1241 (1999).
Davidson, R. J. & Irwin, W. in Functional MRI (eds Moonen, C. T. W. & Bandettini, P. A.) 487–499 (Springer, New York, 2000).
Bechara, A., Tranel, D. & Damasio, H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain 123, 2189–2202 (2000).
Bechara, A., Tranel, D., Damasio, H. & Damasio, A. R. Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex. Cereb. Cortex 6, 215–225 (1996).
Kurata, K. Information processing for motor control in primate premotor cortex. Behav. Brain Res. 61, 135–142 (1994).
Toni, I., Thoenissen, D. & Zilles, K. Movement preparation and motor intention. Neuroimage 14, S110–117 (2001).
Harrington, D. L. et al. Specialized neural systems underlying representations of sequential movements. J. Cogn. Neurosci. 12, 56–77 (2000).
Averbeck, B. B., Chafee, M. V., Crowe, D. A. & Georgopoulos, A. P. Parallel processing of serial movements in prefrontal cortex. Proc. Natl Acad. Sci. USA 99, 13172–13177 (2002).
Paulus, M. P. et al. Prefrontal, parietal, and temporal cortex networks underlie decision-making in the presence of uncertainty. Neuroimage 13, 91–100 (2001).
Rubinsztein, J. S. et al. Decision-making in mania: a PET study. Brain 124, 2550–2563 (2001).
Elliott, R. & Dolan, R. J. Activation of different anterior cingulate foci in association with hypothesis testing and response selection. Neuroimage 8, 17–29 (1998).
Jentsch, J. D., Olausson, P., De La Garza, R. & Taylor, J. R. Impairments of reversal learning and response perseveration after repeated intermittent cocaine administrations to monkeys. Neuropsychopharmacology 26, 183–190 (2002).
Wallis, J. D., Dias, R., Robbins, T. W. & Roberts, A. C. Dissociable contributions of the orbitofrontal and lateral prefrontal cortex of the marmoset to performance on a detour reaching task. Eur. J. Neurosci. 13, 1797–1808 (2001).
Cummings, J. L. in Structure and Functions of the Human Prefrontal Cortex (eds Grafman, J., Holyoak, K. J. & Boller, F.) 1–13 (New York Academy of Sciences, New York, 1995).
Garavan, H., Ross, T. J. & Stein, E. A. Right hemispheric dominance of inhibitory control: an event-related fMRI study. Proc. Natl Acad. Sci. USA 96, 8301–8306 (1999).
Konishi, S. et al. Transient activation of inferior prefrontal cortex during cognitive set shifting. Nature Neurosci. 1, 80–84 (1998).
Konishi, S. et al. Common inhibitory mechanisms in the human inferior prefrontal cortex revealed by event-related functional MRI. Brain 22, 981–991 (1999).
Leung, H. C., Skudlarski, P., Gatenby, J. C., Peterson, B. S. & Gore, J. C. An event-related functional MRI study of the Stroop color word interference task. Cereb. Cortex 10, 552–560 (2000).
Casey, B. J. et al. Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging. Proc. Natl Acad. Sci. USA 97, 8728–8733 (2000).
Goldman-Rakic, P. S. in The Prefrontal Cortex: Executive and Cognitive Functions (eds Roberts, A. C., Robbins, T. W. & Weiskrantz, L.) 87–102 (Oxford Univ. Press, Oxford, UK, 1998).
Godefroy, O. & Rousseaux, M. Divided and focused attention in patients with lesion of the prefrontal cortex. Brain Cogn. 30, 155–174 (1996).
Koski, L. & Petrides, M. Distractibility after unilateral resections from the frontal and anterior cingulate cortex in humans. Neuropsychologia 40, 1059–1072 (2002).
Crofts, H. S. et al. Differential effects of 6-OHDA lesions of the frontal cortex and caudate nucleus on the ability to acquire an attentional set. Cereb. Cortex 11, 1015–1026 (2001).
Stuss, D. T. et al. Dissociation of attentional processes in patients with focal frontal and posterior lesions. Neuropsychologia 37, 1005–1027 (1999).
Klenberg, L., Korkman, M. & Lahti-Nuuttila, P. Differential development of attention and executive functions in 3- to 12-year-old Finnish children. Dev. Neuropsychol. 20, 407–428 (2001).
Bunge, S. A., Dudukovic, N. M., Thomason, M. E., Vaidya, C. J. & Gabrieli, J. D. E. Immature frontal lobe contributions to cognitive control in children: evidence from fMRI. Neuron 33, 301–311 (2002).
Helmstaedter, C., Gleibner, U., Zentner, J. & Elger, C. E. Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy. Neuropsychologia 36, 681–689 (1998).
Colvin, M. K., Dunbar, K. & Grafman, J. The effects of frontal lobe lesions on goal achievement in the water jug task. J. Cogn. Neurosci. 13, 1129–1147 (2001).
Goel, V. & Grafman, J. Are the frontal lobes implicated in 'planning' functions? Interpreting data from the Tower of Hanoi. Neuropsychologia 33, 623–642 (1995).
Goel, V., Grafman, J., Tajik, J., Gana, S. & Danto, D. A study of the performance of patients with frontal lobe lesions in a financial planning task. Brain 120, 1805–1822 (1997).
Burgess, P. W. & Shallice, T. Response suppression, initiation and strategy use following frontal lobe lesions. Neuropsychologia 34, 263–273 (1996).
Lee, S. S., Wild, K., Hollnagel, C. & Grafman, J. Selective visual attention in patients with frontal lobe lesions or Parkinson's disease. Neuropsychologia 37, 595–604 (1999).
Kaufer, D. I. & Lewis, D. A. in The Human Frontal Lobes: Functions and Disorders (eds Miller, B. L. & Cummings, J. L.) 27–44 (Guilford, New York, 1999).
- WORKING MEMORY
Activated long-term memory.
- SELECTIVE ATTENTION
Ability to focus mental effort on a subset of all available information.
- EPISODIC MEMORY
Memory for specific events that are temporally dated; includes the relationships between different events.
- SEMANTIC MEMORY
Memory for factual information about the world, concepts and word meaning.
Increased accessibility of information as a result of previous exposure to similar information.
- SOMATIC STATES
Emotional state as indicated by musculoskeletal and visceral (body) states.
- ASSOCIATIVE STRENGTH
The degree to which different representations are associated.
About this article
Cite this article
Wood, J., Grafman, J. Human prefrontal cortex: processing and representational perspectives. Nat Rev Neurosci 4, 139–147 (2003). https://doi.org/10.1038/nrn1033
Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up
British Journal of Nutrition (2020)
International Journal of Molecular Sciences (2020)
Social Neuroscience (2020)
Developmental Neuropsychology (2020)