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Bold Prediction

Brain circuit that supports smoking cessation identified

by Sver Aune

Dr. Brett Froeliger

Dr. Brett Froeliger

Quitting smoking is hard. Yet success is more likely with strong communication between parts of the brain that inhibit automated behavior, according to a two-part study by Brett E. Froeliger, Ph.D., an addiction scientist in the Department of Neuroscience and a member of the MUSC Hollings Cancer Center. Froeliger and his colleagues published their results in the March 1, 2017 issue of JAMA Psychiatry.

Smoking becomes an automated behavior over time. In the brain, the urge to smoke begins the same way your foot automatically moves to the gas pedal when a red stoplight turns green. “A pack-a-day smoker places a cigarette in their mouth a few hundred times a day over years,” says Froeliger. “It becomes automated.”

This kind of automated physical behavior is stopped by a pathway in the brain called the inhibitory control network, which includes the prefrontal cortex and the thalamus. Communication through this pathway is often disrupted in the brains of smokers.

The work began when Froeliger was a postdoctoral researcher in the laboratory of Joseph F. McClernon, Ph.D., at Duke University. Froeliger and McClernon wanted to know if this pathway was involved when smokers attempted to quit. The laboratory examined inhibitory control networks in the brains of 81 nicotine-dependent adults committed to trying a 10-week smoking cessation program.

Before the program started, the researchers used functional MRI to monitor blood oxygenation level-dependent (BOLD) responses in the inhibitory control network. The patients were instructed to strike a computer key each time a colored circle appeared on screen, except on the rare occasion when a circle of a certain color appeared. A higher BOLD response meant that the brain was using more resources to inhibit the automated response of striking the key when the rare circle appeared.

After ten weeks, about half of the smokers had quit successfully. Intriguingly, it turned out that they had lower BOLD responses in their inhibitory control networks before trying to quit. In particular, BOLD responses were lower in the right thalamus and in the right inferior frontal gyrus, which sends a signal through the prefrontal cortex to the thalamus. They also had stronger functional connections between those regions. Patients who relapsed had scored just as well on the task as those who quit successfully. It seemed that their automated behavior may have required more effort to inhibit.

Froeliger continued the work with a new twist when he became faculty at MUSC. He wondered if the same thing happened to smokers who had not committed to quitting. The group measured BOLD responses in 26 smokers performing the same task. This time, however, the smokers were then presented with an open pack of their preferred brand of cigarettes, a lighter and an ashtray. They were paid one dollar for every six minutes they did not smoke, up to an hour. The idea was to give each one a small incentive to resist the temptation to smoke.

Similar to the first finding, the lower a person’s BOLD response, the longer the person resisted smoking. Those who resisted temptation longer also had stronger functional connections in their inhibitory control networks. This study is the first to link the strength of communication in a brain circuit that inhibits automated behavior with the ability to resist smoking. Therapies that support this pathway could help certain smokers who are trying to quit. “This work helps scientists understand why some smokers have a harder time quitting,” says Froeliger.