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Brain reactivity to nicotine cues mediates the link between resting-state connectivity and cue-induced craving in individuals who smoke or vape nicotine

Neuropsychopharmacology volume 50, pages 983–990 (2025)Cite this article

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Abstract

Individual differences in brain intrinsic functional connectivity (FC) and reactivity to nicotine cues are linked to variability in clinical outcomes in nicotine dependence. However, the relative contributions and potential interdependencies of these brain imaging-derived phenotypes in the context of craving and nicotine dependence are unclear. Moreover, it is unknown whether these relationships differ in individuals who smoke versus vape nicotine. To investigate these questions, eighty-six individuals who use nicotine daily (n = 67 smoking, n = 19 vaping) completed either a smoking or vaping cue-reactivity task and a resting-state scan during functional magnetic resonance imaging (fMRI). Validating the efficacy of the smoking and vaping tasks, both cohorts displayed robust reactivity to nicotine versus neutral cues in the default mode network (DMN) and the anterior insula (AI), a primary node of the salience network (SN), which did not habituate over time. In the smoking and vaping groups, lower prefrontal reactivity to nicotine versus neutral cues and greater resting-state FC between nodes of the SN and DMN were associated with higher cue-induced craving. Moreover, we found that the former partially mediated the latter, suggesting a mechanism in which high resting SN-DMN connectivity increases craving susceptibility partly via a constraining effect on regulatory prefrontal reactivity to cues. These relationships were not impacted by group, suggesting that links between brain function and craving are similar regardless of smoking or vaping nicotine.

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Fig. 1: Comparison of smoking and vaping groups on subjective ratings and brain reactivity to nicotine cue-reactivity task.
Fig. 2: Brain activation in insula and default mode network regions of interest over time.
Fig. 3: Brain correlates of cue-induced changes in subjective nicotine craving.
Fig. 4: Results of mediation analyses.

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Data availability

The datasets analyzed during the current study are available upon reasonable request.

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Funding

This research was supported by the National Institutes on Drug Abuse R01DA039135 and the Intramural Research Program of the NIH, NIDA.

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Authors and Affiliations

  1. National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA

    Laura Murray, Maria K. Scavnicky & Amy C. Janes

  2. McLean Hospital, Belmont, MA, USA

    Cole Korponay, Scott E. Lukas & Blaise B. Frederick

  3. Harvard Medical School, Boston, MA, USA

    Cole Korponay, Scott E. Lukas & Blaise B. Frederick

Authors
  1. Laura Murray
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  2. Maria K. Scavnicky
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  3. Cole Korponay
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  4. Scott E. Lukas
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  5. Blaise B. Frederick
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  6. Amy C. Janes
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Contributions

LM, BBF, SEL, CK, and ACJ contributed to the design and implementation of the research, to the analysis of the results, and to the writing of the manuscript. MKS contributed to the analysis of the results and to the writing of the manuscript

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Correspondence to Laura Murray.

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Murray, L., Scavnicky, M.K., Korponay, C. et al. Brain reactivity to nicotine cues mediates the link between resting-state connectivity and cue-induced craving in individuals who smoke or vape nicotine. Neuropsychopharmacol. 50, 983–990 (2025). https://doi.org/10.1038/s41386-025-02083-6

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