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Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets
Open accessAbstract
The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control.
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“However, while both insula and dACC are components of the SN, they subserve different functions, with insula more related to internal somatic function and monitoring task performance (Eckert et al. 2009;Menon and Uddin 2010;Cai et al. 2014), while the dACC is”
From Brain Activity and Functional Connectivity Associated with Hypnosis (2016) · cites this paper as Cai et al. 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“the insula is involved in the processing of body control and experience, emotion, empathy, and time through its extensive connections to cortical and subcortical limbic structures (Menon and Uddin 2010;Cai et al. 2014).”
From Brain Activity and Functional Connectivity Associated with Hypnosis (2016) · cites this paper as Cai et al. 2014
Experimental — accuracy not yet measuredIn the citing paper
“The right anterior insula has been proposed to represent a hub that controls brain activity across different tasks and stimulus modalities to initiate and adjust cognitive control mechanisms (Cai et al. 2014).”
From Large-scale functional neural network correlates of response inhibition: an fMRI meta-analysis (2017) · cites this paper as Cai et al. 2014
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Cites
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Dissociable intrinsic connectivity networks for salience processing and executive control
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Self-citationHow do you feel — now? The anterior insula and human awareness
(Bud) Craig, A. D. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2555 · Cited by 6,657 · cited 2×
“…anterior– dorsal cognitive subdivision of the insula as opposed to its anterior– ventral and posterior subdivisions, which have been implicated in arousal, affective, and interoceptive processes (Critchley et al., 2005; Craig, 2009; Menon and Uddin, 2010; Cocchi et al., 2012; Chang et al., 2013).”
BackgroundSaliency, switching, attention and control: a network model of insula function
Menon, V., & Uddin, L. Q. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0262-0 · Cited by 5,592
Self-citationCorrespondence of the brain's functional architecture during activation and rest
Smith, S. M., Fox, P. T., Miller, K. L., Glahn, D. C., Fox, P. M., Mackay, C. E., Filippini, N., Watkins, K. E., Toro, R., Laird, A. R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905267106 · Cited by 5,150
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Self-citationSridharan, D., Levitin, D. J., & Menon, V. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800005105 · Cited by 2,892
Self-citationDistinct brain networks for adaptive and stable task control in humans
Dosenbach, N. U. F., Fair, D. A., Miezin, F. M., Cohen, A. L., Wenger, K. K., Dosenbach, R. A. T., Fox, M. D., Snyder, A. Z., Vincent, J. L., Raichle, M. E., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704320104 · Cited by 2,632
Inhibition and the right inferior frontal cortex: one decade on
Aron, A. R., Robbins, T. W., & Poldrack, R. A. (2014) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.12.003 · Cited by 2,166
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The role of prefrontal cortex in cognitive control and executive function
Friedman, N. P., & Robbins, T. W. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01132-0 · Cited by 1,737
“A possible solution of the issue may depend on sophisticated network analyses [99].”
BackgroundDemystifying cognitive flexibility: Implications for clinical and developmental neuroscience
Dajani, D. R., & Uddin, L. Q. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.07.003 · Cited by 1,046
The role of PFC networks in cognitive control and executive function
Menon, V., & D’Esposito, M. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01152-w · Cited by 654
Self-citationFractionating impulsivity: neuropsychiatric implications
Dalley, J. W., & Robbins, T. W. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.8 · Cited by 607
Distinct Global Brain Dynamics and Spatiotemporal Organization of the Salience Network
Chen, T., Cai, W., Ryali, S., Supekar, K., & Menon, V. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002469 · Cited by 480
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Metadata
- Authors
- Cai, W., Ryali, S., Chen, T., Li, C.-S. R., & Menon, V.
- Affiliations
- Stanford University (US)
- Yale University (US)
- Stanford Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-10-29
- Volume
- 34
- Issue
- 44
- Pages
- 14652-14667
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4212065
- OpenAlex
- W2060881658
- Cited by
- 362
- References
- 63
- Citations by year
- 2026: 10 · 2025: 30 · 2024: 56 · 2023: 24 · 2022: 35 · 2021: 34 · 2020: 40 · 2019: 25 · 2018: 24 · 2017: 29 · 2016: 32 · 2015: 21 · 2014: 1
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA021449, R01AA021449)
- National Institute on Drug Abuse (DA026990, DA023248, R01DA023248, K02DA026990)
- National Institute of Neurological Disorders and Stroke (RF1NS086085, NS071221, R21NS071221, NS086085, R01NS086085)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K25HD074652)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
- Keywords
- inhibitory control, right inferior frontal cortex, right anterior insula, stop-signal task, functional parcellation, intrinsic brain activity, functional connectivity, anterior cingulate cortex, dorsomedial prefrontal cortex, individual differences, saliency detection
- MeSH terms
- Brain Mapping, Cerebral Cortex, Female, Frontal Lobe, Humans, Inhibition, Psychological, Magnetic Resonance Imaging, Male, Models, Neurological, Nerve Net, Neuropsychological Tests, Psychomotor Performance, Reaction Time, Executive Function
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