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Brain Site Appears to Play Key Role in Smokers' Addictive Behavior

A small group of patients who found it easy to quit smoking cigarettes after suffering a brain injury have led scientists to conclude that the insular cortex, or insula, plays a key role in reinforcing behavioral cues that foster maintenance of the addiction in smokers.

Researchers at the University of Iowa and the University of Southern California's Brain and Creativity Institute in Los Angeles studied 69 patients with brain damage who had been smokers previously, including 19 with damage to the insula, a silver-dollar-sized region deep within the cerebral cortex. Sixteen patients reported having little difficulty quitting cigarettes, with no subsequent urges to resume.

The study, which was published in Science (2007;315:531–534), highlighted the case of a 38-year-old man who gave up a two-pack-per-day cigarette habit without difficulty after a stroke-related injury to the insula.

“The man said his body ‘simply forgot' the urge to smoke,” said lead author Antoine Bechara, PhD, associate professor of psychology at the University of Southern California's Brain and Creativity Institute.

He told Neurology Today in a telephone interview that he and his colleagues reviewed a large database of brain injury patients at the University of Iowa, and identified those with similar injuries who had also quit smoking. They then contacted the patients, some of whom had not had a cigarette in 15 years, and questioned them about their experience quitting smoking.

“Many other patients shared the same common phenomenon. They quit just like a light switch had been turned off,” Dr. Bechara said. “When we went back and looked at brain imaging in these patients and compared their experience with ex-smokers with damage to other areas, the highest likelihood of interruption of addiction was related to damage to the insula. There were some exceptions, but the percentage was really high.”

For comparison, the insula patients were matched with 50 smokers with lesions to other areas with similar smoking histories. Few of these patients had been able to quit smoking without difficulty.

The criteria for “disruption of smoking addiction” included quitting less than one day after lesion onset without any resumption of smoking; rating the difficulty of quitting as less than three on a scale of seven; and feeling no urges to start again after quitting.

“Other brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking,” said Dr. Bechara. “No one was paying any attention to the insula. Most of the research in addiction was focused on the nucleus acumbens, which is involved in the sensation of pleasure, and the orbitofrontal cortex.”


The finding of the insulas role in addiction will open new directions for therapy development, investigators said.

The insula is located within the lateral sulcus, which separates the temporal lobe and inferior parietal cortex, and is associated with visceral functions and integrating somatosensory information and environmental cues, he explained. It receives information from other parts of the body and is thought to help translate those signals into something we subjectively feel, such as hunger, pain, or craving for a drug.

Because the patients reported losing the urge to smoke so suddenly and without difficulty or relapse, Dr. Bechara and his colleagues concluded that insula damage reduced the patients' actual urge to smoke rather than the pleasurable experience, or “reward,” associated with smoking.


Patients with other addictions were excluded from participating, however, Dr. Bechara said he believes the phenomenon can be “generalized” and may ultimately apply to alcohol abuse, overeating, and other addictions, especially risk-taking compulsive behaviors like gambling.


Dr. Antoine Bechara: “Other brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. No one was paying any attention to the insula.”

“Neuroimaging studies suggest the insula is involved in other types of craving, including cocaine and alcohol,” he said.

Because the insula is also involved in appetite, a follow-up survey was conducted. The researchers found that insula damage did not affect patients' desire to eat, however because eating is so vital for survival, multiple brain regions may serve as redundant back-up systems, he explained. Nonetheless, overeaters exhibit similar maintenance cues in their food addiction.

Imaging studies of the insula have shown that the region is activated by drug-associated cues, such as the sight of people doing drugs or drug paraphernalia. Arthur Brody, MD, associate professor in residence in the department of psychiatry and biobehavioral sciences at the University of California-Los Angeles, has studied the phenomenon in drug addicts.

“This is a unique study,” he told Neurology Today in a telephone interview. “Our group and some others have shown the insula may be involved with [drug] craving, so it's not surprising that damage appeared to eliminate the desire to smoke. I'm a little surprised that damage to just that one area resulted in the effect, however.”

Tobacco is right up there with opiates in terms of addiction, said Dr. Brody, who has treated more than 4,000 smokers in cessation programs. “The success rate is only around 38 percent, and that's with comprehensive treatment.”


Because the insula is too deep within the brain to be safely or easily targeted by any existing therapies, and because the insula may also reinforce healthy urges such as sex or appetite, developing any kind of targeted treatment for smokers may take years, Dr. Bechara told Neurology Today.

However, the finding of the insula's role in addiction will open new directions for therapies, including possible drugs targeted to the region, he said.

“There is a lot of potential for pharmacological developments.” Transcranial magnetic stimulation (TMS) offers perhaps the greatest potential as a therapy in the short term, he noted.

“Right now we can't get signals deep enough into the brain to reach the insula, but it is likely that this can be developed. What's even more important is that TMS only causes temporary dysfunction of the targeted area of the brain, so that side effects are minimal. Addiction is marked by changes in neural circuitry, and the insula is only part of that circuitry,” he said, adding: “We have a lot of questions and a lot of homework ahead of us, and we're hoping that other researchers will get involved.”


“It's a really tremendous paper, one that points us in a whole new direction,” said Steven Grant, PhD, chief of the Clinical Neuroscience Branch at the National Institute on Drug Abuse. “Basically this study has opened up a whole new avenue of research in addiction,” he told Neurology Today in a telephone interview.

There have been numerous imaging studies suggesting that the insula plays a role in drug abuse and craving, but it has not been an area of great interest until now, he commented.

“Now it's clear that it has a critical role, and it may even have a role that is causative. We have to be suitably cautious though. This is a small patient sample and there were some issues with data collection, but what it indicates is that we need to follow up on the findings aggressively.”

There may be other brain regions involved as well, he added. “We don't know how much redundancy there is in this part of the brain. We do know that there is a lot of literature showing the insula as critical in processing somatosensory visceral sensations, but we don't know what else is going on or how these capabilities are used for higher order processing.”

He noted that the finding fits in well with the theory of “sense-memory”— that anticipation of a somatosensory state helps guide decision-making on a very basic level.

“If you can get rid of sense-memory for something like smoking, it appears that you lose the desire for the drug, but that's speculation at this point.”


The insular cortex, or insula, seems to play a key role in reinforcing behavioral cues that foster maintenance of addiction in smokers.


• Naqvi NH, Ridrauf D, Damasio H, Bechara A. Damage to the Insula Disrupts Addiction to Cigarette Smoking. Science 2007;315:531–534.
• Brody A, Mandelkern M, London E, et al. Brain metabolic changes during cigarette craving. Arch Gen Psychiatry 2002;59:1162–1172.
• Grant, S, London, E, Newlin D, et al. Activation of memory circuits during cue-elicited cocaine craving. PNAS 1996;93:12040–12045.
    • London D, Ernst M, Grant S, Bonson K, Weinstein A. Orbitofrontal Cortex and Human Drug Abuse: Functional Imaging. Cereb Cortex 2000;10:334–342.