Dissociable roles of medial orbitofrontal cortex in human operant extinction learning
Open accessAbstract
Operant extinction, which features modification of instrumental responses to stimuli following a change in associated reinforcement, is an important form of learning for organisms in dynamic environments. Animal studies have highlighted orbital and medial prefrontal cortex and amygdala as mediators of operant extinction. Yet little is known about the neural mediators of operant extinction learning in humans. Using a novel fMRI paradigm, we report dissociable functional responses in distinct regions of medial orbitofrontal cortex (mOFC) during successful appetitive and aversive based operant extinction. During successful operant extinction, increased activity was observed in frontopolar OFC, while decreased activity was observed in caudal mOFC and rostral anterior cingulate cortex (rACC) relative to both (i) successful control trials where the reinforcement associated with the stimulus does not change; and (ii) successful acquisition trials during initial learning of the stimulus-reinforcement associations. Functional connectivity analysis demonstrated inverse connectivity between frontopolar OFC and both rACC and the amygdala. These data support animal models suggesting the importance of mOFC-amygdala interaction during operant extinction and expand our knowledge of the neural systems in humans. These findings suggest that in humans, frontopolar OFC modulates activity in caudal mOFC, rACC and amygdala during successful operant extinction learning.
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Animal and human work show that vmPFC is critical for fear extinction and reversal learning.
“Second, animal and human work show that vmPFC is critical for fear extinction and reversal learning (Milad et al. 2007;Finger et al. 2008;Schiller et al. 2008).”
From Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies (2014) · cites this paper as Finger et al. 2008
The Discussion reports medial orbitofrontal activity during human operant extinction, while the paper describes animal and human evidence linking medial prefrontal regions to fear-extinction recall and medial orbitofrontal regions to reversal learning (page numbers unavailable). It does not establish that vmPFC is critical for both fear extinction and reversal learning: its own experiment tested operant extinction, and it describes the fear and reversal findings more cautiously. (LLM, conf=0.85)
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BackgroundThe Neurobiological Underpinnings of Psychopathy
Brito, S. A. D., & Mitchell, I. (2018) · doi:10.1002/9781118650868.ch9 · Cited by 4 · see citing works
Jenni, N. L., Symonds, N. E., & Floresco, S. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06265-8 · Cited by 3 · see citing works
Kutz, A. M. (2016) · DigitalCommons (California Polytechnic State University) · Cited by 2 · see citing works
The Neural Substrates of Fear Extinction
Lueken, U., & Maslowski, N. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3342-2_5 · Cited by 2 · see citing works
Li, C., & Tsai, C. (2021) · arXiv (Cornell University) · doi:10.48550/arxiv.2104.10957
Operant behavior is reliably impaired in a mouse model of Angelman syndrome
Guoynes, C. D., Kerr, D. D., Hotait, Z. S., Tanas, J. K., & Sidorov, M. S. (2026) · Scientific Reports · doi:10.1038/s41598-026-71483-5
- Authors
- Finger, E. C., Mitchell, D. G. V., Jones, M., & Blair, R. J. R.
- Affiliations
- Western University (CA)
- National Institutes of Health (US)
- Corresponding author
- Finger, Elizabeth C.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 43
- Issue
- 4
- Pages
- 748-755
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3941699
- OpenAlex
- W1988482203
- Cited by
- 45
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 6 · 2012: 3
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- operant extinction, medial orbitofrontal cortex, rostral anterior cingulate cortex, amygdala, operant conditioning, functional connectivity, reinforcement learning
- MeSH terms
- Adult, Brain Mapping, Conditioning, Operant, Discrimination Learning, Extinction, Psychological, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male
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