Taking a scan of an injured brain often produces a map of irreparable losses, revealing spots where the damage is causing memory problems or tremors.
But in rare cases, those scans can reveal just the opposite: plots of areas of the brain where an injury miraculously relieves a person’s symptoms, and provide clues as to how doctors can accomplish the same thing.
A team of researchers has now taken a fresh look at a series of such brain images from cigarette smokers addicted to nicotine whose strokes or other injuries helped them quit spontaneously. The results, the scientists said, showed a network of interconnected brain regions that they believe underlie addiction-related conditions that may affect tens of millions of Americans.
The studyPublished Monday in the scientific journal Nature Medicine, it supports an idea that has recently gained traction: that addiction does not live in one brain region or the other, but rather in a circuit of regions connected 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 is the biggest problem we should target with treatment,” says Dr. Juho Joutsa, one of the study’s lead authors and a neurologist at the university. from Turku in Finland. “We hope that after this we will have a very good picture of those regions and networks.”
Research over the past two decades has reinforced the idea that addiction is a brain disease. 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 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 completed a risk assessment for alcoholism. The brain network associated with a lower risk of alcohol dependence was similar to the network that alleviated nicotine dependence, suggesting that the circuitry may underlie a broader set of dependencies.
“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 ends so many of the stereotypes that still permeate the field of addiction: that addiction is bad parenting, addiction is a weak personality, addiction is a lack of morality.”
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In recent years, a succession of studies had identified certain brain regions where a lesion or injury appeared to be associated with addiction relief. But the goals kept shifting.
“People had 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 advanced statistical techniques to an old series of brain scans of smokers in Iowa 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, who went through the same scans pixel by pixel, noted that many patients without an insula injury had also lost the urge to smoke. “There was something about the insula story, but it wasn’t the whole story,” he said.
In collaboration with Dr. Michael Fox, an associate professor of neurology at Harvard Medical School, examined Dr. Joutsa conducted a second set of scans of smokers who had suffered a stroke in Rochester, NY. In total, they looked at 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 map how activity in one region correlates with activity in another.
Suddenly, the researchers were able to locate networks of connected brain regions where injuries caused immediate relief from nicotine cravings and other networks where injuries did not.
“What we realize in many different areas is that our therapeutic targets are not areas of the brain, as we once thought, but connected brain circuits,” said Dr. Fox. “If you take into account the way the brain is connected, you can improve treatment.”
The study did not take into account how patients’ home lives — how often they were exposed to cigarettes, for example — may have affected their habits. Patients considered to have entered addiction remission after their injuries generally quit smoking immediately, reported no urge to smoke, and did not restart while being monitored.
However, the researchers looked at whether other changes linked to the injury — to intelligence or mood, for example — could 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 parts of the brain network identified in the study were known 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 addiction. He said addiction generally appeared to be associated with underactivity of the brain’s cognitive control circuitry and overactivity of reward-related circuitry.
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, mimic the effect of an injury, and induce activity in other areas. The study identified one region, called the medial frontopolar cortex, that appeared to be a good candidate for excitatory stimulation; that region overlapped with the target of a treatment recently approved by US regulators to help smokers quit.
That treatment uses an electromagnetic coil placed against a patient’s scalp to deliver electrical pulses to the surface of the brain. Other techniques include implanting electrodes in specific brain regions or permanently deactivating precise brain regions.
“This article is really interesting because it clearly outlines some accessible targets” for treatments, said Dr. figee.
While brain stimulation has become more common for the treatment of depression and obsessive compulsive disorder, the use of those therapies for addiction has slowed down. Researchers said it would take years to hone the techniques.
Despite studies showing that electrical or magnetic stimulation can reduce cravings for addictive substances, it’s not clear how long those effects last. Some of the most promising targets are located deep in the brain; reaching them may require deep brain stimulation or a specific kind of coil that only recently became available, said Dr. figee.
Knowing where to send brain stimulations also doesn’t solve the question of what frequency to use, scientists say. And the connections are different in different people’s brains, raising the prospect of treatments having to be tailored.
People with addictions were slower to embrace brain stimulation than those with depression or movement disorders, researchers said, partly reflecting the taboo surrounding thinking of addiction as a brain disorder.
There may also be structural challenges. Judy Luigjes, an assistant professor of psychiatry at the UMCs of Amsterdam, recruited from a pool of thousands of patients in 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 an addiction disorder may have avoided the procedure in part because their motivation to manage the disease fluctuated more than patients with obsessive-compulsive disorder.
And the very instability that often accompanies substance use disorders can make investing in time-consuming treatments more difficult. Only a third of patients who had an appointment with the study team brought a family member or friend, Dr. lazy.
Some scientists are working to allay those concerns. A addiction team on Mount Sinaifor example, it has been decided to administer less invasive brain stimulation to patients at home or in community centers rather than in the hospital, thereby lowering the threshold for treatment.
But while the brain can be an entry point for addiction treatment, said Dr. Silly that this probably wasn’t the most important. Other scientists have argued in recent years that the focus on the brain disease model of addiction has diverted attention and money from research on social and environmental factors that contribute to addiction.
“We’ve put too much of our hopes, 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 out the way we thought it would.”
