Published online 6 December 2007 | Nature | doi:10.1038/news.2007.358

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The gene that makes us once bitten, twice shy

A single mutation helps to determine whether we repeat our mistakes.

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Most people tend to learn from their mistakes and avoid making the same blunder twice. Now research reveals a genetic mutation that helps to determine the extent to which certain people are doomed to repeat history.

Drug addicts, alcoholics and compulsive gamblers are known to be more likely than other people to have this genetic mutation, which leaves them with fewer receptors of a certain type in the brain. These receptors — called D2 receptors — are activated when levels of the neurotransmitter dopamine drop.

Dopamine is responsible for signalling fun and pleasure in the brain. But dopamine also helps us learn. When we make a pleasurable decision, dopamine is a chemical treat, urging the brain to repeat the choice. Being deprived of such a treat should theoretically activate D2 receptors and encourage people not to make that same decision again.

So it had been theorized that people with fewer D2 receptors might be less capable of learning from negative reinforcement.

Avoid the frowns

To test this, Tilmann Klein and Markus Ullsperger at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, looked at the decision-making of 26 men, while monitoring their brains with a magnetic resonance imaging scanner. Twelve of the volunteers had the gene mutation for low numbers of D2 receptors. The researchers chose men because dopamine levels change during a woman’s menstrual cycle, which would have complicated the study.

Volunteers were presented with sets of two symbols on a computer screen, and were asked to select one. After making a choice, either a smiley face or a frown flashed on the screen, providing positive or negative feedback. The results weren't uniform: symbol 'A' was the most positively reinforced, resulting in a smile 80% of the time, while 'B' was the most negatively reinforced, prompting a frown in 80% of trials. Other characters, C through F, spurred responses somewhere in between.

The team next tested whether the volunteers learned to choose symbol 'A' — indicating learning from positive reinforcement — and avoid symbol 'B' — indicating learning by negative reinforcement.

Both sets of volunteers learned to choose symbol A. But the men with fewer D2 receptors had trouble learning from the scolding, the team reports today Science1.

Complex decisions

Brain imaging confirmed the brain regions thought to be involved in learning from mistakes. A brain area called the rostral cingulate zone was more active in the volunteers with normal D2 levels during the learning sessions, compared to those with the D2 mutation. A brain region key to forming memories, the hippocampus, was also more active in the volunteers with normal D2 levels.

It is important to remember that real-life decisions are based on much more than the response of D2 brain receptors, says Ullsperger. But it seems to have some effect on our ability to learn from mistakes.

Unravelling how we learn good choices from bad ones will help explain how addiction and compulsive behaviour are processed in the brain, says Michael Frank, a neuroscientist at the University of Arizona in Tucson.

The brains of addicts may be tilted against learning from mistakes, says Frank. They're wired to sense the good, such as drug-induced euphoria or a hot streak at the blackjack table, but ignore the losses or consequences. “It's a recipe for disaster,” he says. 

  • References

    1. Klein, T. A. et al. Science 318, 1462-1465 (2007).
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