New findings on the neurobiological basis of nicotine addiction may explain why 80 percent of smokers relapse after trying to quit.

Along with cocaine and methamphetamine, nicotine is one of the most dangerously addictive drugs — addicting as many as 45 percent of those who smoke on a regular basis. Many smokers trying to quit report an overwhelming desire to maintain the habit, an internal battle of wills science has not fully understood.

Now, scientists using brain-imaging technology say smokers suffering from nicotine withdrawal may experience trouble shifting from our brain’s default mode — introspective or self-referential — to the higher focus of the executive control network, which helps control cravings for drugs, foods, and other substances.

Like a jerky transmission in an old truck, the nicotine-addled brain has trouble shifting focus, says Caryn Lerman, a University of Pennsylvania researcher who led the study.

“What we believe this means is that smokers who just quit have a more difficult time shifting gears from inward thoughts about how they feel to an outward focus on the tasks at hand,” Lerman said in a statement. “It’s very important for people who are trying to quit to be able to maintain activity within the control network— to be able to shift from thinking about yourself and your inner state to focus on your more immediate goals and plan.”

In the study, smokers abstaining from tobacco experienced weakened connectivity between large neurological networks in the brain, including the default mode, executive control, and something called the salience network. Lerman and her colleagues believe this weakening of connectivity harms the brain’s ability to muster the will to quit smoking.

Though researchers had previously examined the effects of the drug on brain activity while in a resting mode, this new study is the first to look at the effects of smoking while the brain is in action. Thirty-seven healthy smokers ranging in age from 19 to 61 underwent two fMRI scans, measuring brain activity during abstinence and smoking as usual. Smokers in the study consumed at least a half-pack of cigarettes a day, or more.

Those scans revealed weakened connections between the default mode and salience network, which researchers found associated with increased urges to smoke, lowered mood, and other common symptoms of nicotine withdrawal.

“Symptoms of withdrawal are related to changes in smokers’ brains, as they adjust to being off of nicotine, and this study validates those experiences as having a biological basis,” Lerman said. “The next step will be to identify in advance those smokers who will have more difficulty quitting and target more intensive treatments, based on brain activity and network connectivity.”

In future visits to the doctor, patients wishing to quit smoking may be offered diagnostic tests to determine the best course of treatment, the researchers hope. Today, more than 16 million Americans suffer from at least one disease caused by smoking, including cancer, heart disease, stroke, diabetes, and various lung diseases.

Smoking costs the United States some $289 billion per year, including $133 billion in direct medical costs associated with smoking-related diseases, according to the Centers for Disease Control and Prevention. Through smoking and second-hand smoke, more than a half-million Americans die every year.

Source: Lerman C., Louhed, James, Ruparel, Kosha, Yang, Yihong, Stein, Elliot A. Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence Effects On Craving And Cognitive Function. JAMA Psychiatry. 2014.