A brain-based approach may improve smoking cessation treatment success

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 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 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."

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.

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.

Source:

Medical University of South Carolina

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