The human orbitofrontal cortex: linking reward to hedonic experience

Holland, P. C. & Gallagher, M. Amygdala–frontal interactions and reward expectancy. Curr. Opin. Neurobiol. 14, 148–155 (2004). An excellent recent review of the converging evidence from mammals indicating that reinforcer expectancy is encoded through the interconnections between the basolateral complex of the amygdala and the orbitofrontal cortex.

Cardinal, R. N., Parkinson, J. A., Hall, J. & Everitt, B. J. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci. Biobehav. Rev. 26, 321–352 (2002).

O'Doherty, J. et al. Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex. Neuroreport 11, 893–897 (2000).

Gottfried, J. A., O'Doherty, J. & Dolan, R. J. Encoding predictive reward value in human amygdala and orbitofrontal cortex. Science 301, 1104–1107 (2003). A demonstration of how predictive reward value is encoded in the human brain in the orbitofrontal cortex and amygdala.

Kringelbach, M. L., O'Doherty, J., Rolls, E. T. & Andrews, C. Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb. Cortex 13, 1064–1071 (2003). A clear demonstration that neural activity in the orbitofrontal cortex is correlated with hedonic experience.

Fuster, J. M. The Prefrontal Cortex (Raven, New York, USA, 1997).

Pandya, D. N. & Yeterian, E. H. Comparison of prefrontal architecture and connections. Phil. Trans. R. Soc. Lond. B 351, 1423–1432 (1996).

Brodmann, K. Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues (Barth, Leipzig, Germany, 1909).

Walker, A. E. A cytoarchitectural study of the prefrontal area of the macaque monkey. J. Comp. Neurol. 73, 59–86 (1940).

Petrides, M. & Pandya, D. N. in Handbook of Neuropsychology Vol. 9 (eds Boller, F. & Grafman, J.) 17–58 (Elsevier, Amsterdam, 1994).

Carmichael, S. T. & Price, J. L. Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey. J. Comp. Neurol. 346, 366–402 (1994).

Chiavaras, M. M. & Petrides, M. Orbitofrontal sulci of the human and macaque monkey brain. J. Comp. Neurol. 422, 35–54 (2000).

Chiavaras, M. M. & Petrides, M. Three-dimensional probabilistic atlas of the human orbitofrontal sulci in standardized stereotaxic space. Neuroimage 13, 479–496 (2001).

Carmichael, S. T. & Price, J. L. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 363, 642–664 (1995).

Barbas, H. Anatomic organization of basoventral and mediodorsal visual recipient prefrontal regions in the rhesus monkey. J. Comp. Neurol. 276, 313–342 (1988).

Amaral, D. G. & Price, J. L. Amygdalo-cortical projections in the monkey (Macaca fascicularis). J. Comp. Neurol. 230, 465–496 (1984).

Carmichael, S. T. & Price, J. L. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. J. Comp. Neurol. 363, 615–641 (1995).

Van Hoesen, G. W., Morecraft, R. J. & Vogt, B. A. in The Neurobiology of the Cingulate Cortex and Limbic Thalamus: A Comprehensive Handbook (eds Vogt, B. A. & Gabriel, M.) 249–284 (Birkhäuser, Boston, USA, 1993).

Öngür, D. & Price, J. L. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex 10, 206–219 (2000).

Mesulam, M. -M. & Mufson, E. J. Insula of the old world monkey. III Efferent cortical output and comments on function. J. Comp. Neurol. 212, 38–52 (1982).

Rempel-Clower, N. L. & Barbas, H. Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey. J. Comp. Neurol. 398, 393–419 (1998).

Cavada, C., Company, T., Tejedor, J., Cruz Rizzolo, R. J. & Reinoso Suarez, F. The anatomical connections of the macaque monkey orbitofrontal cortex. A review. Cereb. Cortex 10, 220–242 (2000).

Eblen, F. & Graybiel, A. M. Highly restricted origin of prefrontal cortical inputs to striosomes in the macaque monkey. J. Neurosci. 15, 5999–6013 (1995).

Barbas, H. & Pandya, D. N. Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey. J. Comp. Neurol. 286, 353–375 (1989).

Nauta, W. J. The problem of the frontal lobe: a reinterpretation. J. Psychiatr. Res. 8, 167–187 (1971).

Rolls, E. T. The Brain and Emotion (Oxford Univ. Press, Oxford, 1999).

Bechara, A., Damasio, A. R., Damasio, H. & Anderson, S. W. Insensitivity to future consequences following damage to human prefrontal cortex. Cognition 50, 7–15 (1994). A classic paper showing that patients with lesions to the orbitofrontal and medial prefrontal cortices are impaired at real-life decision making, although they retain otherwise normal intellectual functions.

Kringelbach, M. L. & Rolls, E. T. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog. Neurobiol. 72, 341–372 (2004). A review of the functions of the human orbitofrontal cortex, including a large meta-analysis of neuroimaging studies showing that different subregions of the orbitofrontal cortex have different functions.

Elliott, R., Dolan, R. J. & Frith, C. D. Dissociable functions in the medial and lateral orbitofrontal cortex: evidence from human neuroimaging studies. Cereb. Cortex 10, 308–317 (2000).

Dias, R., Robbins, T. & Roberts, A. Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380, 69–72 (1996).

Rolls, E. T., Hornak, J., Wade, D. & McGrath, J. Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. J. Neurol. Neurosurg. Psychiatry 57, 1518–1524 (1994).

Iversen, S. D. & Mishkin, M. Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity. Exp. Brain Res. 11, 376–386 (1970). A classic lesioning study that showed the importance of the lateral orbitofrontal cortex in reversal learning in monkeys.

Hornak, J. et al. Reward-related reversal learning after surgical excisions in orbitofrontal and dorsolateral prefrontal cortex in humans. J. Cogn. Neurosci. 16, 463–478 (2004).

Damasio, A. R. The somatic marker hypothesis and the possible functions of the prefrontal cortex. Phil. Trans. R. Soc. Lond. B 351, 1413–1420 (1996).

James, W. The Principles of Psychology (Henry Holt, New York, USA, 1890).

Lange, C. G. Über Gemüstbewegungen. (Org. Om Sindsbevægelser) (Theodor Thomas, Leipzig, Germany, 1887).

Cannon, W. B. The James–Lange theory of emotion. Am. J. Psychol. 39, 106–124 (1927).

Craig, A. D. How do you feel? Interoception: the sense of the physiological condition of the body. Nature Rev. Neurosci. 3, 655–666 (2002).

Wilson, J. et al. Fast, fully automated global and local magnetic field optimization for fMRI of the human brain. Neuroimage 17, 967–976 (2002).

Deichmann, R., Josephs, O., Hutton, C., Corfield, D. R. & Turner, R. Compensation of susceptibility-induced BOLD sensitivity losses in echo-planar fMRI imaging. Neuroimage 15, 120–135 (2002).

Frey, S., Kostopoulos, P. & Petrides, M. Orbitofrontal involvement in the processing of unpleasant auditory information. Eur. J. Neurosci. 12, 3709–3712 (2000).

Small, D. M. et al. Human cortical gustatory areas: a review of functional neuroimaging data. Neuroreport 10, 7–14 (1999).

Zatorre, R. J., Jones-Gotman, M., Evans, A. C. & Meyer, E. Functional localization and lateralization of human olfactory cortex. Nature 360, 339–340 (1992).

Rolls, E. T. et al. Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices. Cereb. Cortex 13, 308–317 (2003).

Aharon, I. et al. Beautiful faces have variable reward value: fMRI and behavioral evidence. Neuron 32, 537–551 (2001).

Critchley, H. D., Mathias, C. J. & Dolan, R. J. Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy. Neuron 33, 653–663 (2002).

Thut, G. et al. Activation of the human brain by monetary reward. Neuroreport 8, 1225–1228 (1997).

O'Doherty, J., Kringelbach, M. L., Rolls, E. T., Hornak, J. & Andrews, C. Abstract reward and punishment representations in the human orbitofrontal cortex. Nature Neurosci. 4, 95–102 (2001).

Small, D. M., Jones-Gotman, M., Zatorre, R. J., Petrides, M. & Evans, A. C. Flavor processing: more than the sum of its parts. Neuroreport 8, 3913–3917 (1997).

De Araujo, I. E. T., Rolls, E. T., Kringelbach, M. L., McGlone, F. & Phillips, N. Taste–olfactory convergence, and the representation of the pleasantness of flavour, in the human brain. Eur. J. Neurosci. 18, 2059–2068 (2003).

Rolls, B. J., Rolls, E. T., Rowe, E. A. & Sweeney, K. Sensory specific satiety in man. Physiol. Behav. 27, 137–142 (1981).

Butter, C. M., Mishkin, M. & Rosvold, H. E. Conditioning and extinction of a food-rewarded response after selective ablations of frontal cortex in rhesus monkeys. Exp. Neurol. 7, 65–75 (1963).

Baylis, L. L. & Gaffan, D. Amygdalectomy and ventromedial prefrontal ablation produce similar deficits in food choice and in simple object discrimination learning for an unseen reward. Exp. Brain Res. 86, 617–622 (1991).

Baxter, M. G., Parker, A., Lindner, C. C., Izquierdo, A. D. & Murray, E. A. Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex. J. Neurosci. 20, 4311–4319 (2000).

Rahman, S., Sahakian, B. J., Hodges, J. R., Rogers, R. D. & Robbins, T. W. Specific cognitive deficits in mild frontal variant frontotemporal dementia. Brain 122, 1469–1493 (1999).

Farrow, T. F. et al. Investigating the functional anatomy of empathy and forgiveness. Neuroreport 12, 2433–2438 (2001).

Blood, A. J., Zatorre, R. J., Bermudez, P. & Evans, A. C. Emotional responses to pleasant and unpleasant music correlate with activity in paralimbic brain regions. Nature Neurosci. 2, 382–387 (1999).

Rozin, P. in International Encyclopedia of the Social & Behavioral Sciences (eds Smelser, N. J. & Baltes, P. B.) 5719–5722 (Elsevier, Amsterdam, 2001).

Harlow, J. M. Passage of an iron rod through the head. Boston Med. Surg. J. 39, 389–393 (1848).

Macmillan, M. An Odd Kind of Fame: Stories of Phineas Gage (MIT Press, Cambridge, Massachusetts, 2000).

Blair, R. J. & Cipolotti, L. Impaired social response reversal. A case of 'acquired sociopathy'. Brain 123, 1122–1141 (2000).

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).

Hornak, J. et al. Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices. Brain 126, 1671–1712 (2003). Strong evidence from surgically circumscribed lesions in humans showing that the orbitofrontal and medial prefrontal cortices are involved in emotion identification, social behaviour and subjective emotional state.

Hornak, J., Rolls, E. T. & Wade, D. Face and voice expression identification in patients with emotional and behavioural changes following ventral frontal lobe damage. Neuropsychologia 34, 247–261 (1996).

Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473–500 (2000).

Bechara, A., Damasio, H., Tranel, D. & Anderson, S. W. Dissociation of working memory from decision making within the human prefrontal cortex. J. Neurosci. 18, 428–437 (1998).

Maia, T. V. & McLelland, J. L. A reexamination of the evidence for the somatic marker hypothesis: what participants really know in the Iowa gambling task. Proc. Natl Acad. Sci. USA 101, 16075–16080 (2004).

Rogers, R. D. et al. Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex. J. Neurosci. 19, 9029–9038 (1999).

Rolls, E. T., Kringelbach, M. L. & de Araujo, I. E. T. Different representations of pleasant and unpleasant odors in the human brain. Eur. J. Neurosci. 18, 695–703 (2003).

Anderson, A. K. et al. Dissociated neural representations of intensity and valence in human olfaction. Nature Neurosci. 6, 196–202 (2003).

Small, D. M. et al. Dissociation of neural representation of intensity and affective valuation in human gustation. Neuron 39, 701–711 (2003).

Schnider, A. & Ptak, R. Spontaneous confabulators fail to suppress currently irrelevant memory traces. Nature Neurosci. 2, 677–681 (1999).

Schnider, A. Spontaneous confabulation and the adaptation of thought to ongoing reality. Nature Rev. Neurosci. 4, 662–671 (2003). A fascinating review article that links the medial orbitofrontal cortex to spontaneous confabulation in patients and proposes that this region might serve to adapt to ongoing reality.

Schnider, A., Treyer, V. & Buck, A. The human orbitofrontal cortex monitors outcomes even when no reward is at stake. Neuropsychologia 43, 316–323 (2005).

Petrovic, P., Kalso, E., Petersson, K. M. & Ingvar, M. Placebo and opioid analgesia — imaging a shared neuronal network. Science 295, 1737–1740 (2002). An elegant demonstration of placebo mechanisms in the human brain in which the pain relief in placebo-responders is correlated with activity in lateral orbitofrontal and anterior cingulate cortices.

Petrovic, P. & Ingvar, M. Imaging cognitive modulation of pain processing. Pain 95, 1–5 (2002).

Nobre, A. C., Coull, J. T., Frith, C. D. & Mesulam, M. M. Orbitofrontal cortex is activated during breaches of expectation in tasks of visual attention. Nature Neurosci. 2, 11–12 (1999).

Kringelbach, M. L. & Rolls, E. T. Neural correlates of rapid context-dependent reversal learning in a simple model of human social interaction. Neuroimage 20, 1371–1383 (2003).

Kringelbach, M. L. Learning to change. PLoS Biol. 2, E140 (2004).

Blair, R. J., Morris, J. S., Frith, C. D., Perrett, D. I. & Dolan, R. J. Dissociable neural responses to facial expressions of sadness and anger. Brain 122, 883–893 (1999).

Walton, M. E., Devlin, J. T. & Rushworth, M. F. Interactions between decision making and performance monitoring within prefrontal cortex. Nature Neurosci. 7, 1259–1265 (2004). An important paper that demonstrates the central role played by the orbitofrontal and anterior cingulate cortices in decision making.

Ullsperger, M. & von Cramon, D. Y. Decision making, performance and outcome monitoring in frontal cortical areas. Nature Neurosci. 7, 1173–1174 (2004).

Chalmers, D. Facing up to the problem of consciousness. J. Conscious. Stud. 2, 200–219 (1995).

Hull, C. L. Essentials of Behavior (Yale Univ. Press, New Haven, Connecticut, USA, 1951).

Bindra, D. How adaptive behavior is produced: a perceptual–motivational alternative to response-reinforcement. Behav. Brain Sci. 1, 41–91 (1978).

Cabanac, M. Physiological role of pleasure. Science 173, 1103–1107 (1971).

Berridge, K. C. Food reward: brain substrates of wanting and liking. Neurosci. Biobehav. Rev. 20, 1–25 (1996).

Berridge, K. C. & Robinson, T. E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res. Brain Res. Rev. 28, 309–369 (1998).

Kringelbach, M. L. Food for thought: hedonic experience beyond homeostasis in the human brain. Neuroscience 126, 807–819 (2004).

Saper, C. B., Chou, T. C. & Elmquist, J. K. The need to feed: homeostatic and hedonic control of eating. Neuron 36, 199–211 (2002).

Kringelbach, M. L., O'Doherty, J., Rolls, E. T. & Andrews, C. Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb. Cortex 13, 1064–1071 (2003).

Hinton, E. C. et al. Neural contributions to the motivational control of appetite in humans. Eur. J. Neurosci. 20, 1411–1418 (2004). Demonstrates that the extrinsic incentive value of foods is located in mid-anterior parts of the orbitofrontal cortex.

De Araujo, I. E. T., Kringelbach, M. L., Rolls, E. T. & Hobden, P. The representation of umami taste in the human brain. J. Neurophysiol. 90, 313–319 (2003). Shows that the subjective synergistic enhancement of umami taste is represented in mid-anterior parts of the orbitofrontal cortex.

De Araujo, I. E. T., Kringelbach, M. L., Rolls, E. T. & McGlone, F. Human cortical responses to water in the mouth, and the effects of thirst. J. Neurophysiol. 90, 1865–1876 (2003).

Small, D. M., Zatorre, R. J., Dagher, A., Evans, A. C. & Jones-Gotman, M. Changes in brain activity related to eating chocolate: from pleasure to aversion. Brain 124, 1720–1733 (2001).

De Araujo, I. E. & Rolls, E. T. Representation in the human brain of food texture and oral fat. J. Neurosci. 24, 3086–3093 (2004).

Craig, A. D., Chen, K., Bandy, D. & Reiman, E. M. Thermosensory activation of insular cortex. Nature Neurosci. 3, 184–190 (2000).

Völlm, B. A. et al. Methamphetamine activates reward circuitry in drug naïve human subjects. Neuropsychopharmacology 29, 1715–1722 (2004).

Blood, A. J. & Zatorre, R. J. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc. Natl Acad. Sci. USA 98, 11818–11823 (2001).

Hornak, J. et al. Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices. Brain 126, 1671–1712 (2003).

Drevets, W. C. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr. Opin. Neurobiol. 11, 240–249 (2001).

Volkow, N. D. & Li, T. K. Drug addiction: the neurobiology of behaviour gone awry. Nature Rev. Neurosci. 5, 963–970 (2004).

Dehaene, S., Kerszberg, M. & Changeux, J. P. A neuronal model of a global workspace in effortful cognitive tasks. Proc. Natl Acad. Sci. USA 95, 14529–14534 (1998).

Gusnard, D. A. & Raichle, M. E. Searching for a baseline: functional imaging and the resting human brain. Nature Rev. Neurosci. 2, 685–694 (2001).

Granger, C. W. J. Investigating causal relations by econometric models and cross-spectral methods. Econometrica 37, 424–438 (1969).

Dehaene, S. et al. Cerebral mechanisms of word masking and unconscious repetition priming. Nature Neurosci. 4, 752–758 (2001).

Eslinger, P. J., Flaherty-Craig, C. V. & Benton, A. L. Developmental outcomes after early prefrontal cortex damage. Brain Cogn. 55, 84–103 (2004).

Uylings, H. B. & van Eden, C. G. Qualitative and quantitative comparison of the prefrontal cortex in rat and in primates, including humans. Prog. Brain Res. 85, 31–62 (1990).

Öngür, D. & Price, J. L. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex 10, 206–219 (2000). An important paper proposing that, on neuroanatomical grounds, the orbitofrontal cortex should be considered along with the medial prefrontal cortex as a crucial sensory–visceromotor link for consummatory behaviours.

Papez, J. Comparative Neurology (Crowell, New York, 1929).

Brodmann, K. Neue Ergebnisse ueber die Vergleichende histologische Localisation der Grosshirnfinde mit besonderer Berucksichtigung des Stirnhirns. Anat. Anz. Suppl. 41, 157–216 (1912).

Passingham, R. E. The Human Primate (W. H. Freeman, Oxford, 1982).

Schoenbaum, G. & Setlow, B. Integrating orbitofrontal cortex into prefrontal theory: common processing themes across species and subdivisions. Learn. Mem. 8, 134–147 (2001).

Darwin, C. The Expression of the Emotions in Man and Animals (Univ. Chicago Press, Chicago, 1872).

Kringelbach, M. L. in The Oxford Companion to the Mind 2nd edn (ed. Gregory, R. L.) 287–290 (Oxford Univ. Press, Oxford, 2004).

Weiskrantz, L. in Analysis of Behavioural Change (ed. Weiskrantz, L.) 50–90 (Harper and Row, New York/London, 1968).

Gogtay, N. et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc. Natl Acad. Sci. USA 101, 8174–8179 (2004).