American Scientist

It's pretty obvious that choosing to smoke is a poor decision, considering how much is known about its adverse health effects. But the fact that addicts pursue their habits, even in light of an understanding of the potential rewards of stopping, has long been a topic of research in the neurology of addiction.

"Humans can use abstract ideas to veto their biological instincts. You can go on a hunger strike until literally you die in pursuit of an idea. There's no other animal on the planet that can do that," explains Read Montague, a neuroscientist at the Baylor College of Medicine in Houston. Addicts seem to lose some of this capacity, he says: "What it means to be an addict is that consequences that might happen in the future—good things that you may forgo, or bad things that you may not be able to avoid—can no longer stop you from chasing your habit."

Montague has demonstrated that people learn and make value judgments based not only on what they have experienced (called an experiential signal), but also on understanding what they might have gained if they had made other choices (called a fictive signal). Seeing the difference between both an expected outcome and an actual one is called an experiential error, whereas that for an actual outcome versus a better one that might have been possible is called a fictive error. Both of these signals change the activity of dopamine-activated neurons in the brain. Could it be that this change doesn't happen in addicts? Is it that chronic smokers don't experience these nervous system changes, or do such signals just not influence their behavior and choices?

Montague, along with his colleagues Pearl H. Chiu and Terry M. Lohrenz, decided to explore this question. "We're interested in the general process by which addiction hijacks learning mechanisms in your brain," he says, "and smoking is a gateway drug for lots of other things." The research group tested both chronic smokers and nonsmokers on a mock stock-market investment game. Smokers performed the trial twice, once deprived of nicotine and again when fully sated. During the test, participants underwent functional magnetic-resonance imaging (fMRI) to record changes in blood flow in their brains, a measure of neuronal activity.

The participants were each allotted $100 to invest in a model stock market, so the participants stood to make real financial gains from their activities. There were 20 investment rounds, and after each step the participants were shown the fluctuation in the market, how much their allotment had changed and the maximum amount they could have gained by investing a different amount. At the end of the trial, participants left with the actual amount of funds they had won—an average of $120. ("Somebody walked out with $400," notes Montague.)

The investigators focused on data from rounds where participants gained money in the market. They found that it was possible to predict how nonsmokers would alter their investment behavior in the next step, based on how much more they could have gained in the previous round had they allotted their funds differently. "It accounts for 60 percent of the variance in nonsmokers' next choice," Montague says. "In smokers, whether sated or not, it had no influence whatsoever, none."

"Say you bet 40 percent of your $100, and then the market fluctuates. When it goes up, every bet bigger than 40 percent would have made more money. That drives nonsmokers to really increase their bet next time. But in smokers, it has no impact on what they do next; they are only driven by their actual gains," Montague says. Smokers are only influenced by rewards they directly experience as the result of an action they have taken. They choose smaller, more immediate outcomes over those that are larger but more delayed.

However, nonsmokers and both sated and nicotine-deprived smokers all had the same neural response on the fMRI scan to the revelation of the largest possible investment return. Thus it appears that smokers' brains do in fact compute and understand that a different outcome might have been possible, but this does not translate into a control signal that affects their next behavioral choice.

"Another interesting case is, suppose you put in a lot, say 85 percent, and the market fluctuates positively, so now you've won a whole lot. You couldn't have won that much more, just 15 percent in this case. People back down from big wins like that, and there's never been a good explanation for why. We didn't see that effect at all in the smokers." Montague thinks this research may provide an underlying neurological explanation for this phenomenon: There wasn't a big enough fictive-error signal from the experience for nonsmoking participants to decide they should be risking as much in the next round.

Montague plans to tease out more details by next studying a large group of adolescents, before any have started smoking, over a number of years. Such quantitative results may make it possible for him to develop a risk index for addiction. His work could also be a step toward deciphering any biological explanation, such as an anomalous number of dopamine receptors, that may underlie the breakdown of this behavioral pathway, and help in determining whether there's any chemical way to restore the process.

So, are people with impaired control signals more likely to take up smoking, or does smoking itself somehow interrupt this neural behavioral-response pathway? Montague's working hypothesis is that it's both: Some people may be predisposed to a weakly coupled behavioral response to the neural signal, but smoking further breaks down the pathway.

"I think that it's tending to select people for whom this is already a weak coupling," he says. "Because in a sense, if you've got a really strong capacity to use what might happen to you tomorrow to put a drink or a cigarette down, it's just going to be harder to get you addicted."