Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Feb;18(1):207-219.
doi: 10.1007/s11682-023-00820-3. Epub 2023 Nov 23.

Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial

Xingbao Li  1   2 , Kevin A Caulfield  3 , Karen J Hartwell  3   4 , Scott Henderson  5 , Kathleen T Brady  3   4 , Mark S George  3   5   4
Affiliations
Randomized Controlled Trial

Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial

Xingbao Li et al. Brain Imaging Behav. 2024 Feb.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving, decrease cigarette consumption, and increase the abstinence rate in tobacco use disorders (TUDs). We used functional magnetic resonance imaging (fMRI) to investigate the effect of 10 sessions of rTMS on cortical activity and neural networks in treatment-seeking smokers. Smoking cue exposure fMRI scans were acquired before and after the 10 sessions of active or sham rTMS (10 Hz, 3000 pulses per session) to the left dorsal lateral prefrontal cortex (DLPFC) in 42 treatment-seeking smokers (≥ 10 cigarettes per day). Brain activity and functional connectivity were compared before and after 10 sessions of rTMS. Ten sessions of rTMS significantly reduced the number of cigarettes consumed per day (62.93%) compared to sham treatment (39.43%) at the end of treatment (p = 0.027). fMRI results showed that the rTMS treatment increased brain activity in the dorsal anterior cingulate cortex (dACC) and DLPFC, but decreased brain activity in the bilateral medial orbitofrontal cortex (mOFC). The lower strength of dACC and mOFC connectivity was associated with quitting smoking (Wald score = 5.00, p = 0.025). The reduction of cigarette consumption significantly correlated with the increased brain activation in the dACC (r = 0.76, p = 0.0001). By increasing the brain activity in the dACC and prefrontal cortex and decreasing brain activity in the mOFC, 10 sessions of rTMS significantly reduced cigarette consumption and increased quit rate. Reduced drive-reward and executive control functional connectivity was associated with the smoking cessation effect from rTMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02401672.

Keywords: ACC; DLPFC; Executive control circuitry; Reward circuitry; Smoking cessation; TMS; Tobacco use disorder.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest/Competing interests The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Study design and fMRI paradigm. A. Timeline for treatment and functional MRI; B. Cigarette smoking cue-induced fMRI paradigm
Fig. 2
Fig. 2
Ten sessions of rTMS of 3000 pulses over the left DLPFC reduced brain activity in the medial orbital frontal cortex and increased brain activity in the prefrontal cortex. Whole-brain activation to smoking cue (smoking greater than neutral) across rTMS groups (sham vs. active) and treatment course (pre vs. post). Illustrated are axial MRI slices of a Montreal Neurological Institute (MNI) standard brain at pre-treatment and post-treatment. Cluster-level threshold was set at p < 0.05 using family-wise error (FWE) rate correction for multiple comparisons, with voxel-wise threshold p < 0.001. Pre_Sham: Baseline-MRI scan in Sham treatment. Pre_Active: Baseline-MRI scan in Active treatment group. Post_Sham: Post-MRI scan in Sham treatment group. Post_Active: Post-MRI scan in Active treatment
Fig. 3
Fig. 3
Reduced number of cigarettes smoked per day associated with increased brain activity in the dorsal anterior cingulate cortex (dACC). A. rTMS treatment effect correlated to the increased brain activity in dorsal ACC (p < 0.001, uncorrected, cluster size > 10 voxels). B. Correlation plot- increased beta value vs reduction of cigarettes per day. R = 0.76, p. < 0.001
Fig. 4
Fig. 4
Ten sessions of rTMS over the left dorsolateral prefrontal cortex (L-DLPFC) reduced the connection of DLPFC and dACC and increased the connection of mOFC and dACC. A. Regions of interest were included for network analysis on the left hemisphere. Averaged coordinates were rendered on the 3 D template brain. B. Comparison of beta coefficients on drive-reward and executive control circuits between active rTMS and sham treatments. Significant elevation in the connections between L-DLPFC–mOFC and L-DLPFC–dACC after the active rTMS treatment. Significant reduction in the connection of dACC–mOFC after the active treatment. The significant interaction of treatment groups and connections showed that the active rTMS treatment significantly modulated drive-reward and executive control connectivity compared to sham treatment (F1,5 = 3.30, p = 0.006). No significant effect of connectivity was found after sham treatment. * p-value < 0.017, ** p-value < 0.003
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Allenby C, Falcone M, Wileyto EP, Cao W, Bernardo L, Ashare RL, Janes A, Loughead J, & Lerman C (2020). Neural cue reactivity during acute abstinence predicts short-term smoking relapse. Addiction Biology, 25(2), e12733. - PMC - PubMed
    1. American Psychiatric Association 2013. Substance Abuse Disorder. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 10.1176/appi.books.9780890425596 - DOI
    1. Amiaz R, Levy D, Vainiger D, Grunhaus L, & Zangen A (2009). Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction, 104(4), 653–660. - PubMed
    1. Baleydier C, & Mauguiere F (1980). The duality of the cingulate gyrus in monkey. Neuroanatomical Study and Functional Hypothesis. Brain, 103(3), 525–554. - PubMed
    1. Brody AL, Mandelkern MA, Olmstead RE, Jou J, Tiongson E, Allen V, Scheibal D, London ED, Monterosso JR, Tiffany ST, Korb A, Gan JJ, & Cohen MS (2007). Neural substrates of resisting craving during cigarette cue exposure. Biological Psychiatry, 62(6), 642–651. - PMC - PubMed

Publication types

Associated data