Hannah Kazis-Taylor

A recent Yale study has revealed alterations in smokers’ brains that could provide a deeper understanding of the neurochemistry associated with addictive behaviors.

The researchers, who work in various departments at the School of Medicine including psychiatry, diagnostic radiology, internal medicine and the Child Study Center, used functional MRI to evaluate brain activity in smokers and nonsmokers. They found that smokers’ brains demonstrated different connectivity than nonsmokers’ when presented with imagery related to appetite, stress and relaxation. These findings show that smoking is associated with changes in neural functions, which could serve as targets for therapeutic intervention for addiction, according to the researchers.

“The pattern of connectivity during ‘favorite-food’ imagery again suggests that smokers are desensitized to food-related rewards in motivation and reward brain regions,” co-author and professor at the medical school Kathleen Garrison said. “This may be why smoking is associated with low body weight, and why you gain weight when you quit smoking.”

The inspiration for the current study came from an earlier study that revealed that smokers showed a lower response in the reward areas of the brain in response to drug-related cues, Garrison said. However, the current study did not examine individual brain regions, but instead analyzed the connections between them. Co-author and medical school professor Marc Potenza GRD ’93 MED ’94 said the researchers tried examining connectivity with this new “intrinsic connectivity distribution approach” because communication between brain regions is important for emotional and motivational feelings and behaviors.

Twenty-three smokers and 23 nonsmokers participated in the study. The researchers generated personalized, guided imagery scripts to be presented during an fMRI based on participants’ descriptions of their favorite foods, common relaxing experiences and recent personal stressful events.

Results showed that smokers exhibited greater connectivity between the supramarginal gyrus, which is located in the parietal lobe, and motivation-reward brain regions during favorite-food imagery exposure. According to Potenza, the supramarginal gyrus has been linked to somatosensory processes and connects to corticostriatal-limbic regions, which are implicated in motivational and emotional responses.

“Some of the regions that are involved in somatosensory processing are connecting differently to corticostriatal-limbic regions [in smokers],” Potenza said. “When exposed to food cues, it may in part explain why people have appetite differences when they’re smoking as compared to when they are not smoking.”

Garrison said the weight loss that comes with smoking, and is often reversed when one quits smoking, can cause people to have trouble with smoking cessation. Potenza said the weight gain involved in quitting must be considered for successful treatment.

Potenza also noted that he was struck by the connectivity differences for smokers in the “neutral-relaxing” condition. Smokers had greater connectivity between the precuneus, also part of the parietal lobe, and the posterior insula, which has been implicated

in cigarette cravings and awareness of one’s internal states. People often use substances to relax, so these differences in addicted individuals can have treatment implications, Potenza said.

“If we can help people to achieve [relaxation] without substances that are potentially harmful to them, like tobacco, then we can improve the health of these individuals,” Potenza said.

But the study does not show causation — that is, researchers did not conclude if the brain alterations are results of years of smoking or if they serve as a risk factor for smoking, Potenza said. He mentioned that some data suggest that even young children show brain differences that can be linked to substance use disorder in adulthood, but he said that longitudinal studies would be necessary to examine these data further.

Tony George, a former Yale psychiatry faculty member and current professor at the University of Toronto, called the current study “fine work.” However, he said he would be interested in finding out more about the brain alterations.

“The only question I have is whether these differences are truly due to smoking itself or a vulnerability for smoking,” George said. “Breaking down the non-smokers into former versus never smokers would differentiate between these possibilities.”

Garrison said that in the future, she would be interested to see if the brain differences found in smokers changed when they quit smoking. She wondered if the brain’s reward response to food would “recover” after cessation, which might lead to weight gain.

Further investigation may prove complicated because of all of the factors that play a part in addiction, Garrison said. She and Potenza agreed that there are many factors, both psychological and biological, that must be taken account in prevention and treatment.

“Addiction is a complex disease,” Garrison said. “There are changes related to the effects of nicotine, as well as changes related to genetics, development, experience and environment.”

According to the Centers for Disease Control and Prevention, cigarette smoking is the leading cause of preventable disease and death in the United States, accounting for more than 480,000 deaths every year.