The Orbitofrontal Cortex and Ventral Tegmental Area Are Necessary for Learning from Unexpected Outcomes

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2009 May 5

PMID 19409271

Citations 163

Authors

Yuji K Takahashi

Matthew R Roesch

Thomas A Stalnaker

Richard Z Haney

Donna J Calu

Adam R Taylor

Kathryn A Burke

Geoffrey Schoenbaum

Affiliations

Soon will be listed here.

Abstract

Humans and other animals change their behavior in response to unexpected outcomes. The orbitofrontal cortex (OFC) is implicated in such adaptive responding, based on evidence from reversal tasks. Yet these tasks confound using information about expected outcomes with learning when those expectations are violated. OFC is critical for the former function; here we show it is also critical for the latter. In a Pavlovian overexpectation task, inactivation of OFC prevented learning driven by unexpected outcomes, even when performance was assessed later. We propose this reflects a critical contribution of outcome signaling by OFC to encoding of reward prediction errors elsewhere. In accord with this proposal, we report that signaling of reward predictions by OFC neurons was related to signaling of prediction errors by dopamine neurons in ventral tegmental area (VTA). Furthermore, bilateral inactivation of VTA or contralateral inactivation of VTA and OFC disrupted learning driven by unexpected outcomes.

Citing Articles

Neuromodulation of Dopamine D2 Receptors Alters Orbitofrontal Neuronal Activity and Reduces Risk-Prone Behavior in Male Rats with Inflammatory Pain.

Dourado M, Cardoso-Cruz H, Monteiro C, Galhardo V Mol Neurobiol. 2025; .

PMID: 39985709 DOI: 10.1007/s12035-025-04781-0.

The potential of muscarinic M and M receptor activators for the treatment of cognitive impairment associated with schizophrenia.

Yohn S, Harvey P, Brannan S, Horan W Front Psychiatry. 2024; 15:1421554.

PMID: 39483736 PMC: 11525114. DOI: 10.3389/fpsyt.2024.1421554.

Prior cocaine use diminishes encoding of latent information by orbitofrontal, but not medial, prefrontal ensembles.

Mueller L, Konya C, Sharpe M, Wikenheiser A, Schoenbaum G Curr Biol. 2024; 34(22):5223-5238.e3.

PMID: 39454572 PMC: 11576232. DOI: 10.1016/j.cub.2024.09.064.

Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States.

Ottenheimer D, Vitale K, Ambroggi F, Janak P, Saunders B J Neurosci. 2024; 44(46).

PMID: 39353730 PMC: 11561866. DOI: 10.1523/JNEUROSCI.0013-24.2024.

Predictive filtering of sensory response via orbitofrontal top-down input.

Tsukano H, Garcia M, Garcia M, Dandu P, Dandu P, Kato H bioRxiv. 2024; .

PMID: 39345607 PMC: 11429993. DOI: 10.1101/2024.09.17.613562.

References

Chudasama Y, Kralik J, Murray E . Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task. Cereb Cortex. 2006; 17(5):1154-9. DOI: 10.1093/cercor/bhl025. View

Gallagher M, McMahan R, Schoenbaum G . Orbitofrontal cortex and representation of incentive value in associative learning. J Neurosci. 1999; 19(15):6610-4. PMC: 6782791. View

Holland P, Gallagher M . Amygdala central nucleus lesions disrupt increments, but not decrements, in conditioned stimulus processing. Behav Neurosci. 1993; 107(2):246-53. DOI: 10.1037//0735-7044.107.2.246. View

ODoherty J, Dayan P, Schultz J, Deichmann R, Friston K, Dolan R . Dissociable roles of ventral and dorsal striatum in instrumental conditioning. Science. 2004; 304(5669):452-4. DOI: 10.1126/science.1094285. View

Montague P, Dayan P, Sejnowski T . A framework for mesencephalic dopamine systems based on predictive Hebbian learning. J Neurosci. 1996; 16(5):1936-47. PMC: 6578666. View

ODoherty J, Deichmann R, Critchley H, Dolan R . Neural responses during anticipation of a primary taste reward. Neuron. 2002; 33(5):815-26. DOI: 10.1016/s0896-6273(02)00603-7. View

Murschall A, Hauber W . Inactivation of the ventral tegmental area abolished the general excitatory influence of Pavlovian cues on instrumental performance. Learn Mem. 2006; 13(2):123-6. DOI: 10.1101/lm.127106. View

Hatfield T, Han J, Conley M, Gallagher M, Holland P . Neurotoxic lesions of basolateral, but not central, amygdala interfere with Pavlovian second-order conditioning and reinforcer devaluation effects. J Neurosci. 1996; 16(16):5256-65. PMC: 6579315. View

Izquierdo A, Suda R, Murray E . Bilateral orbital prefrontal cortex lesions in rhesus monkeys disrupt choices guided by both reward value and reward contingency. J Neurosci. 2004; 24(34):7540-8. PMC: 6729636. DOI: 10.1523/JNEUROSCI.1921-04.2004. View

10.

Wheeler E, Fellows L . The human ventromedial frontal lobe is critical for learning from negative feedback. Brain. 2008; 131(Pt 5):1323-31. DOI: 10.1093/brain/awn041. View

11.

Arana F, Parkinson J, Hinton E, Holland A, Owen A, Roberts A . Dissociable contributions of the human amygdala and orbitofrontal cortex to incentive motivation and goal selection. J Neurosci. 2003; 23(29):9632-8. PMC: 6740473. View

12.

Niv Y, Daw N, Joel D, Dayan P . Tonic dopamine: opportunity costs and the control of response vigor. Psychopharmacology (Berl). 2006; 191(3):507-20. DOI: 10.1007/s00213-006-0502-4. View

13.

Izquierdo A, Murray E . Opposing effects of amygdala and orbital prefrontal cortex lesions on the extinction of instrumental responding in macaque monkeys. Eur J Neurosci. 2005; 22(9):2341-6. DOI: 10.1111/j.1460-9568.2005.04434.x. View

14.

Bayer H, Glimcher P . Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron. 2005; 47(1):129-41. PMC: 1564381. DOI: 10.1016/j.neuron.2005.05.020. View

15.

Burke K, Franz T, Miller D, Schoenbaum G . The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards. Nature. 2008; 454(7202):340-4. PMC: 2727745. DOI: 10.1038/nature06993. View

16.

Pickens C, Saddoris M, Setlow B, Gallagher M, Holland P, Schoenbaum G . Different roles for orbitofrontal cortex and basolateral amygdala in a reinforcer devaluation task. J Neurosci. 2003; 23(35):11078-84. PMC: 6741041. View

17.

Hornak J, ODoherty J, Bramham J, Rolls E, Morris R, Bullock P . Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans. J Cogn Neurosci. 2004; 16(3):463-78. DOI: 10.1162/089892904322926791. View

18.

Gottfried J, ODoherty J, Dolan R . Encoding predictive reward value in human amygdala and orbitofrontal cortex. Science. 2003; 301(5636):1104-7. DOI: 10.1126/science.1087919. View

19.

Hare T, ODoherty J, Camerer C, Schultz W, Rangel A . Dissociating the role of the orbitofrontal cortex and the striatum in the computation of goal values and prediction errors. J Neurosci. 2008; 28(22):5623-30. PMC: 6670807. DOI: 10.1523/JNEUROSCI.1309-08.2008. View

20.

Roesch M, Taylor A, Schoenbaum G . Encoding of time-discounted rewards in orbitofrontal cortex is independent of value representation. Neuron. 2006; 51(4):509-20. PMC: 2561990. DOI: 10.1016/j.neuron.2006.06.027. View