What the orbitofrontal cortex does not do

Stalnaker, Thomas A; Cooch, Nisha K; Schoenbaum, Geoffrey

doi:10.1038/nn.3982

Cited by 532Neural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on BehaviorMemory and Neural Mechanisms

What the orbitofrontal cortex does not do

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Stalnaker, Thomas A, Cooch, Nisha K, Schoenbaum, Geoffrey·2015·Nature Neuroscience

DOI 10.1038/nn.3982PMC PMC5541252

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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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The importance of OFC in reward processing has been challenged.
“However, the importance of the OFC has been challenged in this and other work (Berridge and Kringelbach, 2008; Stalnaker et al., 2015).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Stalnaker et al., 2015

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Human neural learning depends on reward prediction errors in the blocking paradigm.
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Category-dependent and category-independent goal-value codes in human ventromedial prefrontal cortex
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The involvement of the orbitofrontal cortex in learning under changing task contingencies.
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Neuronal Encoding of Subjective Value in Dorsal and Ventral Anterior Cingulate Cortex
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Beyond reversal: a critical role for human orbitofrontal cortex in flexible learning from probabilistic feedback
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APCCdh1 mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity
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Modification of the Backlin-Kirk Combustion Chamber for Micro-Determination of Carbon and Lipoids
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Dissociable Effects of Subtotal Lesions within the Macaque Orbital Prefrontal Cortex on Reward-Guided Behavior
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Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement
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Lesions of the Basolateral Amygdala and Orbitofrontal Cortex Differentially Affect Acquisition and Performance of a Rodent Gambling Task
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Orbitofrontal Lesions Impair Use of Cue-Outcome Associations in a Devaluation Task.
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Transient Inactivation of Orbitofrontal Cortex Blocks Reinforcer Devaluation in Macaques
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Segregated Encoding of Reward–Identity and Stimulus–Reward Associations in Human Orbitofrontal Cortex
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Different Time Courses for Learning-Related Changes in Amygdala and Orbitofrontal Cortex
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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
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Social Signals in Primate Orbitofrontal Cortex
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Orbitofrontal cortex lesions disrupt risk assessment in a novel serial decision-making task for rats.
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The human ventromedial frontal lobe is critical for learning from negative feedback
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Model‐based learning and the contribution of the orbitofrontal cortex to the model‐free world
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Abnormal associative encoding in orbitofrontal neurons in cocaine‐experienced rats during decision‐making
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Neural Estimates of Imagined Outcomes in the Orbitofrontal Cortex Drive Behavior and Learning
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Lesions of Orbitofrontal Cortex Impair Rats' Differential Outcome Expectancy Learning But Not Conditioned Stimulus-Potentiated Feeding
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Orbitofrontal inactivation impairs reversal of Pavlovian learning by interfering with ‘disinhibition’ of responding for previously unrewarded cues
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Risk-Responsive Orbitofrontal Neurons Track Acquired Salience
Ogawa, M., van der Meer, M. A. A., Esber, G. R., Cerri, D. H., Stalnaker, T. A., & Schoenbaum, G. (2013) · Neuron · doi:10.1016/j.neuron.2012.11.006 · Cited by 74 · see citing works
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Reward Stability Determines the Contribution of Orbitofrontal Cortex to Adaptive Behavior
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Orbitofrontal neurons acquire responses to ‘valueless’ Pavlovian cues during unblocking
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Selective Aspiration or Neurotoxic Lesions of Orbital Frontal Areas 11 and 13 Spared Monkeys' Performance on the Object Discrimination Reversal Task
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Rhesus Monkeys with Orbital Prefrontal Cortex Lesions Can Learn to Inhibit Prepotent Responses in the Reversed Reward Contingency Task
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Challenges of Interpreting Frontal Neurons during Value-Based Decision-Making
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Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats
West, E. A., Forcelli, P. A., McCue, D. L., & Málková, L. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.02.027 · Cited by 37 · see citing works

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[96]von Neumann J Morgenstern O Theory of Games and Economic Behavior Princeton University Press 1947
[150]Schoenbaum G Setlow B Gallagher M Orbitofrontal cortex: modeling prefrontal function in rats The Neuropsychology of Memory Squire L Schacter D 463 477 Guilford Press 2002

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Frontal cortex neuron types categorically encode single decision variables
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Medial Orbitofrontal Cortex Mediates Outcome Retrieval in Partially Observable Task Situations
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The sensation of groove engages motor and reward networks
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Multifaceted Contributions by Different Regions of the Orbitofrontal and Medial Prefrontal Cortex to Probabilistic Reversal Learning
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Direct electrical stimulation of lateral orbitofrontal cortex acutely improves mood in individuals with symptoms of depression
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Specializations for reward-guided decision-making in the primate ventral prefrontal cortex
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Single-cell activity tracking reveals that orbitofrontal neurons acquire and maintain a long-term memory to guide behavioral adaptation
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Evolving schema representations in orbitofrontal ensembles during learning
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Values encoded in orbitofrontal cortex are causally related to economic choices
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Midbrain dopamine neurons compute inferred and cached value prediction errors in a common framework
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Taking stock of value in the orbitofrontal cortex
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Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals
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A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control
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Two Anatomically and Computationally Distinct Learning Signals Predict Changes to Stimulus-Outcome Associations in Hippocampus
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The case against economic values in the orbitofrontal cortex (or anywhere else in the brain).
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An Integrated Model of Action Selection: Distinct Modes of Cortical Control of Striatal Decision Making
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Authors: Stalnaker, T. A., Cooch, N. K., & Schoenbaum, G.
Affiliations: National Institutes of Health (US)
Corresponding author: Schoenbaum, Geoffrey
ORCID: Stalnaker, Thomas A
Cooch, Nisha K
Schoenbaum, Geoffrey
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2015-04-28
Volume: 18
Issue: 5
Pages: 620-627
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.3982
PMC: PMC5541252
OpenAlex: W2020689320
Cited by: 531
References: 147
Citations by year: 2026: 15 · 2025: 41 · 2024: 45 · 2023: 34 · 2022: 45 · 2021: 59 · 2020: 77 · 2019: 55 · 2018: 60 · 2017: 33 · 2016: 50 · 2015: 16
FWCI: 5.27
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Health and Human Services
National Institutes of Health (Z99 DA999999)
National Institute on Aging
National Institute of Mental Health
National Institute on Drug Abuse (ZIADA000587)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: orbitofrontal cortex, neuropsychiatric disorders, cognitive neuroscience
MeSH terms: Animals, Brain Mapping, Decision Making, Emotions, Humans, Inhibition, Psychological, Judgment, Learning, Models, Neurological, Models, Psychological, Primates, Reward, Prefrontal Cortex, Rats

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