Summary: Quitting smoking is often a biological battle between a hyperactive reward system and a weakened self-control center. A new clinical tria reveals that a noninvasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) can shift this balance.
By targeting the brain’s “control center,” researchers successfully reduced cigarette consumption by an average of 11 cigarettes per day—outperforming strategies aimed at suppressing cravings.
Key Research Findings
- Targeting Self-Control: Stimulating the dorsolateral prefrontal cortex (DLPFC)—the region responsible for restraint and decision-making—was the most effective strategy.
- The “Top-Down” Effect: Researchers found that enhancing the control system naturally regulates the reward system. Brain scans showed increased activity in the prefrontal cortex and a corresponding decrease in reward-related regions like the orbitofrontal cortex.
- Significant Reduction: Participants receiving DLPFC stimulation reduced their smoking by over 11 cigarettes per day, a result significantly higher than those in the placebo or reward-dampening groups.
- Biological Proof: The reduction in smoking was mirrored by lower self-reported cravings and reduced carbon monoxide levels, a key biological marker of tobacco use.
- Precision Medicine: The study used brain imaging to tailor magnetic pulses to each participant’s unique brain structure.
Source: Medical University of South Carolina
For many people who smoke, quitting is not just a matter of willpower. It is a tug-of-war in the brain – between the pull of reward and the ability to resist.
A new study published in the Journal of Psychiatric Research suggests that shifting that balance may be possible. Using a noninvasive brain stimulation technique called repetitive transcranial magnetic stimulation, or rTMS, researchers at MUSC Hollings Cancer Center found that stimulating a specific brain region that regulates self-control significantly reduced how much people smoked.
A brain-based approach to a stubborn problem
Cigarette smoking remains one of the leading causes of preventable death, yet quitting is notoriously difficult. Even with medication and counseling, fewer than 1 in 10 smokers achieve long-term success.
Part of the challenge is that addiction is not just behavioral – it is also biological.
“In addiction, brain systems can get out of balance,” explained lead researcher Xingbao Li, M.D., an associate professor in the MUSC Department of Psychiatry & Behavioral Sciences. “One system, tied to reward and craving, becomes overactive. Another, responsible for control and decision-making, becomes weaker.”
In this clinical trial, researchers tested how rTMS – which uses magnetic pulses to stimulate specific areas of the brain – could restore that balance.
They compared two approaches, each targeting a distinct brain circuit involved in smoking:
- Strengthening self-control by stimulating the dorsolateral prefrontal cortex (DLPFC), a brain region involved in decision-making and restraint.
- Dampening reward signals by stimulating the medial orbitofrontal cortex (mOFC), a brain region tied to craving and reward.
Participants – adult smokers motivated to quit – were randomly assigned to one of these groups or to receive a sham, placebo-like treatment. Each participant received 15 sessions of rTMS over three weeks, with brain imaging used to guide precisely where and how the stimulation was delivered.
“It’s a kind of precision medicine,” Li said. “We’re tailoring the treatment to each person’s brain.”
The approach builds on earlier MUSC research, exploring how brain imaging could be used to personalize rTMS for smoking cessation, helping to identify the most effective targets for each person.
Helping the brain to take back control
The difference between the approaches was striking.
Participants who received high-frequency stimulation to the DLPFC – the brain’s “self-control” region – reduced their cigarette use by an average of more than 11 cigarettes per day. That was a significantly greater reduction than in the reward-targeting or placebo conditions.
Stimulating the DLPFC also led to lower self-reported cravings and reduced carbon monoxide levels, which are biological markers of smoking. These effects persisted for at least a month after treatment. In contrast, the approach aimed at suppressing reward activity in the mOFC did not produce meaningful improvements in either of these areas.
Brain scans offered insight into why.
After treatment, participants in the DLPFC group showed:
- Increased activity in the prefrontal cortex, the brain’s control center.
- Decreased activity in reward-related regions, including the orbitofrontal cortex.
Importantly, the degree of these brain changes tracked with behavior: The greater the shift in brain activity, the more participants reduced their smoking.
Together, the findings suggest that helping the brain to regain control, as opposed to trying to suppress cravings, may be the more effective strategy for smoking cessation.
“It’s a top-down effect,” Li said. “You enhance the control system, and it naturally regulates the reward system.”
Why this matters for patients
The implications could be meaningful for people who struggle with existing treatments.
Some smokers cannot tolerate medications. Others relapse despite repeated attempts. And among patients with cancer, many continue to smoke even after a diagnosis, when quitting becomes more critical.
At Hollings, patients can already access support through the Tobacco Treatment Program, which offers counseling, medications and evidence-based tools for smoking cessation. The program connects patients with specialists who address both the physical addiction to nicotine and the behavioral habits and triggers that make quitting difficult.
rTMS could eventually complement these efforts by offering a brain-based approach – one that targets the underlying circuitry of addiction.
This study was relatively small, and it was not designed to measure quit rates definitively. Larger trials are already underway to confirm the findings and test longer treatment courses.
But this first phase serves an important purpose by identifying which strategy works best.
“We wanted to compare the approaches and pick a winner,” Li said. “Now we know which direction to take in future studies.”
That direction – strengthening the brain’s ability to say no to cigarettes – may offer a new way forward for people trying to quit smoking, especially when other options have fallen short.
Key Questions Answered:
A: It’s easier to empower the “police” (self-control) than it is to silence the “party” (cravings). When the DLPFC is strong, it naturally keeps the reward-seeking parts of the brain in check, making the urge to smoke easier to ignore.
A: No. rTMS is noninvasive and uses magnetic pulses, similar to an MRI, to stimulate neurons. It does not require anesthesia or cause the type of seizure associated with older forms of electroconvulsive therapy.
A: While rTMS is already FDA-approved for depression and some smoking cessation protocols, this specific “precision” method is still in larger clinical trials to confirm long-term quit rates. However, it offers a vital new path for smokers who cannot tolerate medication or have relapsed multiple times.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this brain stimulation and addiction research news
Author: Leslie Cantu
Source: Medical University of South Carolina
Contact: Leslie Cantu – Medical University of South Carolina
Image: The image is credited to Neuroscience News
Original Research: Open access.
“DLPFC rTMS is more effective than sham or orbitofrontal stimulation for smoking cessation and alters frontal brain activity: A double-blind, sham-controlled randomized clinical trial” by Xingbao Li, Kevin A. Caulfield, Matthew J. Carpenter, Viswanathan Ramakrishnan, Evan S. Herrmann, Morgan Dancy, and Mark S. George. Journal of Psychiatric Research
DOI:10.1016/j.jpsychires.2026.02.053
Abstract
DLPFC rTMS is more effective than sham or orbitofrontal stimulation for smoking cessation and alters frontal brain activity: A double-blind, sham-controlled randomized clinical trial
Objective
Repetitive transcranial magnetic stimulation (rTMS) shows promise for smoking cessation, but its neural mechanisms remain unclear. It is unknown whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity. This study aimed to address this gap by comparing excitatory and inhibitory rTMS targeting distinct cortical circuits implicated in tobacco use disorder (TUD).
Methods
In a double-blind, sham-controlled design, treatment-seeking individuals with TUD were randomized to 15 sessions of personalized, fMRI-guided, E-field–dosed rTMS: (1) sham rTMS, (2) excitatory 10 Hz rTMS over the left dorsolateral prefrontal cortex (L-DLPFC; 3000 pulses/session), or (3) inhibitory 1 Hz rTMS over the left medial orbitofrontal cortex (L-mOFC; 900 pulses/session). fMRI scans were conducted pre- and post- 15 sessions of rTMS. Primary outcomes were reductions in cigarettes per day (CPD) and changes in blood-oxygen-level–dependent (BOLD) activity.
Results
Thirty-five of 46 participants completed the study (sham = 9; 10 Hz L-DLPFC = 12; 1 Hz L-mOFC = 14). The 10 Hz L-DLPFC group showed a significantly greater CPD reduction than 1 Hz L-mOFC and sham (−11.14 vs. −4.92 and −6.43, respectively; p < 0.0001, partial η2 = 0.135). rTMS to the L-DLPFC also increased prefrontal activity and decreased orbitofrontal activity (p < 0.05), with the degrees of CPD reduction correlating with enhanced activation in L-DLPFC (p < 0.05).
Conclusions
Enhancing executive control via 10 Hz rTMS over the L-DLPFC was more effective for smoking reduction than suppressing reward circuitry with 1 Hz rTMS over the L-mOFC. Findings suggest that strengthening prefrontal regulation of reward processing is a key mechanism by which rTMS promotes smoking cessation.
Trial registration
clinicaltrials.gov Identifier: NCT 04903028.
