The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards


Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald’s Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways1, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction2,3. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making4, was critical for the former but not for the latter form of conditioned reinforcement.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Effect of orbitofrontal lesions on pavlovian conditioning and reinforcer devaluation.
Figure 2: Effect of orbitofrontal lesions on conditioned reinforcement for a fully conditioned A cue, for a blocked X cue, and for the partially blocked Y cue before and after reinforcer devaluation.
Figure 3: Effect of orbitofrontal lesions on pavlovian conditioned responding after transreinforcer blocking in extinction probe tests.


  1. 1

    Robinson, T. N., Borzekowski, D. L., Matheson, D. M. & Kraemer, H. C. Effects of fast food branding on young children’s taste preferences. Arch. Pediatr. Adolesc. Med. 161, 792–797 (2007)

    Article  Google Scholar 

  2. 2

    Shaham, Y., Shalev, U., Lu, L., de Wit, H. & Stewart, J. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl.) 168, 3–20 (2003)

    Article  Google Scholar 

  3. 3

    O’Brien, C. P. Anticraving medications for relapse prevention: a possible new class of psychoactive medications. Am. J. Psychiatry 162, 1423–1431 (2005)

    Article  Google Scholar 

  4. 4

    Murray, E. A., O’Doherty, J. P. & Schoenbaum, G. What we know and do not know about the functions of the orbitofrontal cortex after 20 years of cross-species studies. J. Neurosci. 27, 8166–8169 (2007)

    Article  Google Scholar 

  5. 5

    Rescorla, R. A. Learning about qualitatively different outcomes during a blocking procedure. Anim. Learn. Behav. 27, 140–151 (1999)

    Article  Google Scholar 

  6. 6

    Ganesan, R. & Pearce, J. M. Effect of changing the unconditioned stimulus on appetitive blocking. J. Exp. Psychol. Anim. Behav. Process. 14, 280–291 (1988)

    Article  Google Scholar 

  7. 7

    Weissenborn, R., Robbins, T. W. & Everitt, B. J. Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats. Psychopharmacology (Berl.) 134, 242–257 (1997)

    Article  Google Scholar 

  8. 8

    Pears, A., Parkinson, J. A., Hopewell, L., Everitt, B. J. & Roberts, A. C. Lesions of the orbitofrontal but not medial prefrontal cortex disrupt conditioned reinforcement in primates. J. Neurosci. 23, 11189–11201 (2003)

    Article  Google Scholar 

  9. 9

    Parkinson, J. A., Roberts, A. C., Everitt, B. J. & Di Ciano, P. Acquisition of instrumental conditioned reinforcement is resistant to the devaluation of the unconditioned stimulus. Q. J. Exp. Psychol. 58, 19–30 (2005)

    Article  Google Scholar 

  10. 10

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

    ADS  Article  Google Scholar 

  11. 11

    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  Google Scholar 

  12. 12

    Feierstein, C. E., Quirk, M. C., Uchida, N., Sosulski, D. L. & Mainen, Z. F. Representation of spatial goals in rat orbitofrontal cortex. Neuron 51, 495–507 (2006)

    Article  Google Scholar 

  13. 13

    O’Doherty, J. P., Deichmann, R., Critchley, H. D. & Dolan, R. J. Neural responses during anticipation of a primary taste reward. Neuron 33, 815–826 (2002)

    Article  Google Scholar 

  14. 14

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

    ADS  Article  Google Scholar 

  15. 15

    Tremblay, L. & Schultz, W. Relative reward preference in primate orbitofrontal cortex. Nature 398, 704–708 (1999)

    ADS  Article  Google Scholar 

  16. 16

    Roesch, M. R. & Olson, C. R. Neuronal activity related to reward value and motivation in primate frontal cortex. Science 304, 307–310 (2004)

    ADS  Article  Google Scholar 

  17. 17

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

    Article  Google Scholar 

  18. 18

    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  Google Scholar 

  19. 19

    Pickens, C. L. et al. Different roles for orbitofrontal cortex and basolateral amygdala in a reinforcer devaluation task. J. Neurosci. 23, 11078–11084 (2003)

    Article  Google Scholar 

  20. 20

    Setlow, B., Holland, P. C. & Gallagher, M. Disconnection of the basolateral amygdala complex and nucleus accumbens impairs appetitive Pavlovian second-order conditioned responses. Behav. Neurosci. 116, 267–275 (2002)

    Article  Google Scholar 

  21. 21

    Taylor, J. R. & Robbins, T. W. Enhanced behavioral control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology (Berl.) 84, 405–412 (1984)

    Article  Google Scholar 

  22. 22

    Cousens, G. A. & Otto, T. Neural substrates of olfactory discrimination learning with auditory secondary reinforcement. I. Contributions of the basolateral amygdaloid complex and orbitofrontal cortex. Integr. Physiol. Behav. Sci. 38, 272–294 (2003)

    Article  Google Scholar 

  23. 23

    Parkinson, J. A. et al. The role of the primate amygdala in conditioned reinforcement. J. Neurosci. 21, 7770–7780 (2001)

    Article  Google Scholar 

  24. 24

    Setlow, B., Gallagher, M. & Holland, P. C. The basolateral complex of the amygdala is necessary for acquisition but not expression of CS motivational value in appetitive Pavlovian second-order conditioning. Eur. J. Neurosci. 15, 1841–1853 (2002)

    Article  Google Scholar 

  25. 25

    Robledo, P., Robbins, T. W. & Everitt, B. J. Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine. Behav. Neurosci. 110, 981–990 (1996)

    Article  Google Scholar 

  26. 26

    Parkinson, J. A., Olmstead, M. C., Burns, L. H., Robbins, T. W. & Everitt, B. J. Dissociation of effects of lesions of the nucleus accumbens core and shell on appetitive Pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by d-amphetamine. J. Neurosci. 19, 2401–2411 (1999)

    Article  Google Scholar 

  27. 27

    Cador, M., Robbins, T. W. & Everitt, B. J. Involvement of the amygdala in stimulus–reward associations: interactions with the ventral striatum. Neuroscience 30, 77–86 (1989)

    Article  Google Scholar 

  28. 28

    Hall, J., Parkinson, J. A., Connor, T. M., Dickinson, A. & Everitt, B. J. Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behavior. Eur. J. Neurosci. 13, 1984–1992 (2001)

    Article  Google Scholar 

  29. 29

    Balleine, B. W. & Corbit, L. H. Double dissociation of nucleus accumbens core and shell on the general and outcome-specific forms of pavlovian-instrumental transfer. Soc. Neurosci. Abstr. 71 16. (2005)

  30. 30

    Corbit, L. H. & Balleine, B. W. Double dissociation of basolateral and central amygdala lesions on the general and outcome-specific forms of pavlovian-instrumental transfer. J. Neurosci 25, 962–970 (2005)

    Article  Google Scholar 

Download references


We are grateful to A. Delamater and P. Holland for their advice on this work. This work was supported by the National Institute on Drug Abuse (NIDA).

Author Contributions K.A.B. and G.S. conceived the experiments; K.A.B., D.N.M. and T.M.F. carried out the experiments; K.A.B. and G.S. analysed the data and co-wrote the manuscript with assistance from each of the other authors.

Author information



Corresponding author

Correspondence to Geoffrey Schoenbaum.

Supplementary information

Supplementary Information

The file contains Supplementary Results and Supplementary Figures S1-S5 with Legends. (PDF 687 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Burke, K., Franz, T., Miller, D. et al. The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards. Nature 454, 340–344 (2008).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.