They were cigarette smokers. Then a stroke overcame his addiction.

Scanning an injured brain often produces a map of unrecoverable losses, revealing points where the damage causes memory difficulties or tremors.

But in rare cases, these scans can expose just the opposite: graphs of brain regions where an injury miraculously alleviates someone’s symptoms, offering clues to how doctors can do the same.

A team of researchers has now taken a fresh look at a set of such brain images, taken of nicotine-addicted smokers, in which strokes or other injuries helped them to spontaneously quit smoking. The results, the scientists said, showed a network of interconnected brain regions that they believe underlie addiction-related disorders that potentially affect tens of millions of Americans.

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An undated illustration provided by Joutsa, Fox et al., Nature Medicine 2022 shows brain injuries associated with addiction remission, in red. (Joutsa, Fox et al., Nature Medicine 2022 via The New York Times)

The study, published in the journal Nature Medicine on Monday, supports an idea that has gained traction recently: that addiction does not live in one region of the brain or another, but in a circuit of regions linked by threadlike nerve fibers.

The results may provide a clearer set of targets for addiction treatments that deliver electrical pulses to the brain, new techniques that have shown promise in helping people quit smoking.

“One of the biggest problems with addiction is that we don’t really know where in the brain the main problem that we should target with treatment is,” said Dr. Juho Joutsa, one of the study’s lead authors and a neurologist at the University. from Turku in Finland. “Hopefully, after that, we’ll have a very good idea of ​​these regions and networks.”

Research over the past two decades has solidified the idea that addiction is a disease of the brain. But many people still believe that addiction is voluntary.

Some independent experts said the latest study was an extraordinarily powerful demonstration of the brain’s role in substance use disorders. Among smokers who had strokes or other brain injuries, those with damage to a particular neural network experienced immediate relief from their cravings.

The researchers replicated their findings in a separate group of brain-injured patients who completed an alcoholism risk assessment. The brain network associated with a lower risk of alcohol dependence was similar to the one that facilitated nicotine dependence, suggesting that the circuit may underlie a broader set of addictions.

“I think this could be one of the most influential publications not just of the year, but of the decade,” said A. Thomas McLellan, professor emeritus of psychiatry at the University of Pennsylvania and former deputy director of the Office of National Drug Control Policy, who did not participate in the study. “This dispels many of the stereotypes that still pervade the addiction field: that addiction is bad parenting; addiction is a weak personality; vice is a lack of morality.”

In recent years, a succession of studies have identified specific brain regions where an injury, or injury, appeared to be associated with addiction relief. But the targets kept changing.

“People have not been successful in showing consistency in the areas involved,” said Dr. Hamed Ekhtiari, an addiction treatment specialist at the Laureate Institute for Brain Research in Tulsa, Oklahoma.

In the new study, Joutsa applied sophisticated statistical techniques to an old set of brain scans of Iowa smokers who had suffered neural damage. An earlier analysis of the same scans suggested that patients with damage to the insula, a region of the brain involved in conscious impulses, were more likely to quit smoking.

But Joutsa, going back to the same pixel-by-pixel scans, noticed that many patients without insula lesions also lost the urge to smoke. “There was something about the story of the insula, but it wasn’t the whole story,” he said.

Working with Dr. Michael Fox, an associate professor of neurology at Harvard Medical School, Joutsa examined a second set of scans from smokers who had suffered strokes in Rochester, New York. In all, they analyzed 129 cases.

The team struggled to find individual brain regions where the lesions would help patients quit smoking. Instead, the researchers turned to standard diagrams of brain connectivity that show how activity in one region is correlated with activity in another.

Suddenly, researchers were able to locate networks of connected brain regions where injuries caused instantaneous relief from nicotine cravings and other networks where injuries did not.

“What we’re realizing in many different fields is that our therapeutic targets are not brain regions, as we thought, but connected brain circuits,” Fox said. “If you take into account how the brain is wired, it can improve treatment.”

The study did not take into account how the patients’ home lives — how often they were exposed to cigarettes, for example — might have affected their habits. Patients considered to be in remission of addiction after their injuries usually stopped smoking immediately, reported not wanting to smoke, and did not start again while being followed up.

The researchers, however, looked at whether other changes associated with the injury—in intelligence or mood, for example—could have helped explain the disappearance of nicotine cravings in some patients. Ultimately, they didn’t seem to make a difference.

Outside experts said parts of the brain network identified in the study were familiar to them from previous research. The Doctor. Martijn Figee, a psychiatrist at the Center for Advanced Circuit Therapy at Mount Sinai in Manhattan, is studying how electrical impulses sent to the brain can treat obsessive-compulsive disorder, depression and addiction. He said addiction generally appeared to be associated with underactivity of the brain’s cognitive control circuitry and overactivity of reward-related circuits.

By applying electrical stimulation to the surface of patients’ heads or using more invasive methods such as deep brain stimulation, doctors can suppress activity in certain regions, mimicking the effect of an injury and excite activity in others. The study identified a region, called the medial frontopolar cortex, that appeared to be a good candidate for excitatory stimulation; this region coincided with the goal of a treatment recently approved by US regulators to help smokers quit.

This treatment uses an electromagnetic coil placed against the patient’s scalp to deliver electrical pulses to the surface of the brain. Other techniques involve implanting electrodes in certain regions of the brain or permanently disabling precise regions of the brain.

“This article is really interesting because it clearly indicates some accessible targets” for treatments, Figee said.

While brain stimulation has become more common in the treatment of depression and obsessive-compulsive disorder, the use of these therapies for addiction has been slower to become popular. The researchers said it would take years to perfect the techniques.

While studies show that electrical or magnetic stimulation can reduce cravings for addictive substances, it’s unclear how long these effects last. Some of the most promising targets are deep in the brain; reaching them may require deep brain stimulation or a specific type of coil that has only become available recently, Figee said.

Knowing where to direct brain stimuli also doesn’t resolve the question of which frequency to use, the scientists said. And the connections are different in different people’s brains, raising the prospect of needing tailored treatments.

People with addictions have been slower to adopt brain stimulation than people with depression or movement disorders, the researchers said, in part reflecting the taboo around thinking of addiction as a brain disorder.

There can also be structural challenges. Judy Luigjes, assistant professor of psychiatry at the University of Amsterdam Medical Centers, recruited from a pool of thousands of patients in addiction treatment centers in the Netherlands for a deep brain stimulation study. In three years, only two patients started the study.

Luigjes and colleagues wrote that patients with substance use disorder may have avoided the procedure in part because their motivation to deal with the illness fluctuated more than in patients with obsessive compulsive disorder.

And the very instability that often accompanies substance use disorders can make investing in time-intensive treatments difficult. Only one-third of patients consulting with the research team brought a family member or friend, Luigjes found.

Some scientists are working to address these concerns. A team of addicts at Mount Sinai, for example, began administering less invasive brain stimulation to patients at home or in community centers rather than in the hospital, lowering barriers to treatment.

But while the brain may be an entry point for addiction treatment, Luigjes said it was probably not the most important. Other scientists have also argued in recent years that the focus on the addiction model of brain disease has diverted attention and money away from research that addresses the social and environmental factors that contribute to addiction.

“We put a lot of our hopes, money and energy on one side,” she said, referring to the field’s focus on brain stimulation. “I don’t know if it’s going to pay off the way we thought.”

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