Smoking Cessation Induced by Deep Repetitive Transcranial Magnetic Stimulation of the Prefrontal and Insular Cortices: A Prospective, Randomized Controlled Trial
Open accessAbstract
Background Tobacco smoking is the leading cause of preventable death in developed countries. Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex (PFC) can cause lasting reductions in drug craving and consumption. We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation (TMS) of the PFC and insula bilaterally can induce smoking cessation.Methods Adults (N = 115) who smoke at least 20 cigarettes/day and failed previous treatments were recruited from the general population. Participants were randomized to receive 13 daily sessions of high-frequency, low-frequency or sham stimulation following, or without, presentation of smoking cues. Deep TMS was administered using an H-coil version targeting the lateral PFC and insula bilaterally. Cigarette consumption was evaluated during the treatment by measuring cotinine levels in urine samples and recording participants' self-reports as a primary outcome variable. Dependence and craving were assessed using standardized questionnaires.Results High (but not low) frequency deep TMS treatment significantly reduced cigarette consumption and nicotine dependence. The combination of this treatment with exposure to smoking cues enhanced reduction in cigarette consumption leading to an abstinence rate of 44% at the end of the treatment and an estimated 33% 6 months following the treatment.Conclusions This study further implicates the lateral PFC and insula in nicotine addiction and suggests the use of deep high-frequency TMS of these regions following presentation of smoking cues as a promising treatment strategy.
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Clinical trials have shown that H-coil TMS of the insula alleviated symptoms in substance use disorders.
“clinical trials have shown that H-coil TMS of the insula in substance use disorders alleviated symptoms [118].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [118]
In that trial, cigarette consumption and nicotine dependence decreased, with the largest effects in those exposed to smoking cues.
“There was reduced cigarette consumption and nicotine dependence, and the effects were greatest in the individuals that were exposed to smoking cues [46].”
The largest addiction TMS study to date, by Dinur-Klein et al. 2014, found that left DLPFC TMS reduced cigarette consumption for 3 months.
“the largest TMS study in addiction to date was performed by Dinur-Klein and colleagues (2014) [46] wherein they demonstrated that TMS delivered to the left DLPFC reduced cigarette consumption for 3 months.”
In a prospective double-blind sham-controlled study, 115 regular cigarette smokers were randomized to 10 daily TMS treatments, with half shown visual smoking cues before each session.
“In this prospective, double-blind, sham-controlled study, 115 regular cigarette smokers were randomized to receive 10 daily treatments of TMS. Immediately before each session, half of the participants were presented with visual smoking cues.”
In smokers (n = 115), high-frequency deep TMS (10 Hz) to the lateral PFC and insula bilaterally significantly reduced cigarette consumption, as well as nicotine dependence.
“High-frequency deep TMS (10 Hz) was found to significantly reduce cigarette consumption, as well as nicotine dependence.”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Dinur-Klein et al., 2014
No studies have yet to investigate brain stimulation of the insula in addiction, with the exception of one clinical trial in smokers that targeted the insula and PFC together.
“No studies have yet to investigate brain stimulation of the insula in addiction, with the exception of one clinical trial in smokers that targeted the insula and PFC together (Dinur-Klein et al., 2014).”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Dinur-Klein et al., 2014
Studies targeting the insula are lacking as there is currently only one study completed thus far.
“Studies targeting the insula are lacking as there is currently only one study completed thus far (Dinur-Klein et al., 2014).”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Dinur-Klein et al., 2014
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- Authors
- Dinur-Klein, L., Dannon, P., Hadar, A., Rosenberg, O., Roth, Y., Kotler, M., & Zangen, A.
- Affiliations
- Tel Aviv University (IL)
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Zangen, Abraham
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 76
- Issue
- 9
- Pages
- 742-749
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2056417054
- Cited by
- 367
- References
- 51
- Citations by year
- 2026: 27 · 2025: 37 · 2024: 44 · 2023: 53 · 2022: 32 · 2021: 34 · 2020: 24 · 2019: 29 · 2018: 26 · 2017: 19 · 2016: 20 · 2015: 18 · 2014: 4
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Keywords
- smoking cessation, nicotine dependence, nicotine craving, cue exposure, dorsal prefrontal cortex, insula, high-frequency stimulation, low-frequency stimulation, H-coil
- MeSH terms
- Adult, Analysis of Variance, Biophysics, Cerebral Cortex, Cotinine, Creatinine, Cues, Double-Blind Method, Female, Humans, Male, Middle Aged, Prospective Studies, Surveys and Questionnaires, Smoking, Smoking Cessation, Prefrontal Cortex, Transcranial Magnetic Stimulation, Self Report
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