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What the orbitofrontal cortex does not do

Abstract

The number of papers about the orbitofrontal cortex (OFC) has grown from 1 per month in 1987 to a current rate of over 50 per month. This publication stream has implicated the OFC in nearly every function known to cognitive neuroscience and in most neuropsychiatric diseases. However, new ideas about OFC function are typically based on limited data sets and often ignore or minimize competing ideas or contradictory findings. Yet true progress in our understanding of an area's function comes as much from invalidating existing ideas as proposing new ones. Here we consider the proposed roles for OFC, critically examining the level of support for these claims and highlighting the data that call them into question.

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Figure 1: The (lateral) OFC across species.
Figure 2: Taxonomy of proposed OFC functions.

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References

  1. Popper, K. The Logic of Scientific Discovery (Hutchinson & Co, 1959).

  2. Noonan, M.P., Kolling, N., Walton, M.E. & Rushworth, M.F. Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement. Eur. J. Neurosci. 35, 997–1010 (2012).

    Article  CAS  PubMed  Google Scholar 

  3. Wallis, J.D. Cross-species studies of orbitofrontal cortex and value-based decision-making. Nat. Neurosci. 15, 13–19 (2012).

    Article  CAS  Google Scholar 

  4. Rudebeck, P.H. & Murray, E.A. Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values. Ann. NY Acad. Sci. 1239, 1–13 (2011).

    Article  PubMed  Google Scholar 

  5. Ferrier, D. The Functions of the Brain (GP Putnam's Sons, New York, 1876).

  6. Harlow, J.M. Recovery after passage of an iron bar through the head. Pub. Mass. Med. Soc. 2, 329–346 (1868).

    Google Scholar 

  7. Jones, B. & Mishkin, M. Limbic lesions and the problem of stimulus-reinforcement associations. Exp. Neurol. 36, 362–377 (1972).

    Article  CAS  PubMed  Google Scholar 

  8. Walton, M.E., Behrens, T.E.J., Buckley, M.J., Rudebeck, P.H. & Rushworth, M.F.S. Separable learning systems in teh macaque brain and the role of the orbitofrontal cortex in contingent learning. Neuron 65, 927–939 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Meunier, M., Bachevalier, J. & Mishkin, M. Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys. Neuropsychologia 35, 999–1015 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Bechara, A., Damasio, H., Tranel, D. & Damasio, A.R. Deciding advantageously before knowing the advantageous strategy. Science 275, 1293–1295 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Izquierdo, A., Suda, R.K. & Murray, E.A. Bilateral orbital prefrontal cortex lesions in rhesus monkeys disrupt choices guided by both reward value and reward contingency. J. Neurosci. 24, 7540–7548 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chudasama, Y. & Robbins, T.W. Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex. J. Neurosci. 23, 8771–8780 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Kim, J. & Ragozzino, K.E. The involvement of the orbitofrontal cortex in learning under changing task contingencies. Neurobiol. Learn. Mem. 83, 125–133 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fellows, L.K. & Farah, M.J. Ventromedial frontal cortex mediates affective shifting in humans: evidence from a reversal learning paradigm. Brain 126, 1830–1837 (2003).

    Article  PubMed  Google Scholar 

  17. Tsuchida, A., Doll, B.B. & Fellows, L.K. Beyond reversal: a critical role for human orbitofrontal cortex in flexible learning from probabilistic feedback. J. Neurosci. 30, 16868–16875 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Riceberg, J.S. & Shapiro, M.L. Reward stability determines the contribution of orbitofrontal cortex to adaptive behavior. J. Neurosci. 32, 16402–16409 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Izquierdo, A. & Jentsch, J.D. Reversal learning as a measure of impulsive and compulsive behavior in addictions. Psychopharmacology (Berl.) 219, 607–620 (2012).

    Article  CAS  Google Scholar 

  20. 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).

    Article  PubMed  Google Scholar 

  21. Schoenbaum, G., Nugent, S., Saddoris, M.P. & Setlow, B. Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations. Neuroreport 13, 885–890 (2002).

    Article  PubMed  Google Scholar 

  22. Schoenbaum, G., Setlow, B., Nugent, S.L., Saddoris, M.P. & Gallagher, M. Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals. Learn. Mem. 10, 129–140 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kazama, A. & Bachevalier, J. Selective aspiration or neurotoxic lesions of orbital frontal areas 11 and 13 spared monkeys′ performance on the object discrimination reversal task. J. Neurosci. 29, 2794–2804 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rudebeck, P.H., Saunders, R.C., Prescott, A.T., Chau, L.S. & Murray, E.A. Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating. Nat. Neurosci. 16, 1140–1145 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rudebeck, P.H. & Murray, E.A. Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning. J. Neurosci. 28, 8338–8343 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Winstanley, C.A., Theobald, D.E.H., Cardinal, R.N. & Robbins, T.W. Contrasting roles of basolateral amygdala and orbitofrontal cortex in impulsive choice. J. Neurosci. 24, 4718–4722 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chudasama, Y., Kralik, J.D. & Murray, E.A. Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task. Cereb. Cortex 17, 1154–1159 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Wallis, J.D. Orbitofrontal cortex and its contribution to decision-making. Annu. Rev. Neurosci. 30, 31–56 (2007).

    Article  CAS  PubMed  Google Scholar 

  29. Aron, A.R., Robbins, T.W. & Poldrack, R.A. Inibition and the right inferior frontal cortex: one decade on. Trends Cogn. Sci. 18, 177–185 (2014).

    Article  PubMed  Google Scholar 

  30. Rolls, E.T. The orbitofrontal cortex. Phil. Trans. R. Soc. Lond. B 351, 1433–1443 (1996).

    Article  CAS  Google Scholar 

  31. Thorpe, S.J., Rolls, E.T. & Maddison, S. The orbitofrontal cortex: neuronal activity in the behaving monkey. Exp. Brain Res. 49, 93–115 (1983).

    Article  CAS  PubMed  Google Scholar 

  32. Critchley, H.D. & Rolls, E.T. Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. J. Neurophysiol. 75, 1673–1686 (1996).

    Article  CAS  PubMed  Google Scholar 

  33. Critchley, H.D. & Rolls, E.T. Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task. J. Neurophysiol. 75, 1659–1672 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Rolls, E.T., Critchley, H.D., Mason, R. & Wakeman, E.A. Orbitofrontal cortex neurons: role in olfactory and visual association learning. J. Neurophysiol. 75, 1970–1981 (1996).

    Article  CAS  PubMed  Google Scholar 

  35. Cohen, J.Y., Haesler, S., Vong, L., Lowell, B.B. & Uchida, N. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature (in the press) (2012).

  36. Burke, K.A., Takahashi, Y.K., Correll, J., Brown, P.L. & Schoenbaum, G. Orbitofrontal inactivation impairs reversal of Pavlovian learning by interfering with ‘disinhibition’ of responding for previously unrewarded cues. Eur. J. Neurosci. 30, 1941–1946 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Takahashi, Y.K. et al. The orbitofrontal cortex and ventral tegmental area are necessary for learning from unexpected outcomes. Neuron 62, 269–280 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gallagher, M., McMahan, R.W. & Schoenbaum, G. Orbitofrontal cortex and representation of incentive value in associative learning. J. Neurosci. 19, 6610–6614 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. McAlonan, K. & Brown, V.J. Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behav. Brain Res. 146, 97–103 (2003).

    Article  PubMed  Google Scholar 

  41. Bissonette, G.B. et al. Double dissociation of the effects of medial and orbital prefrontal cortical lesions on attentional and affective shifts in mice. J. Neurosci. 28, 11124–11130 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ostlund, S.B. & Balleine, B.W. Orbitofrontal cortex mediates outcome encoding in Pavlovian but not instrumental learning. J. Neurosci. 27, 4819–4825 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Izquierdo, A.D. & Murray, E.A. Bilateral orbital prefrontal cortex lesions disrupt reinforcer devaluation effects in rhesus monkeys. Soc. Neurosci. Abstr. 26, 978 (2000).

    Google Scholar 

  44. West, E.A., Forcelli, P.A., McCue, D.L. & Malkova, L. Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats. Behav. Brain Res. 246, 10–14 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Schoenbaum, G., Chiba, A.A. & Gallagher, M. Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning. J. Neurosci. 19, 1876–1884 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Paton, J.J., Belova, M.A., Morrison, S.E. & Salzman, C.D. The primate amygdala represents the positive and negative value of visual stimuli during learning. Nature 439, 865–870 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Morrison, S.E., Saez, A., Lau, B. & Salzman, C.D. Different time courses for learning-related changes in amygdala and orbitofrontal cortex. Neuron 71, 1127–1140 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kennerley, S.W., Dahmubed, A.F., Lara, A.H. & Wallis, J.D. Neurons in the frontal lobe encode the value of multiple decision variables. J. Cogn. Neurosci. 21, 1162–1178 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kennerley, S.W. & Wallis, J.D. Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables. Eur. J. Neurosci. 29, 2061–2073 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kennerley, S.W., Behrens, T.E. & Wallis, J.D. Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. Nat. Neurosci. 14, 181–1589 (2011).

    Article  CAS  Google Scholar 

  51. Stalnaker, T.A., Roesch, M.R., Franz, T.M., Burke, K.A. & Schoenbaum, G. Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-making. Eur. J. Neurosci. 24, 2643–2653 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Rescorla, R.A. Pavlovian conditioning: it's not what you think it is. Am. Psychol. 43, 151–160 (1988).

    Article  CAS  PubMed  Google Scholar 

  53. Lang, P.J. The varieties of emotional experience: a meditation on James-Lange theory. Psychol. Rev. 101, 211–221 (1994).

    Article  CAS  PubMed  Google Scholar 

  54. Maia, T.V. & McClelland, 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bechara, A., Damasio, H., Damasio, A.R. & Lee, G.P. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. J. Neurosci. 19, 5473–5481 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bechara, A., Tranel, D. & Damasio, H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain 123, 2189–2202 (2000).

    Article  PubMed  Google Scholar 

  57. Bechara, A. Neurobiology of decision-making: risk and reward. Semin. Clin. Neuropsychiatry 6, 205–216 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Bechara, A. et al. Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia 39, 376–389 (2001).

    Article  CAS  PubMed  Google Scholar 

  59. Bechara, A. & Damasio, H. Decision-making and addiction (part I): impaired activation of somatic states in substance dependent individuals when pondering decisions with negative future consequences. Neuropsychologia 40, 1675–1689 (2002).

    Article  PubMed  Google Scholar 

  60. Pais-Vieira, M., Lima, D. & Galhardo, V. Orbitofrontal cortex lesions disrupt risk assessment in a novel serial decision-making task for rats. Neuroscience 145, 225–231 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Zeeb, F.D. & Winstanley, C.A. Lesions of the basolateral amygdala and the orbitofrontal cortex differentially affect acquisition and performance of a rodent gambling task. J. Neurosci. 31, 2197–2204 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zeeb, F.D. & Winstanley, C.A. Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals′ ability to alter decision-making behavior after reinforcer devaluation. J. Neurosci. 33, 6434–6443 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fellows, L.K. & Farah, M.J. Different underlying impairments in decision-making following ventromedial and dorsolateral frontal lobe damage in humans. Cereb. Cortex 15, 58–63 (2005).

    Article  PubMed  Google Scholar 

  64. Fellows, L.K. The role of orbitofrontal cortex in decision making: a component process account. Ann. NY Acad. Sci. 1121, 421–430 (2007).

    Article  PubMed  Google Scholar 

  65. Daw, N.D., Niv, Y. & Dayan, P. Uncertainty-based competition between prefrontal and dorsolateral striatal systems for behavioral control. Nat. Neurosci. 8, 1704–1711 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Dayan, P., Niv, Y., Seymour, P. & Daw, N.D. The misbehavior of value and the discipline of the will. Neural Netw. 19, 1153–1160 (2006).

    Article  PubMed  Google Scholar 

  67. Huys, Q.J. et al. Bonsai trees in your head: how the Pavlovian system sculpts goal-directed choices by pruning decision trees. PLoS Comput. Biol. 8, e1002410 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. McDannald, M.A. et al. Model-based learning and the contribution of the orbitofrontal cortex to the model-free world. Eur. J. Neurosci. 35, 991–996 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Bechara, A., Dolan, S. & Hindes, A. Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward? Neuropsychologia 40, 1690–1705 (2002).

    Article  PubMed  Google Scholar 

  70. O'Doherty, J.P. The problem with value. Neurosci. Biobehav. Rev. 43, 259–268 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Pearson, J.M., Watson, K.K. & Platt, M.L. Decision making: the neuroethological turn. Neuron 82, 950–965 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Montague, P.R. & Berns, G.S. Neural economics and the biological substrates of valuation. Neuron 36, 265–284 (2002).

    Article  CAS  PubMed  Google Scholar 

  73. Padoa-Schioppa, C. Neurobiology of economic choice: a goods-based model. Annu. Rev. Neurosci. 34, 333–359 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Levy, D.J. & Glimcher, P.W. The root of all value: a neural common currency for choice. Curr. Opin. Neurobiol. 22, 1027–1038 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Padoa-Schioppa, C. & Assad, J.A. Neurons in orbitofrontal cortex encode economic value. Nature 441, 223–226 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Padoa-Schioppa, C. & Assad, J.A. The representation of economic value in the orbitofrontal cortex is invariant for changes in menu. Nat. Neurosci. 11, 95–102 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Padoa-Schioppa, C. Range-adapting representation of economic value in the orbitofrontal cortex. J. Neurosci. 29, 14004–14014 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Plassmann, H., O'Doherty, J. & Rangel, A. Orbitofrontal cortex encodes willingness to pay in everyday economic transactions. J. Neurosci. 27, 9984–9988 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. McNamee, D., Rangel, A. & O'Doherty, J.P. Category-dependent and category-independent goal-value codes in human ventromedial prefrontal cortex. Nat. Neurosci. 16, 479–485 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Levy, D.J. & Glimcher, P.W. Comparing apples and oranges: using reward-specific and reward-general subjective value representation in the brain. J. Neurosci. 31, 14693–14707 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lebreton, M., Jorge, S., Michel, V., Thirion, B. & Pessiglione, M. An automatic valuation system in the human brain: evidence from functional neuroimaging. Neuron 64, 431–439 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Padoa-Schioppa, C. Neuronal origins of choice variability in economic decisions. Neuron 80, 1322–1336 (2013).

    Article  CAS  PubMed  Google Scholar 

  83. McDannald, M.A. et al. Orbitofrontal neurons acquire responses to ′valueless′ Pavlovian cues during unblocking. Elife 3, e02653 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Stalnaker, T.A. et al. Orbitofrontal neurons infer the value and identity of predicted outcomes. Nat. Commun. 5, 3926 (2014).

    Article  CAS  PubMed  Google Scholar 

  85. Knutson, B. & Gibbs, S.E.B. Linking nucleus accumbens dopamine and blood oxygenation. Psychopharmacology (Berl.) 191, 813–822 (2007).

    Article  CAS  Google Scholar 

  86. Maunsell, J.H. Neuronal representations of cognitive state: reward or attention? Trends Cogn. Sci. 8, 261–265 (2004).

    Article  PubMed  Google Scholar 

  87. Pearce, J.M., Kaye, H. & Hall, G. Predictive accuracy and stimulus associability: development of a model for Pavlovian learning. in Quantitative Analyses of Behavior (eds. M.L. Commons, R.J. Herrnstein & A.R. Wagner) 241–255 (Ballinger, 1982).

  88. Esber, G.R. & Haselgrove, M. Reconciling the influence of predictiveness and uncertainty on stimulus salience: a model of attention in associative learning. Proc. Biol. Sci. 278, 2553–2561 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Ogawa, M. et al. Risk-responsive orbitofrontal neurons track acquired salience. Neuron 77, 251–258 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. O'Neill, M. & Schultz, W. Coding of reward risk by orbitofrontal neurons is mostly distinct from coding of reward value. Neuron 68, 789–800 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Kepecs, A., Uchida, N., Zariwala, H.A. & Mainen, Z.F. Neural correlates, computation and behavioural impact of decision confidence. Nature 455, 227–231 (2008).

    Article  CAS  PubMed  Google Scholar 

  92. Leathers, M.L. & Olson, C.R. In monkeys making value-based decisions, LIP neurons encode cue salience and not action value. Science 338, 132–135 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Camille, N., Griffiths, C.A., Vo, K., Fellows, L.K. & Kable, J.W. Ventromedial frontal lobe damage disrupts value maximization in humans. J. Neurosci. 31, 7527–7532 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Fellows, L.K. & Farah, M.J. The role of ventromedial prefrontal cortex in decision making: judgment under uncertainty or judgment per se? Cereb. Cortex 17, 2669–2674 (2007).

    Article  PubMed  Google Scholar 

  95. Rudebeck, P.H. & Murray, E.A. Dissociable effects of subtotal lesions within the macaque orbital prefrontal cortex on reward-guided behavior. J. Neurosci. 31, 10569–10578 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. von Neumann, J. & Morgenstern, O. Theory of Games and Economic Behavior (Princeton University Press, 1947).

  97. Bunsey, M. & Eichenbaum, E. Conservation of hippocampal memory function in rats and humans. Nature 379, 255–257 (1996).

    Article  CAS  PubMed  Google Scholar 

  98. Burke, K.A., Franz, T.M., Miller, D.N. & Schoenbaum, G. The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards. Nature 454, 340–344 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Platt, M.L. & Glimcher, P.W. Neural correlates of decision variables in parietal cortex. Nature 400, 233–238 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Louie, K., Grattan, L.E. & Glimcher, P.W. Reward value-based gain control: divisive normalization in parietal cortex. J. Neurosci. 31, 10627–10639 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Cai, X. & Padoa-Schioppa, C. Neuronal encoding of subjective value in dorsal and ventral anterior cingulate cortex. J. Neurosci. 32, 3791–3808 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Hosokawa, T., Kennerley, S.W., Sloan, J. & Wallis, J.D. Single-neuron mechanisms underlying cost-benefit analysis in frontal cortex. J. Neurosci. 33, 17385–17397 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Watson, K.K. & Platt, M.L. Social signals in primate orbitofrontal cortex. Curr. Biol. 22, 2268–2273 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Roesch, M.R., Taylor, A.R. & Schoenbaum, G. Encoding of time-discounted rewards in orbitofrontal cortex is independent of value representation. Neuron 51, 509–520 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Blanchard, T.C., Hayden, B.Y. & Bromberg-Martin, E.S. Orbitofrontal cortex uses distinct codes for different choice attributes in decisions motivated by curiousity. Neuron (in the press).

  106. Schoenbaum, G., Takahashi, Y.K., Liu, T.L. & McDannald, M. Does the orbitofrontal cortex signal value? Ann. NY Acad. Sci. 1239, 87–99 (2011).

    Article  PubMed  Google Scholar 

  107. Gremel, C.M. & Costa, R.M. Orbitofrontal and striatal circuits dynamically encode the shift between goal-directed and habitual actions. Nat. Commun. 4, 2264 (2013).

    Article  CAS  PubMed  Google Scholar 

  108. McDannald, M.A., Lucantonio, F., Burke, K.A., Niv, Y. & Schoenbaum, G. Ventral striatum and orbitofrontal cortex are both required for model-based, but not model-free, reinforcement learning. J. Neurosci. 31, 2700–2705 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. McDannald, M.A., Saddoris, M.P., Gallagher, M. & Holland, P.C. Lesions of orbitofrontal cortex impair rats' differential outcome expectancy learning but not conditioned stimulus-potentiated feeding. J. Neurosci. 25, 4626–4632 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Machado, C.J. & Bachevalier, J. The effects of selective amygdala, orbital frontal cortex or hippocampal formation lesions on reward assessment in nonhuman primates. Eur. J. Neurosci. 25, 2885–2904 (2007).

    Article  PubMed  Google Scholar 

  111. Gottfried, J.A., O'Doherty, J. & Dolan, R.J. Encoding predictive reward value in human amygdala and orbitofrontal cortex. Science 301, 1104–1107 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  113. Pickens, C.L., Saddoris, M.P., Gallagher, M. & Holland, P.C. Orbitofrontal lesions impair use of cue-outcome associations in a devaluation task. Behav. Neurosci. 119, 317–322 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  114. West, E.A., DesJardin, J.T., Gale, K. & Malkova, L. Transient inactivation of orbitofrontal cortex blocks reinforcer devaluation in macaques. J. Neurosci. 31, 15128–15135 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Lak, A. et al. Orbitofrontal cortex is required for optimal waiting based on decision confidence. Neuron 84, 190–201 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Abe, H. & Lee, D. Distributed coding of actual and hypothetical outcomes in the orbital and dorsolateral prefrontal cortex. Neuron 70, 731–741 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Steiner, A.P. & Redish, A.D. Behavioral and neurophysiological correlates of regret in rat decision-making on a neuroeconomic task. Nat. Neurosci. 17, 995–1002 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Camille, N. et al. The involvement of the orbitofrontal cortex in the experience of regret. Science 304, 1167–1170 (2004).

    Article  CAS  PubMed  Google Scholar 

  119. Jones, J.L. et al. Orbitofrontal cortex supports behavior and learning using inferred but not cached values. Science 338, 953–956 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Rescorla, R.A. & Wagner, A.R. A theory of Pavlovian conditiong: variations in the effectiveness of reinforcement and nonreinforcement. in. Classical Conditioning II: Current Research and Theory (eds. A.H. Black & W.F. Prokesy) 64–99 (Appleton Century Crofts 1972).

  121. Pearce, J.M. & Hall, G. A model for Pavlovian learning: variations in the effectiveness of conditioned, but not of unconditioned, stimuli. Psychol. Rev. 87, 532–552 (1980).

    Article  CAS  PubMed  Google Scholar 

  122. Sutton, R.S. Learning to predict by the method of temporal difference. Mach. Learn. 3, 9–44 (1988).

    Google Scholar 

  123. Mirenowicz, J. & Schultz, W. Importance of unpredictability for reward responses in primate dopamine neurons. J. Neurophysiol. 72, 1024–1027 (1994).

    Article  CAS  PubMed  Google Scholar 

  124. Schultz, W., Dayan, P. & Montague, P.R. A neural substrate for prediction and reward. Science 275, 1593–1599 (1997).

    Article  CAS  PubMed  Google Scholar 

  125. Waelti, P., Dickinson, A. & Schultz, W. Dopamine responses comply with basic assumptions of formal learning theory. Nature 412, 43–48 (2001).

    Article  CAS  PubMed  Google Scholar 

  126. Pan, W.-X., Schmidt, R., Wickens, J.R. & Hyland, B.I. Dopamine cells respond to predicted events during classical conditioning: evidence for eligibility traces in the reward-learning network. J. Neurosci. 25, 6235–6242 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Roesch, M.R., Calu, D.J. & Schoenbaum, G. Dopamine neurons encode the better option in rats deciding between differently delayed or sized rewards. Nat. Neurosci. 10, 1615–1624 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Bayer, H.M. & Glimcher, P. Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron 47, 129–141 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Morris, G., Nevet, A., Arkadir, D., Vaadia, E. & Bergman, H. Midbrain dopamine neurons encode decisions for future action. Nat. Neurosci. 9, 1057–1063 (2006).

    Article  CAS  PubMed  Google Scholar 

  130. D'Ardenne, K., McClure, S.M., Nystrom, L.E. & Cohen, J.D. BOLD responses reflecting dopaminergic signals in the human ventral tegmental area. Science 319, 1264–1267 (2008).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  132. Tobler, P.N., O'Doherty, J., Dolan, R.J. & Schultz, W. Human neural learning depends on reward prediction errors in the blocking paradigm. J. Neurophysiol. 95, 301–310 (2006).

    Article  PubMed  Google Scholar 

  133. 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. Nat. Neurosci. 2, 11–12 (1999).

    Article  CAS  PubMed  Google Scholar 

  134. Sul, J.H., Kim, H., Huh, N., Lee, D. & Jung, M.W. Distinct roles of rodent orbitofrontal and medial prefrontal cortex in decision making. Neuron 66, 449–460 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wallis, J.D. & Rich, E.L. Challenges of interpreting frontal neurons during value-based decision-making. Front. Neurosci. 5, 124 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Takahashi, Y.K. et al. Neural estimates of imagined outcomes in the orbitofrontal cortex drive behavior and learning. Neuron 80, 507–518 (2013).

    Article  CAS  PubMed  Google Scholar 

  137. Schoenbaum, G., Roesch, M.R., Stalnaker, T.A. & Takahashi, Y.K. A new perspective on the role of the orbitofrontal cortex in adaptive behaviour. Nat. Rev. Neurosci. 10, 885–892 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Takahashi, Y.K. et al. Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex. Nat. Neurosci. 14, 1590–1597 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Wheeler, E.Z. & Fellows, L.K. The human ventromedial frontal lobe is critical for learning from negative feedback. Brain 131, 1323–1331 (2008).

    Article  PubMed  Google Scholar 

  140. Walton, M.E., Behrens, T.E., Noonan, M.P. & Rushworth, M.F. Giving credit where credit is due: orbitofrontal cortex and valuation in an uncertain world. Ann. NY Acad. Sci. 1239, 14–24 (2011).

    Article  PubMed  Google Scholar 

  141. Thorndike, E.L. A proof of the law of effect. Science 77, 173–175 (1933).

    Article  CAS  PubMed  Google Scholar 

  142. Tolman, E.C. There is more than one kind of learning. Psychol. Rev. 56, 144–155 (1949).

    Article  CAS  PubMed  Google Scholar 

  143. Wilson, R.C., Takahashi, Y.K., Schoenbaum, G. & Niv, Y. Orbitofrontal cortex as a cognitive map of task space. Neuron 81, 267–279 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Deacon, T.W., Eichenbaum, H., Rosenberg, P. & Eckmann, K.W. Afferent connections of the perirhinal cortex in the rat. J. Comp. Neurol. 220, 168–190 (1983).

    Article  CAS  PubMed  Google Scholar 

  145. Voorn, P., Vanderschuren, L.J.M.J., Groenewegen, H.J., Robbins, T.W. & Pennartz, C.M.A. Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci. 27, 468–474 (2004).

    Article  CAS  PubMed  Google Scholar 

  146. Groenewegen, H.J., Berendse, H.W., Wolters, J.G. & Lohman, A.H.M. The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. Prog. Brain Res. 85, 95–116 (1990).

    Article  CAS  PubMed  Google Scholar 

  147. Klein-Flügge, M.C., Barron, H.C., Brodersen, K.H., Dolan, R.J. & Behrens, T.E. Segregated encoding of reward-identity and stimulus-reward associations in human orbitofrontal cortex. J. Neurosci. 33, 3202–3211 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Schoenbaum, G. & Eichenbaum, H. Information coding in the rodent prefrontal cortex. I. Single-neuron activity in orbitofrontal cortex compared with that in pyriform cortex. J. Neurophysiol. 74, 733–750 (1995).

    Article  CAS  PubMed  Google Scholar 

  149. Ongür, 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).

    Article  PubMed  Google Scholar 

  150. Schoenbaum, G., Setlow, B. & Gallagher, M. Orbitofrontal cortex: modeling prefrontal function in rats. in The Neuropsychology of Memory (eds. L. Squire & D. Schacter) 463–477 (Guilford Press, 2002).

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Acknowledgements

The authors would like to thank C. Padoa-Schioppa, J. Wallis and P. Rudebeck for critical readings of earlier versions. This work was supported by grants to G.S. from the National Institute on Drug Abuse, the National Institute of Mental Health and the National Institute on Aging while G.S. was employed at the University of Maryland, Baltimore, and by funding from the National Institute on Drug Abuse at the Intramural Research Program. The opinions expressed in this article are the authors' own and do not reflect the view of the US National Institutes of Health, the Department of Health and Human Services, or the United States government.

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Stalnaker, T., Cooch, N. & Schoenbaum, G. What the orbitofrontal cortex does not do. Nat Neurosci 18, 620–627 (2015). https://doi.org/10.1038/nn.3982

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