Addiction on the Brain

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Would you prefer $18 right now, or $20 next month? The way the human brain makes such decisions varies significantly from person to person, according to a just-published study that provides new insights into the neurological basis of drug addiction.

The brain activity of individuals who tend to act on impulse is strikingly different from that of people who choose to delay gratification, according to behavioral neuroscientist Charlotte Boettiger of the University of North Carolina. She goes on to report that alcoholics overwhelmingly fall on the impulsive side of the spectrum — a finding that suggests an ingrained pattern of brain activity may lead to a greater likelihood of addiction.

“Taking action without regard to long-term consequences is a diagnostic characteristic of alcoholism and other addictive disorders,” said Boettiger, who led the research project at the University of California, San Francisco. “Despite the clinical importance of this kind of impulsive behavior, little is known about how the brain either generates or suppresses impulsive decision-making. This study was designed to try to shed light on that issue.”

Using functional MRI technology, Boettiger and her colleagues scanned the brains of nine recovering alcoholics and 10 people with no history of substance abuse. The subjects were asked a series of questions that involved choosing between immediate gratification and a greater reward at a later date.

“Alcoholics were much more likely to take the immediate reward,” she reported. “There’s a range within each group, but the groups were significantly different from one another.”

As were their brain scans.

Boettiger was particularly interested in the activity of the lateral orbital frontal cortex, which she described as “the part of our brain right above our eye sockets. It’s an area that many studies have identified as being abnormal in some way or other in addicts.

“We found that people who showed very high activity in that area tended to be willing to wait for a delayed reward. People with low activity there during decision-making tended to not be willing to wait for a reward. One possibility is that this area might be necessary for creating strong mental representations of the long-term consequences of our actions.”

She found the same lowered activity in the orbital frontal context in the more impulsive non-addicts — but did not find it in the one alcoholic (out of the group of nine) who was more deliberate in his decision-making. This suggests the brain-activity patterns are probably not caused by the drug use, but rather that some people are programmed to act more impulsively, which puts them at greater risk of becoming addicts.

In light of these new insights, “It will be interesting to study various sorts of therapeutic interventions,” she said. “If we could find a drug that would elevate activity in the orbital frontal cortex during decision-making, it’s possible that could be a good candidate for supportive medical treatment for addicts. There are a lot of drugs currently available that I think would be worth testing.

“It hasn’t been very popular within the pharmaceutical industry to pursue medications for addiction,” she added. “I’m hopeful that will change. I think there’s a misconception within the pharmaceutical industry that this is not a profitable market. I think there’s a large market out there looking for help.”

Another finding that intrigued Boettiger — and may entice the drug industry — involves the level of dopamine in the brains of alcoholics. The research subjects who tended to choose immediate gratification were more likely to have a specific gene mutation that leads to lower levels of dopamine, a neurotransmitter that helps regulate emotions.

“The alcoholics in our study who have that low-dopamine (mutation) were the most impulsive choosers in our group,” she reported. “Our data suggests that having low dopamine there makes (certain areas of the brain) process calculations inefficiently.” That inefficiency, she added, may help explain why addicts have such difficulty focusing on how their present-day behavior will manifest in the future.

Boettiger calls this mixture of reduced frontal cortex activity and lower dopamine levels “a double whammy.” But the dopamine part of the equation also offers hope for a new type of treatment. “Elevating dopamine may end up being a great supportive therapy,” she said. “I would like to see that happen. I would like to test whether medications that elevate dopamine change behavior. Our data strongly predicts that it would.”

Boettiger plans to follow up this research with pharmacological studies, as well as by looking at brain-activity patterns of people who have a family history of alcoholism, but have yet to show any symptoms. That study could show whether impulse-oriented brain-activity patterns are hereditary. “I would hope to do that in the next year,” she said.

If that research proves her hypothesis, Boettiger can envision a day when we routinely scan the brains of children born into families where addictions are common. “I think it’s important for kids to be warned early that they are at risk,” she said. “This may be another tool.”

In addition to such early warnings and potential drug treatments, Boettiger believes these findings could help refine talk therapy for addictions. “A lot of behavioral therapies used to treat addicts today focus on helping people strengthen their mental representations of the long-term consequences of drinking or drug abuse,” she noted. “It would be interesting to see whether that therapy changes brain-activity patterns.

“I know (Alcoholics Anonymous) has helped many people, but it was designed in the 1930s,” she added. “I think we have learned some things that we didn’t know then.”

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