They were cigarette smokers. Then a stroke defeated their addiction.

They were cigarette smokers.  Then a stroke defeated their addiction.
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Taking a CT scan of an injured brain often produces a map of irreparable loss, revealing where the damage is causing memory impairment or tremors.

But in rare cases, these scans can reveal the exact opposite: slivers of brain regions where an injury miraculously relieves someone’s symptoms, offering clues as to how doctors might accomplish the same thing.

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

The studypublished Monday in the scientific journal Nature Medicine, supports an idea that has recently caught on: that addiction does not live in one region of the brain or another, but rather in a circuit of regions connected by threadlike nerve fibers.

The findings could provide a clearer set of goals 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 the main problem is in the brain that we should be targeting with treatment,” said Dr Juho Joutsa, one of the lead authors of study and neurologist at the University. from Turku in Finland. “Hopefully after that we’ll have a really good idea of ​​those 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 exceptionally powerful demonstration of the role of the brain in substance use disorders. Among smokers who had strokes or other brain damage, those who damaged a particular neural network experienced immediate relief from their cravings.

The researchers replicated their findings in a separate group of brain-damaged patients who completed an alcoholism risk assessment. The brain network associated with a lower risk of alcohol dependence was similar to that which relieved nicotine addiction, suggesting that 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 deputy director of the Office of National Drug Control Policy, which was not involved in the study. “It puts an end to so many of the stereotypes that still permeate the field of addiction: that addiction is bad parenting, addiction is weak personality, addiction is lack of morality.”

Over the past few years, a succession of studies have identified particular brain regions where damage, or injury, appears to be associated with the relief of addiction. But the targets kept changing.

“People have failed to show consistency in the areas involved,” said Dr. Hamed Ekhtiari, an addiction treatment expert at the Laureate Institute for Brain Research in Tulsa, Okla.

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

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

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

The team struggled to find individual brain regions where injuries reliably helped patients quit smoking. Instead, the researchers turned to standard diagrams of brain connectivity that show how activity in one region correlates with activity in another.

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

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

The study did not take into account how the patients’ home life – how often they were exposed to cigarettes, for example – may have affected their habits. Patients deemed to have gone into remission after their injuries generally quit smoking immediately, reported not cravings, and did not start again during their follow-up.

The researchers, however, investigated whether other changes associated with the injury — in intelligence or mood, for example — might have helped explain the disappearance of nicotine cravings in some patients. They ultimately 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. Dr. Martijn Figee, a psychiatrist at the Center for Advanced Circuit Therapeutics at Mount Sinai in Manhattan, studies how electrical impulses delivered to the brain can treat obsessive-compulsive disorder, depression and substance abuse. He said addiction generally seemed 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 like deep brain stimulation, doctors can suppress activity in certain regions, mimicking the effect of injury and excite activity. in other. The study identified a region, called the medial frontopolar cortex, that appeared to be a good candidate for excitatory stimulation; this region straddled the target of a treatment recently approved by US regulators to help smokers quit.

This treatment uses an electromagnetic coil placed against a patient’s scalp to deliver electrical impulses to the surface of the brain. Other techniques involve the implantation of electrodes in certain regions of the brain or the permanent deactivation of specific regions of the brain.

“This paper is really interesting in that it clearly points to some accessible targets” for treatments, Dr. Figee said.

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

Despite studies showing that electrical or magnetic stimulation can reduce the craving for addictive substances, it is not known how long these effects last. Some of the most promising targets lie deep within the brain; Reaching them may require deep brain stimulation or a specific type of coil that has only recently become available, Dr. Figee said.

Knowing where to direct brain stimulation also doesn’t solve the question of which frequency to use, the scientists said. And the connections are different in the brains of different people, suggesting the need for tailored treatments.

According to the researchers, people with addictions were slower to adopt brain stimulation than those with depression or movement disorders, which partly reflects the taboo surrounding the perception of addiction as a brain disorder.

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

Dr Luigjes and his colleagues wrote that patients with substance use disorders may have avoided the procedure in part because their motivation to treat the disease fluctuated more than in patients with obsessive-compulsive disorder.

And the very instability that often accompanies substance use disorders can make it harder to invest in time-consuming treatments. Only a third of patients with an appointment with the research team brought a family member or friend, Dr Luigjes found.

Some scientists are working to address these concerns. A drug addiction team at mount sinaifor example, began delivering less invasive brain stimulation to patients at home or in community centers rather than in hospital, reducing barriers to treatment.

But while the brain could be an entry point for addiction treatment, Dr. Luigjes said it’s probably not the most important. Other scientists have also sustained in recent years that focusing on the brain disease model of addiction has diverted attention and money from research on the social and environmental factors that contribute to addiction.

“We put too much hope, money and energy into one side,” she said, referring to the field’s focus on brain stimulation. “I don’t know if it will pay off as we thought.”

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