ArticlePLoS biology2020
Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Evolution of the frontal aslant tract and implications for primate vocalization and human speech.Nature communications · 2026Article
- The macaque ventral intraparietal functional connectivity patterns reveal an anterio-posterior specialization mirroring that described in human ventral intraparietal area.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- Decision-making shapes dynamic inter-areal communication within macaque ventral frontal cortex.Current biology : CB · 2024Article
- Aspiration removal of orbitofrontal cortex disrupts cholinergic fibers of passage to anterior cingulate cortex in rhesus macaques.Brain structure & function · 2024Article
- Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated geneNational science review · 2023Article
- An open resource combining multi-contrast MRI and microscopy in the macaque brain.Nature communications · 2023Article
- Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala.Brain structure & function · 2023Review
- Local and global reward learning in the lateral frontal cortex show differential development during human adolescence.PLoS biology · 2023Article
- Prefrontal influences on the function of the neural circuitry underlying anxious temperament in primates.Oxford open neuroscience · 2023Article
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- Chronic Intermittent Ethanol Administration during Adolescence Produces Sex Dependent Impairments in Behavioral Flexibility and Survivability.Brain sciences · 2022Article
- Interactions between ventrolateral prefrontal and anterior cingulate cortex during learning and behavioural change.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Ultrasound modulation of macaque prefrontal cortex selectively alters credit assignment-related activity and behavior.Science advances · 2021Article
- Expression of human-specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility.The EMBO journal · 2021Article
- Defining an orbitofrontal compass: Functional and anatomical heterogeneity across anterior-posterior and medial-lateral axes.Behavioral neuroscience · 2021Review
- The orbitofrontal cortex in temporal cognition.Behavioral neuroscience · 2021Review
- Impact of internal and external factors on prosocial choices in rhesus macaques.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Article
- Atypical Neural Responses of Cognitive Flexibility in Parents of Children With Autism Spectrum Disorder.Frontiers in neuroscience · 2021Article
- Global reward state affects learning and activity in raphe nucleus and anterior insula in monkeys.Nature communications · 2020Article
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Authors and funding
17 authors at 5 institutions in 5 countries.
Funding
Abstract
One of the most influential accounts of central orbitofrontal cortex-that it mediates behavioral flexibility-has been challenged by the finding that discrimination reversal in macaques, the classic test of behavioral flexibility, is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests that the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity, a group of nine macaques were taught discrimination reversal learning tasks, and its impact on gray matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups, each comprising 10 animals. One control group learned discrimination tasks that were similar but lacked any reversal component, and the other control group engaged in no learning. Gray matter changes were prominent in posterior orbitofrontal cortex/anterior insula but were also found in three other frontal cortical regions: lateral orbitofrontal cortex (orbital part of area 12 [12o]), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest, and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison with controls. In a final set of experiments, we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.