Insula demonstrates a non-linear response to varying demand for cognitive control and weaker resting connectivity with the executive control network in smokers
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Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.
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Decreased rsFC between the right aIC and right superior frontal gyrus has been reported in smokers.
“For instance, decreased rsFC between the right aIC (component of the SN) and right superior frontal gyrus (component of the ECN) has been reported in smokers (Fedota et al., 2016).”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Fedota et al., 2016
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Time varying connectivity across the brain changes as a function of nicotine abstinence statePreprint
Fedota, J. R., Ross, T. J., Castillo, J., McKenna, M. R., Matous, A. L., Salmeron, B. J., Menon, V., & Stein, E. A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.25.917617
Self-citationThe structural and functional changes of the insula in people with addiction
He, X., & He, Q. (2021) · Advances in Psychological Science · doi:10.3724/sp.j.1042.2021.01438
Old Protein, New Medicine - Brain-Derived Neurotrophic Factor [Working Title]
Erbaş, O., & Altuntaş, İ. (2023) · Biochemistry · doi:10.5772/intechopen.111201
Dynamic Brain Network Changes Associated with Successful Smoking CessationPreprint
Im, J. J., Kim, H., Lee, J.-H., Park, H. J., Joh, H., & Ahn, W. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.13.676003
Longitudinal brain connectivity changes associated with successful smoking cessation
Im, J. J., Kim, H., Lee, J.-H., Park, H. J., Joh, H., & Ahn, W. (2025) · Frontiers in Psychology · doi:10.3389/fpsyg.2025.1734803
Xu, H., Liu, X., Yang, H., Pan, P., Gu, S.-Y., Li, W.-H., & Wang, S. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1762620
- Authors
- Fedota, J. R., Matous, A. L., Salmeron, B. J., Gu, H., Ross, T. J., & Stein, E. A.
- Affiliations
- National Institute on Drug Abuse (US)
- Corresponding author
- Fedota, John R
- Venue
- Neuropsychopharmacology
- Published
- 2016-04-26
- Volume
- 41
- Issue
- 10
- Pages
- 2557-2565
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4987854
- OpenAlex
- W2342434642
- Cited by
- 45
- References
- 53
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 2 · 2017: 7 · 2016: 3
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99 DA999999)
- National Institute on Drug Abuse (NDA13001-001-00000)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- cognitive control, nicotine dependence, smoking, insula, frontoparietal network, flanker task, resting-state functional connectivity, superior frontal gyrus, salience attribution
- MeSH terms
- Adolescent, Adult, Brain, Cognition Disorders, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Oxygen, Reaction Time, Smoking, Young Adult, Executive Function
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