Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making
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Significance: Fear of negative outcomes has a powerful adverse influence on decision making in anxiety disorders. Although neuroimaging studies of patients with anxiety disorders have revealed dysregulation in numerous frontal brain regions including the orbitofrontal and ventrolateral prefrontal cortex, the causal involvement of this dysregulation is unknown. Here we demonstrate that in the marmoset monkey, inactivation of anterior orbitofrontal or ventrolateral prefrontal cortex increases negative bias in decision making via two distinct cognitive mechanisms—elevated uncertainty and attentional disruption, respectively. These findings provide, to our knowledge, the first direct evidence that dysregulation of distinct neurocognitive mechanisms within the prefrontal cortex may underlie the mixed etiology of anxiety disorders. Such insight will allow the development of more precise diagnostics and individually tailored therapeutic approaches.
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Inactivation of area 11 induces negative biases based on memory of experiences, dependent on OFC interaction with amygdala and anterior hippocampus.
“Conversely, inactivation of area 11 only induces negative biases based on the memory of those experiences, memories dependent on the OFC's interaction with the amygdala and anterior hippocampus [38].”
From Prefrontal cortex and depression (2022) · cites this paper as [38]
Inactivation of rostral central OFC (primarily area 11) and vlPFC in marmosets induces a negative bias in decision making.
“Inactivation of more rostral regions of the central OFC (primarily area 11) and vlPFC in marmosets also induce a negative bias in decision making [38], although likely the result of distinct underlying psychological mechanisms.”
From Prefrontal cortex and depression (2022) · cites this paper as [38]
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Harkins, H. E., Christopher, K., Matrov, D., Ingram, I. D., Saglio, E. B., Dold, G. R., & Chudasama, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.18.688868
Home-cage pharmacology in marmosets: behavioral effects of scopolamine
Harkins, H. E., Christopher, K., Matrov, D., Ingram, I. D., Saglio, E. B., Dold, G. R., & Chudasama, Y. (2026) · Psychopharmacology · doi:10.1007/s00213-026-07054-3
- Authors
- Clarke, H. F., Horst, N. K., & Roberts, A. C.
- Affiliations
- University of Cambridge (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-03-16
- Volume
- 112
- Issue
- 13
- Pages
- 4176-4181
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4386364
- OpenAlex
- W1977084018
- Cited by
- 52
- References
- 45
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2022: 3 · 2021: 7 · 2020: 3 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 6 · 2014: 1
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (acceptedVersion, cc-by-nc)
- Funders
- Medical Research Council (G0901884, RG62920)
- 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
- ventral prefrontal cortex, orbitofrontal cortex, ventrolateral prefrontal cortex, anxiety, decision-making, punishment avoidance, approach-avoidance task, marmoset monkey, amygdala, anterior hippocampus, anxiolytic treatment, attentional control, anxiety disorders
- MeSH terms
- Amygdala, Animals, Anxiety Disorders, Attention, Behavior, Animal, Callithrix, Decision Making, Female, Hippocampus, Magnetic Resonance Imaging, Male, Anti-Anxiety Agents, Vision, Ocular, Bias, Prefrontal Cortex, Neuroimaging
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