Dec. 30, 2007 Scientists have for the first time identified brain sites that fire up more when people make impulsive decisions. In a study comparing brain activity of sober alcoholics and non-addicted people making financial decisions, the group of sober alcoholics showed significantly more "impulsive" neural activity.
The researchers also discovered that a specific gene mutation boosted activity in these brain regions when people made impulsive choices. The mutation was already known to reduce brain levels of the neurotransmitter dopamine. The newly found link involving the gene, impulsive behavior and brain activity suggests that raising dopamine levels may be an effective treatment for addiction, the scientists say.
Lead scientist is Charlotte Boettiger, PhD, assistant professor of psychology at the University of North Carolina at Chapel Hill. Boettiger led the research as a scientist at UCSF's Ernest Gallo Clinic and Research Center. Senior author is Howard Fields, MD, PhD, a UCSF professor of neurology and an investigator in the Gallo Center.
"Our data suggest there may be a cognitive difference in people with addictions," Boettiger said. "Their brains may not fully process the long-term consequences of their choices. They may compute information less efficiently."
"What's exciting about this study is that it suggests a new approach to therapy. We might prescribe medications, such as those used to treat Parkinson's or early Alzheimer's disease, or tailor cognitive therapy to improve executive function" she added.
"I am very excited about these results because of their clinical implications," Fields said. "The genetic findings raise the hopeful possibility that treatments aimed at raising dopamine levels could be effective treatments for some individuals with addictive disorders."
The scientists used functional magnetic resonance imaging, or fMRI, to image brain activity while subjects were faced with a hypothetical scenario: choose less money now, or more money later.
Boettiger recruited 24 subjects:19 provided fMRI data, 9 were recovering alcoholics in abstinence and 10 had no history of substance abuse. Another five were included in the genotyping analysis.
At the fMRI research facility at the University of California, Berkeley, financial decision tasks measured rational thinking and impulsivity. Sober alcoholics chose the "now" reward almost three times more often than the control group, reflecting more impulsive behavior.
While decisions were being made, the imaging detected activity in the posterior parietal cortex, the dorsal prefrontal cortex, the anterior temporal lobe and the orbital frontal cortex. People who sustain damage to the orbital frontal cortex generally suffer impaired judgment, manage money poorly and act impulsively, the scientists noted.
The study revealed reduced activity in the orbital frontal cortex in the brains of subjects who preferred "now" over "later," most of whom had a history of alcoholism.
The orbital frontal cortex activity may be a neural equivalent of long-term consequences, Fields said.
"Think of the orbital frontal cortex as the brakes," Boettiger explained. "With the brakes on, people choose for the future. Without the brakes they choose for the short-term gain."
The dorsal prefrontal cortex and the parietal cortex often form cooperative circuits, and this study found that high activity in both is associated with a bias toward choosing immediate rewards.
The frontal and parietal cortexes are also involved in working memory -- being able to hold data in mind over a short delay. When asked to choose between $18 now or $20 in a month, the subjects had to calculate how much that $18 (or what it could buy now) would be worth in a month and then compare it to $20 and decide whether it would be worth the wait.
The parietal cortex and the dorsal prefrontal cortex were much more active in people unwilling to wait. This could mean, Boettiger said, that the area is working less efficiently in those people.
The researchers also focused on a variant of a gene called COMT. The mutation is associated with lower dopamine levels, and the study showed that people with two copies of this allele (resulting in the lowest dopamine levels) had significantly higher frontal and parietal activity and chose "now" over "later" significantly more often.
"We have a lot to learn," Boettiger said. "But the data takes a significant step toward being able to identify subtypes of alcoholics, which could help tailor treatments, and may provide earlier intervention for people who are at risk for developing addictions."
The bigger picture, she added, is that her study provides more evidence that addiction is a disease, something even some of her peers don't yet believe.
"It's not unlike chronic diseases, such as diabetes," she said. "There are underlying genetic and other biological factors, but the disease is triggered by the choices people make."
"It wasn't that long ago that we believed schizophrenia was caused by bad mothers and depression wasn't a disease. Hopefully, in 10 years, we'll look back and it will seem silly that we didn't think addiction was a disease, too."
The research is reported in the Dec. 26, 2007 issue of the "Journal of Neuroscience."
Co-authors on the paper are: Jennifer Mitchell, Vanessa Tavares, Margaret Roberston and Geoff Joslyn at the Gallo Center, and Mark D'Esposito at the University of California, Berkeley.
The research was supported by the U.S. Department of Defense and the UCSF Wheeler Center for the Neurobiology of Addiction.
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