The role of the orbitofrontal cortex in smoking cue-reactivity in onset phase of smoking behavior, a fMRI study in adolescents.

Overview

1. Radboud University Medical Center, Department of Psychiatry, 6500 HB, Nijmegen, The Netherlands
2. Donders Institute, Donders Center of Medical Neurosciences, 6525 EN, Nijmegen, The Netherlands/Radboud University Medical Center, Department of Medical Neuroscience, Nijmegen, The Netherlands
3. Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), 6500 HE, Nijmegen, The Netherlands
4. Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, 1105 AZ, Amsterdam, The Netherlands
5. Radboud University Medical Center, Department of Medical Imaging, 6500 HB, Nijmegen, The Netherlands
6. GGD Noord- en Oost Gelderland, Warnsveld, 7231 AC, The Netherlands
7. Behavioural Science Institute, Radboud University, Nijmegen, 6525 XZ, The Netherlands

Abstract

Introduction: Adults with tobacco use disorder show increased activity patterns in frontostriatal regions compared to non-smokers when viewing smoking-related cues. Smoking mostly starts during adolescence. It is important to examine the development of smoking cue-reactivity patterns during early phases of tobacco use, specifically in adolescents who have not yet developed habitual smoking.

Methods: We tested in adolescents whether regular (n = 32) and experimental (n = 54) smoking adolescents differed from controls (n = 47) during an active smoking cue-reactivity task, through functional magnetic resonance imaging (MRI) with a whole brain and region of interest (ROI) approach (orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, middle frontal gyrus and striatum). Additionally, we investigated the association between smoking cue-related activity in significant ROIs and levels of pleasure of smoking and habitual smoking among all smoking adolescents.

Results: Whole-brain analyses showed no differences in smoking cue-reactivity between the groups. Region of interest analyses showed a higher smoking cue-related activity in the left OFC in regular smoking adolescents compared to controls. We found no dose–response relationships between smoking cue-related activity in the OFC and pleasure of smoking or habitual smoking.

Conclusions: Overall, we only observed increased smoking cue-related brain activity in the left OFC in regular smoking adolescents compared to non-smokers in the ROI analyses. These results suggest that OFC reactivity to smoking cues could be one of the first signs of the development of tobacco use disorder.

Implications: The understanding of the neurobiological development of smoking behavior and tobacco use disorder fosters optimal prevention and intervention strategies. Our data show altered neurobiological responses in the orbitofrontal cortex to smoking cues in non-addicted weekly smoking adolescents, suggesting that orbitofrontal cortex reactivity could be one of the first signs of tobacco use disorder development.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data availability

The meta data underlying this article are available at OSF via https://osf.io/6jw9p/.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 5 keywords, 10 MeSH terms, 3 funders, 48 references.

Cite

This paper

Tesselaar, D. R. M., Schellekens, A. F. A., Homberg, J. R., Booij, J., Guerrin, C. G. J., Dieleman, J., & Luijten, M. (2026). The role of the orbitofrontal cortex in smoking cue-reactivity in onset phase of smoking behavior, a fMRI study in adolescents. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 28(7), 1238-1246. https://doi.org/10.1093/ntr/ntag045

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