Decision-Making: Beyond Dopamine


by Kayt Sukel

January 17, 2012

Consider a simple matter:  what to make for breakfast on a Sunday morning. Do you grab a quick bowl of cereal, your habitual workday starter?  Or do you take your time and cook up a more princely feast of bacon and eggs? Even in this mundane, low-risk scenario, the brain is making complex calculations, weighing risks against rewards, to help you come to a decision. Neuroscientists have long known that a brain circuit called the basal ganglia, fueled by dopamine, was critical to risk and reward processing. But new research presented at the Society for Neuroscience annual conference suggests that other brain areas, as well as brain chemicals including norepinephrine and serotonin, also play an important role in helping us decide.

Exploration vs. exploitation

The old cliché, “the grass is always greener on the other side of the fence,” suggests that novelty weighs big in our decision-making. Decades of psychological research, however, have demonstrated that people gravitate towards the familiar when presented with the exploration-exploitation problem—that is, given a choice between an ambiguous option to “explore” or a known option to “exploit.” Robert Wilson, a researcher at the Neuroscience Institute at Princeton University, wondered if people would be more likely to explore new options if they were given multiple opportunities to choose.

Wilson and colleagues created a competing slot machine-type task where volunteers were told to choose the same one-eyed bandit a few times before then getting to make their own decisions 1 more, 6 more, or 11 more times. The group found that participants were more likely to explore and pick the unknown option if they had 6 more chances to decide. But once they had 11 choices, selection became random.

“We predicted that people would get more exploratory as they have more choices to make,” says Wilson. “And we found that with a few extra choices, people seek ambiguity, or the unknown. But we also found that when we gave too many choices, it turned up the noise, and then the internal calculation was dominated by the noise and individuals made a purely random decision.”

The researchers plan to test this same paradigm while measuring blood flow in the functional magnetic resonance imaging (fMRI) scanner. Wilson says they expect they will see activation in the orbitofrontal cortex (OFC) and the striatum, a part of the basal ganglia, that will correlate with ambiguity exploration. But he also expects to see activation in the brain’s norepinephrine system, in a small nucleus called the locus coeruleus (LC) during the random decisions made as participants get more and more choices.

“Previous work suggests that random exploration is driven by activity in the LC,” he says. “This area is a very tiny brain stem nucleus but it projects everywhere in the brain. And we expect that when you have too many choices, you ramp up activity in the norepiphrine system, amplify neural noise, and drive random decisions.”

Serotonin and risk aversion

Serotonin has long been implicated in mood and anxiety disorders. But researchers at the Danish Research Centre for Magnetic Resonance have found that blocking a specific serotonin receptor, the 5-HT2A type, made people less likely to make risky decisions and reduced activity in the frontal cortex when they lost what they deemed to be a low-risk turn in a gambling task.

“The serotonin 5-HT2A receptor is mainly excitatory, and widely distributed throughout the cortex,” says Macoveanu. “When participants played a gambling task and we measured brain activity, we saw a general effect of losses in the brain. A network including the ventral lateral prefrontal cortex and the medial prefrontal cortex was activated. But when we blocked the 5-HT2A receptor using a drug called ketanserin, we saw a reduction in activity in a subset of that network, in the medial prefrontal gyrus.”

Macoveanu argues that these systems are involved with risk aversion—and serotonin is important to helping us weigh those risks. “Blocking this receptor induced risk aversion in healthy participants even in low-risk activity,” he says. “And there could be wide implications for understanding risk-taking in people with mood and anxiety disorders.”

Tying the systems together

Ann Graybiel, a researcher at the Massachusetts Institute of Technology and member of the Dana Alliance for Brain Initiatives, has been studying the basal ganglia’s role in learning and decision-making for decades. Her lab is studying a neural circuit that ties the basal ganglia to the neocortex through the limbic system, which she argues, helps us be more or less positive about our respective choices.  It’s clear, she argues, that our emotions can cloud or enhance our decision-making ability, depending on a given situation and how we feel about it.

“The brain has a drive to be optimal, to help us make optimal decisions,” she says. “But let’s face it, we’re not always optimal. You break up with your boyfriend, you have a stressful day and optimality is out the window. We all understand that. Emotion is very powerful and has profound influence over how we make our decisions.”

Her lab is continuing to study this limbic circuit to help better understand how emotions, and potentially mood and anxiety disorders, play a role in how we weigh risks and rewards when making decisions. And she notes that this interesting limbic circuit is not just fueled by dopamine:  special serotonin receptors reside there, too.

“Serotonin has the power to profoundly affect these circuits, as much as dopamine,” she says. “It’s becoming more and more clear that in order to understand just how we make decisions, particularly how we make decisions when emotions are involved, we are going to have to pay careful attention to both dopamine and serotonin. It’s a very exciting time.”