DURHAM, N.C. -- Duke University Medical Centerneurobiologists have pinpointed circuitry in the brains of monkeys thatassesses the level of risk in a given action. Their findings -- gainedfrom experiments in which they gave the monkeys a chance to gamble toreceive juice rewards -- could give insights into why humanscompulsively engage in risky behaviors, including gambling, unsafe sex,drug use and overeating.
The researchers, Michael Platt, Ph.D.,and Allison McCoy, published their findings in the advanced onlineversion of Nature Neuroscience, posted August 14, 2005. The researchwas sponsored by the National Institutes of Health, the EJLBFoundation, and the Klingenstein Foundation.
In theirexperiments, the researchers gave two male rhesus macaque monkeyschances to choose to look at either of two target lights on a screen.Looking at the "safe" target light yielded the same fruit juice rewardeach time. However, looking at the "risky" target light might yield alarger or smaller juice reward. The average juice reward delivered bylooking at either target was the same.
To their surprise, themonkeys overwhelmingly preferred to gamble by looking at the riskytarget. This preference held, regardless of whether the scientists madethe risky target reward more variable, or whether the monkeys hadreceived more or less fruit juice during the course of the day.
"Therewas no rational reason why monkeys might prefer one of these optionsover the other because, according to the theory of expected value,they're identical," said Platt. The researchers also tested whether themonkeys were simply responding to the novelty of the risky target.
"Wewondered whether the monkeys preferred the risky target because theexperiment was dull and boring, and they wanted the variability," saidPlatt. "But when we made the task more interesting by changing thecolor of the lights on each trial, the monkeys didn't care anythingabout it."
In fact, when the researchers made the average payofffor the risky target less than for the safe target, "we found that theystill preferred the risky target," said Platt. "Basically these monkeysreally liked to gamble. There was something intrinsically rewardingabout choosing a target that offered a variable juice reward, as if thevariability in rewards that they experienced was in itself rewarding."
Evenwhen the researchers subjected the monkeys to a string of "losses," thehigh of a "win" appeared to keep them going, said Platt.
"If theygot a big reward one time on the risky choice, but then continued toget small rewards, they would keep going back as if they were searchingor waiting or hoping to get that big payoff. It seemed very, verysimilar to the experience of people who are compulsive gamblers. Whileit's always dangerous to anthropomorphize, it seemed as if thesemonkeys got a high out of getting a big reward that obliterated anymemory of all the losses that they would experience following that bigreward," said Platt.
Confident that they had developed a validanimal model that would reveal insights into the brain mechanism forassessing risk, the researchers next explored the neural circuitry thatgoverned that assessment. They threaded hair-thin microelectrodes intoa brain region called the posterior cingulate cortex, which studies inhumans and animals had implicated in the processing of information onrewards. They then measured the electrical activity of neurons in theregion as they administered the same behavioral task to the monkeys.
"Wefound that the neurons behaved very similarly to the monkeys," saidPlatt. "That is, as we increased the riskiness of a target, theneurons' activity would go up in the same way the monkey's frequency ofchoosing that target would go up. It was amazing the degree to whichthe activity of these neurons paralleled the behavior of the monkeys.They looked like they were signaling, in fact, the monkeys' subjectivevaluation of that target," he said. Further analysis of the neuronalactivity indicated that, indeed, the neurons were reflecting the riskvalue the monkeys placed on the target, rather than an after-the-factresponse to the payoff.
While Platt and McCoy believed they haveisolated one component of the neural machinery of risk, they do notbelieve they have mapped the entire circuitry.
"We don't thinkthe posterior cingulate cortex is by any means the only area that'simportant for assessing risk, for deciding what's valuable and foractually making a choice based on that valuation," said Platt. "Wethink that this is just part of a whole circuit that's involved in thatprocess." However, he said, pinpointing a key region involved in riskassessment will enable further studies to map that circuitry.
"It'sgoing to be interesting to trace this circuitry to see which parts ofthe brain are signaling something about subjective utility and whichparts of the brain are signaling information about true reward andpunishment experiences," said Platt.
He emphasized that suchanimal studies are a highly useful complement to human studies andgenetic studies using mice. Neuroimaging studies in humans performingsuch tasks can identify brain regions involved in making decisionsbased on risk, he said.
"And then, using these animals, we can doelectrophysiological studies that allow us to understand how thefundamental processing units of the brain -- single nerve cells --actually process information about reward and risk and uncertainty; andhow that information might contribute to the actual decision processthat results in the monkey's choice," said Platt. What's more, he said,the monkey studies allow manipulation of the circuitry using drugs todetermine how the circuitry might malfunction in human disorders.
"Forexample, it is believed that people who have low levels of theneurotransmitter serotonin might be more risk prone and impulsive,"said Platt. "Disturbances in such neurotransmitter systems might be thebasis of pathological conditions like pathological gambling,obsessive-compulsive disorder and depression. We can do pharmacologicalmanipulation of the serotonin system in monkeys to see how itinfluences risk perception and risk preferences, and whether we seechanges at the level of the single neurons that we're studying."
What'smore, said Platt, the studies with monkeys can guide studies in mice,in which scientists can make genetic alterations in the mice and studythe behavioral effects of those alterations. Such studies couldcontribute to understanding of the genetic basis of compulsivebehaviors and other such behavioral disorders.
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