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DURHAM, N.C. -- Duke University Medical Center
neurobiologists have pinpointed circuitry in the brains of
monkeys that assesses the level of risk in a given action.
Their findings -- gained from experiments in which they gave
the monkeys a chance to gamble to receive juice rewards --
could give insights into why humans compulsively 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 online version of
Nature Neuroscience, posted August 14, 2005. The research was
sponsored by the National Institutes of Health, the EJLB
Foundation, and the Klingenstein Foundation.

In their experiments, the researchers gave two male rhesus
macaque monkeys chances to choose to look at either of two
target lights on a screen. Looking at the "safe" target light
yielded the same fruit juice reward each time. However, looking
at the "risky" target light might yield a larger or smaller
juice reward. The average juice reward delivered by looking at
either target was the same.

To their surprise, the monkeys overwhelmingly preferred to
gamble by looking at the risky target. This preference held,
regardless of whether the scientists made the risky target
reward more variable, or whether the monkeys had received more
or less fruit juice during the course of the day.

"There was no rational reason why monkeys might prefer one
of these options over the other because, according to the
theory of expected value, they're identical," said Platt. The
researchers also tested whether the monkeys were simply
responding to the novelty of the risky target.

"We wondered whether the monkeys preferred the risky target
because the experiment was dull and boring, and they wanted the
variability," said Platt. "But when we made the task more
interesting by changing the color of the lights on each trial,
the monkeys didn't care anything about it."

In fact, when the researchers made the average payoff for
the risky target less than for the safe target, "we found that
they still preferred the risky target," said Platt. "Basically
these monkeys really liked to gamble. There was something
intrinsically rewarding about choosing a target that offered a
variable juice reward, as if the variability in rewards that
they experienced was in itself rewarding."

Even when the researchers subjected the monkeys to a string
of "losses," the high of a "win" appeared to keep them going,
said Platt.

"If they got a big reward one time on the risky choice, but
then continued to get small rewards, they would keep going back
as if they were searching or waiting or hoping to get that big
payoff. It seemed very, very similar to the experience of
people who are compulsive gamblers. While it's always dangerous
to anthropomorphize, it seemed as if these monkeys got a high
out of getting a big reward that obliterated any memory of all
the losses that they would experience following that big
reward," said Platt.

Confident that they had developed a valid animal model that
would reveal insights into the brain mechanism for assessing
risk, the researchers next explored the neural circuitry that
governed that assessment. They threaded hair-thin
microelectrodes into a brain region called the posterior
cingulate cortex, which studies in humans and animals had
implicated in the processing of information on rewards. They
then measured the electrical activity of neurons in the region
as they administered the same behavioral task to the
monkeys.

"We found that the neurons behaved very similarly to the
monkeys," said Platt. "That is, as we increased the riskiness
of a target, the neurons' activity would go up in the same way
the monkey's frequency of choosing that target would go up. It
was amazing the degree to which the activity of these neurons
paralleled the behavior of the monkeys. They looked like they
were signaling, in fact, the monkeys' subjective valuation of
that target," he said. Further analysis of the neuronal
activity indicated that, indeed, the neurons were reflecting
the risk value the monkeys placed on the target, rather than an
after-the-fact response to the payoff.

While Platt and McCoy believed they have isolated one
component of the neural machinery of risk, they do not believe
they have mapped the entire circuitry.

"We don't think the posterior cingulate cortex is by any
means the only area that's important for assessing risk, for
deciding what's valuable and for actually making a choice based
on that valuation," said Platt. "We think that this is just
part of a whole circuit that's involved in that process."
However, he said, pinpointing a key region involved in risk
assessment will enable further studies to map that
circuitry.

"It's going to be interesting to trace this circuitry to see
which parts of the brain are signaling something about
subjective utility and which parts of the brain are signaling
information about true reward and punishment experiences," said
Platt.

He emphasized that such animal studies are a highly useful
complement to human studies and genetic studies using mice.
Neuroimaging studies in humans performing such tasks can
identify brain regions involved in making decisions based on
risk, he said.

"And then, using these animals, we can do
electrophysiological studies that allow us to understand how
the fundamental processing units of the brain -- single nerve
cells -- actually process information about reward and risk and
uncertainty; and how that information might contribute to the
actual decision process that results in the monkey's choice,"
said Platt. What's more, he said, the monkey studies allow
manipulation of the circuitry using drugs to determine how the
circuitry might malfunction in human disorders.

"For example, it is believed that people who have low levels
of the neurotransmitter serotonin might be more risk prone and
impulsive," said Platt. "Disturbances in such neurotransmitter
systems might be the basis of pathological conditions like
pathological gambling, obsessive-compulsive disorder and
depression. We can do pharmacological manipulation of the
serotonin system in monkeys to see how it influences risk
perception and risk preferences, and whether we see changes at
the level of the single neurons that we're studying."

What's more, said Platt, the studies with monkeys can guide
studies in mice, in which scientists can make genetic
alterations in the mice and study the behavioral effects of
those alterations. Such studies could contribute to
understanding of the genetic basis of compulsive behaviors and
other such behavioral disorders.