Controlling one’s world: Identification of sub-regions of primate PFC underlying goal-directed behavior
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Abstract
Impaired detection of causal relationships between actions and their outcomes can lead to maladaptive behavior. However, causal roles of specific prefrontal cortex (PFC) sub-regions and the caudate nucleus in mediating such relationships in primates are unclear. We inactivated and overactivated five PFC sub-regions, reversibly and pharmacologically: areas 24 (perigenual anterior cingulate cortex), 32 (medial PFC), 11 (anterior orbitofrontal cortex, OFC), 14 (rostral ventromedial PFC/medial OFC), and 14-25 (caudal ventromedial PFC) and the anteromedial caudate to examine their role in expressing learned action-outcome contingencies using a contingency degradation paradigm in marmoset monkeys. Area 24 or caudate inactivation impaired the response to contingency change, while area 11 inactivation enhanced it, and inactivation of areas 14, 32, or 14-25 had no effect. Overactivation of areas 11 and 24 impaired this response. These findings demonstrate the distinct roles of PFC sub-regions in goal-directed behavior and illuminate the candidate neurobehavioral substrates of psychiatric disorders, including obsessive-compulsive disorder.
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OFC's functional significance in goal-directed decision-making has been controversial; both activation and inhibition of OFC disrupt flexibility of behavior and shift it to habitual.
“In contrast to the ACC, although a number of studies implicate the OFC in reward-related decision-making, its functional significance in goal-directed decision-making has been controversial; both activation and inhibition of the OFC disrupt flexibility of a behavior and shift it to a habitual one5,44.”
From Dissociable roles of prefrontal plasticity in decision-making strategy and execution of habitual behavior (2026) · cites this paper as [44]
The Results section reports that overactivation of anterior OFC (area 11) blunted sensitivity to action–outcome contingency degradation, but inactivation enhanced it rather than disrupting it. The Discussion’s Implications section also cautions that persistent responding during degradation is not necessarily habitual control, so the claimed shift to habit is not established. Page numbers were not supplied in our copy. (LLM, conf=0.90)
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Permutation Tests for Random Effects in Linear Mixed Models
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The orbitofrontal cortex, predicted value and choice
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Vaghi, M. M. S., Cardinal, R. N., Apergis-Schoute, A. M., Fineberg, N. A., Sule, A., & Robbins, T. W. (2018) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2018.09.014 · Cited by 67 · see citing works
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Evidence for Segregated and Integrative Connectivity Patterns in the Human Basal Ganglia
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Prefrontal Regulation of Threat-Elicited Behaviors: A Pathway to Translation
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Effects of Striatal GABAA-Receptor Blockade on Striatal and Cortical Activity in Monkeys
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The Role of Habits in Maladaptive Behaviour and Therapeutic Interventions
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Bradfield, L. A., Morris, R. W., & Balleine, B. W. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780190228163.003.0031 · Cited by 4 · see citing works
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- Authors
- Duan, L. Y., Horst, N. K., Cranmore, S. A. W., Horiguchi, N., Cardinal, R. N., Roberts, A. C., & Robbins, T. W.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Duan, Lisa Y.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 109
- Issue
- 15
- Pages
- 2485-2498.e5
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC8346232
- OpenAlex
- W3176985371
- Cited by
- 41
- References
- 124
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 10 · 2023: 5 · 2022: 6 · 2021: 4
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (106431/Z/14/Z, 104631/Z/14/Z)
- Medical Research Council
- 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
- goal-directed behavior, action-outcome contingency, contingency degradation, pregenual anterior cingulate cortex, medial prefrontal cortex, ventromedial prefrontal cortex, caudate nucleus, marmoset monkey, neural inactivation, obsessive-compulsive disorder, mental illness
- MeSH terms
- Animals, Behavior, Animal, Callithrix, Goals, Learning, Prefrontal Cortex
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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