India Herbs

Publication: San Francisco Chronicle

Author: Carl T. Hall

Date: January 26, 2007 

Smokers often feel it in their gut when they crave a cigarette. Now neuroscientists are offering a novel explanation that points to something between the ears: a deep-seated part of the brain known as the insula.

An unusual study of people with brain damage, caused in most cases by a stroke, suggests the compulsion to light up might be driven by the same little-studied brain region that helps us make sense of hunger pangs, nervous twitches and all sorts of visceral body signals.

Researchers said the findings identify an important new target for research into the biological underpinning of addiction, particularly into how people who try to quit a bad habit are vulnerable to relapse. It might even be possible to tamp down cravings, or at least monitor them more precisely, with therapies that target the insula, such as biofeedback training.

The insula, also known as the insular cortex, is found on either side of the head, nestled beneath the more familiar wrinkles of the outer neocortex. It previously has been linked to a wide array of functions, including emotion, pain, speech planning and movement. But it hasn’t been prominently cited before as a center of addiction circuits.

In the latest study, published in this week’s issue of the journal Science, researchers at the University of Southern California and University of Iowa found that longtime smokers who had sustained insula damage had a remarkably easy time giving up cigarettes.

One study subject said it was as if his body “forgot the urge to smoke.”

Lead author Antoine Bechara, an associate professor at USC’s Brain and Creativity Institute, likened smoking and other forms of addiction to a contest between the front part of the brain, the seat of rational decision-making, and an overactive insula generating cravings deeper down.

Beginning smokers initially might derive pleasure from tobacco, but longtime smokers who are trying to quit often say it’s not the longing for pleasure that keeps the habit going. Instead, a cigarette can seem the only way to satisfy a biological need to feel “normal.”

In those cases, Bechara said, “it turns out it’s the insula that is the culprit,” as evidenced by striking relief from nicotine cravings experienced by his insula-damaged study subjects.

Other brain regions, particularly those involved in memory and reward, are clearly involved in any learned habit like cigarette smoking. The insula ties in with those systems and could be a key part of the pathway that sets people up for relapse should they try to quit.

Researchers hope that it might also serve as a kind of “fuse” — a way to switch off the vicious cycle of late-stage addiction, craving and relapse.

“Addiction is acquired and maintained by a neural circuity — it involves a lot of parts of the brain,” Bechara said. “The question is whether you can disrupt that circuity if you knock out one critical area.”

The year-old brain institute at USC is directed by the husband-and-wife team of Antonio and Hanna Damasio, who until 2005 were based at the University of Iowa. The Damasios are prominent for their research into the physical origins of consciousness and emotion, including the role of the insula in those realms. Hanna Damasio was a senior author of the new study, led by a University of Iowa graduate student, Nasir Naqvi.

The study was partly financed by the National Institute on Drug Abuse, a part of the National Institutes of Health. Dr. Nora Volkow, the institute’s director, said the findings open important new leads for addiction treatment as well as basic research.

“It’s a fascinating study,” she said, suggesting that biofeedback or other techniques might be tried to “teach people to decrease activity of the insula,” or at least monitor craving impulses.

Neuroscientist Darwin Berg, a biology professor at UC San Diego, said the findings shift the focus of addiction research away from the brain’s reward pathways, opening a new way of thinking about brain function as it relates to addiction.

“All along we’ve know that addiction has this terrible inclination for relapse behavior,” he said. “What is exciting about this work is it focuses on a new region of the brain … that involves conscious awareness of bodily states, how you’re feeling, what’s going on in your body. So it’s a very interesting connection here.”

The findings draw new attention to the low-profile insular cortex, which serves as a kind of “brain within the brain,” said Dr. William Seeley, a clinical instructor in neurology at UCSF who has studied the insula in brain-damaged patients.

He said the findings were consistent with earlier evidence about the main functions of the insula.

“It has connections with every other part of the brain,” he said. “It’s the link between the emotions and your visceral state. Craving is a sort of visceral state — deep down in your gut you really need that cigarette, and you feel it in your body.”

Henry Lester, a senior scientist and brain researcher at the California Institute of Technology, said the study underscores the role of fundamental neurobiology in “any process that occurs in a person’s brain, no matter how complex or diffuse.”

“This study’s importance derives from its success at a scientific approach to the so-called ‘psychological’ reasons that nicotine addicts smoke,” he said by e-mail. “Nicotine addiction has many components, and it must be described at the level of individual molecules, of nerve cells, and of circuits of nerve cells.”

The new study looked at only 19 longtime smokers who had insular damage, six with damage on the right side, 13 with damage on the left. All of them had been smoking more than five cigarettes a day for at least two years before their strokes.

Those smokers were compared with 50 other smokers who had damage to other parts of the brain but not their insula. All of the study subjects were questioned to find out if they had quit, how soon afterward the brain damage occurred and whether they had relapsed or had strong cravings to resume the habit.

Thirteen of the 19 insula-damaged people had quit smoking, and all but one reported having quit easily and immediately after the brain damage. The likelihood of such a “disruption of smoking addiction” was strikingly less among the stroke patients who had damage elsewhere in the brain.

A larger study involving more patients could find different results. Still, the findings made public Thursday came as no surprise to some family members of people who had had strokes and suddenly gave up smoking.

Kate Thompson, a gallery manager in San Francisco, recalled how her late aunt and uncle, Bob and Fern Applegate of North Platte, Neb., had both been smokers most of their lives, until he developed emphysema and had to quit.

The aunt continued puffing away, even around her husband, until she had a stroke and instantly “lost the urge to smoke,” Thompson said.

Both of them died a few years ago. But Thompson said she is convinced the stroke eliminated the secondhand smoke risk and thus prolonged her uncle’s life.

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