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A scan of an injured brain often creates a map of irretrievable losses and shows spots where damage is causing memory difficulties or tremors.
But in rare cases, these scans can reveal just the opposite: diagrams of brain regions where an injury miraculously relieves a person’s symptoms, and clues into how doctors might accomplish the same thing.
A team of researchers has now taken a new look at a series of such brain images taken from nicotine-addicted cigarette smokers whose stroke or other injury spontaneously helped them quit smoking. The results, the scientists said, revealed a network of interconnected brain regions that they believe underpin addiction-related disorders that may affect tens of millions of Americans.
The study, published Monday in the journal Nature Medicine, supports an idea that has recently gained traction: that addiction doesn’t live in one brain region or another, but in a circuit of regions connected by filamentous nerve fibers.
The findings could provide a clearer set of targets for addiction treatments that deliver electrical impulses 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 is the main problem that we should be addressing with treatment,” said Dr. Juho Joutsa, one of the lead authors of the study and a neurologist at the University of Turku in Finland. “We hope that afterwards we will have a very good idea of these regions and networks.”
Research over the past two decades has solidified the idea that addiction is a brain disorder. But many people still believe that addiction is voluntary.
Some independent experts said the latest study was an unusually powerful demonstration of the brain’s role in substance use disorders. Among smokers who have 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 injury patients who undertook a risk assessment for alcoholism. The brain network associated with a lower risk of alcohol addiction was similar to that alleviating nicotine addiction, suggesting the circuitry 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 associate director of the Office of National Drug Control Policy, which does not was involved in the study. “It dispels so many stereotypes that still permeate the field of addiction: Addiction is bad parenting, addiction is weak personality, addiction is a lack of morals.”
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In recent years, a number of studies had identified specific brain regions where a lesion or injury appeared to be associated with breaking free from addiction. But the goals kept shifting.
“People have not been successful in showing consistency in the affected areas,” said Dr. Hamed Ekhtiari, addiction treatment expert at the Laureate Institute for Brain Research in Tulsa, Oklahoma.
In the new study, Dr. Joutsa applied sophisticated statistical techniques to an old series of brain scans of Iowa smokers who had suffered neural injuries. A previous analysis of the same scans had suggested that patients with damage to the insula, a brain region involved in conscious urges, were more likely to quit smoking.
But dr Joutsa, going through the same scans pixel by pixel, noted that many patients without insula injuries had also lost the urge to smoke. “It was something in the Insula story, but it wasn’t the whole story,” he said.
In cooperation with dr. Michael Fox, associate professor of neurology at Harvard Medical School, examined Dr. Joutsa a second set of scans of smokers who had strokes in Rochester, NY. In total, they examined 129 cases.
The team strived to find individual brain regions where injuries reliably helped patients quit smoking. Instead, the researchers turned to standard brain connectivity diagrams that depict how activity in one region correlates with activity in another.
Suddenly, the researchers were able to pinpoint networks of connected brain regions where injury produced immediate relief from nicotine cravings, and other networks where injury did not.
“What we’re realizing in many different areas is that our therapeutic targets aren’t brain regions, as we used to think, but interconnected circuits in the brain,” said Dr. Fox. “By considering how the brain is connected, you can improve treatment.”
The study did not take into account how the patients’ home life – how often they were exposed to cigarettes, for example – might have affected their habits. Patients who were thought to have gone into addiction remission from their injuries generally quit smoking immediately, reported not feeling an urge to smoke, and did not start smoking again while being monitored.
However, the researchers looked at whether other changes associated with the injury — for example, in intelligence or mood — might have helped explain the disappearance of nicotine cravings in some patients. They didn’t seem to make any difference in the end.
Outside experts said they were familiar with parts of the brain network identified in the study from previous research. dr Martijn Figee, a psychiatrist at the Center for Advanced Circuit Therapeutics at Mount Sinai in Manhattan, is studying how electrical impulses delivered to the brain can treat obsessive-compulsive disorder, depression and addiction. He said that addiction in general appears to be associated with under-activity of the brain’s cognitive circuitry and over-activity of reward-related circuits.
By applying electrical stimulation to the surface of the patient’s head, or by using more invasive methods such as deep brain stimulation, physicians can suppress activity in certain regions, mimicking the effects of an injury, and stimulate 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 overlapped with the target of a treatment recently approved by US regulators to help smokers quit.
This treatment uses an electromagnetic coil placed on a patient’s scalp to deliver electrical impulses to the surface of the brain. Other techniques involve implanting electrodes in specific brain regions or permanently deactivating specific brain regions.
“This paper is really interesting in that it clearly outlines some accessible targets for treatments,” said Dr. fiee
While brain stimulation has become more widely used to treat depression and obsessive-compulsive disorder, the use of these therapies for addiction has been slower. Researchers said it would take years to refine the techniques.
Although studies show that electrical or magnetic stimulation can reduce cravings for addictive substances, it’s not clear how long these effects last. Some of the most promising targets are deep in the brain; Achieving them may require deep brain stimulation or a specific type of coil that only recently became available, said Dr. fiee
Knowing where to direct brain stimulation doesn’t solve the question of what frequency to use either, the scientists said. And the connections are different in different people’s brains, increasing the likelihood that treatments will need to be tailored.
People with addictions have been slower to adopt brain stimulation than people with depression or movement disorders, the researchers said, partly reflecting the taboo on viewing addiction as a brain disorder.
Structural challenges can also arise. Judy Luigjes, assistant professor of psychiatry at the University of Amsterdam Medical Centers, recruited from a pool of thousands of patients at addiction treatment centers in the Netherlands for a study of deep brain stimulation. In three years, only two patients entered the study.
dr Luigjes and her colleagues wrote that patients with substance use disorders may have avoided the procedure in part because their motivation for addressing the disorder varied more than in patients with OCD.
And the very instability that often accompanies substance use disorders can make investing in time-consuming treatments difficult. Only a third of patients with an appointment with the research team brought a family member or friend with them, noted Dr. Luigje’s feast.
Some scientists are working to address these concerns. An addiction team at Mount Sinai, for example, has begun giving patients less invasive brain stimulation at home or in community centers rather than in the hospital, lowering treatment barriers.
But while the brain could be an entry point for treating addiction, Dr. Luigjes that it is probably not the most important. Other scientists, too, have argued in recent years that the focus on the brain disorder addiction model has diverted attention and money from research looking at social and environmental factors that contribute to addiction.
“We’ve put too much of our hopes, money and energy into one site,” she said, referring to the field’s focus on brain stimulation. “I don’t know if it will pay off the way we envisioned it.”
