Scientists discover brain spot that drives risk-taking decisions

Every day, your brain runs the same calculation: take a risk or play it safe? Your gas tank might be low, but there’s just enough to make it to work on time. Do you stop and risk being late? If you’re out of money at the casino, do you quit playing slots, or withdraw more cash from the ATM? Talk to a stranger at the park or stay quiet?

Scientists at UC San Francisco and UC Berkeley have discovered the exact spot in the brain where decisions like these take shape – and, they can see each result coming half a second before a person acts.

Their study, published in Nature Neuroscience, recorded brain activity directly from the orbitofrontal cortex, a region just behind the eyes. By working with patients who already had electrodes implanted there for surgical evaluation of epilepsy, the team found two neighboring patches of the brain that signal in opposite directions, one pushing toward “do it,” the other toward “don’t.”

We’ve long suspected that this region was where the brain weighs reward against risk, but we’ve never been able to measure it while it is happening in the human brain in real time until now.”

Edward Chang, MD, Joan and Sanford I. Weill Chair of the Department of Neurological Surgery at UCSF and co-senior author of the study

The discovery could reshape how doctors treat psychiatric conditions that are characterized by an imbalance between risk-taking and caution, from depression and OCD to addiction and gambling disorders. Patients with OCD, which gives rise to intrusive thoughts and repetitive behaviors, and those with depression demonstrate excessive avoidance. This pattern may reflect an imbalance in this neural circuitry that is playing out in everyday decision-making.

A video game that reads the brain

Previous studies looking at how the brain weighs the pros and cons of a decision have mostly relied on functional magnetic resonance imaging (fMRI) scans, but the nearby sinuses distort imaging of the orbitofrontal cortex. Clara Starkweather, MD, PhD, a neurosurgery chief resident at UCSF, noticed that participants in these studies often seemed bored rather than motivated to take a risk or receive a reward.

“They’d be falling asleep, and I thought there was no way they really cared about what they were doing,” Starkweather recalls. “But then I’d see patients sitting in their beds playing Candy Crush, getting really into it.”

That intrinsic motivation is what she wanted people to feel when she was studying how their brains made decisions. So Starkweather designed her own immersive video game, where participants navigate a maze of hallways lined with bombs to try and reach glowing treasure chests. Each possible hallway contains different numbers of bombs that might explode, and possible rubies inside the chest.

“There’s just one decision point – whether you go down each hallway,” says Starkweather.

A neural tug-of-war

Instead of relying on fMRI to study people’s brain activity during the new game, Starkweather worked with patients who had electrodes implanted to treat epilepsy or psychiatric conditions and volunteered to participate in her study. The electrodes monitored brain activity on the millisecond timescale at which decisions are made.

As six patients played the game, Starkweather recorded activity from electrodes across their orbitofrontal cortices. She found that a region near the middle of the eyebrow, called the medial orbital sulcus, increased its activity just before patients took a risk such as going down a bomb-lined hallway. A patch about two centimeters over, toward the side of the eyebrow, did the opposite. Its activity spiked before patients avoided a risk, like skipping the bomb-lined hallway. The two signals moved in exact opposition to each other, down to the millisecond.

To understand how these two signals might produce a single decision, Starkweather built a computer model of their interactions. Her model proposed that the circuit behaved like a tug-of-war; one side’s signal would shoot up as the other dropped, and vice versa, with one side eventually winning out.

On easy decisions, like a hallway stacked with treasure and no bombs, the “go for it” signal won almost instantly. On harder calls, with a more even mix of risk and reward, the two signals flickered back and forth several times before settling on a final answer. Using the pattern of brain activity alone, the researchers could tell which way a patient was about to decide before they moved.

“Most models of decision-making assume the brain gradually ramps up evidence until it crosses a threshold, like a dial slowly turning,” said Robert Knight, MD, professor of Psychology and Neuroscience at UC Berkeley and co-senior author of the study. Knight worked with Starkweather on the computational modeling during the year of her residency that she spent doing research in his lab. “What we saw instead was more like a switch flipping back and forth, oscillating between two extremes until one held.”

Toward more precise psychiatric treatment

Whether someone tends to take risks or completely avoid them is central to several psychiatric conditions. People with depression, anxiety, and OCD tend to be avoidant; people with addiction or gambling disorders tend to take unhealthy risks. Brain stimulation for these conditions already targets the orbitofrontal cortex, but the region is large and the effects of treatment are inconsistent. Knowing precisely which smaller areas drive which behavior could make that stimulation far more targeted and effective.

In a related trial at UCSF led by Andrew Moses Lee, MD, PhD, and Andrew Krystal, MD, researchers stimulated brain fibers that connect to the same region that Starkweather showed is driving avoidance. That treatment could help a patient with severe, treatment-resistant OCD make more balanced decisions in real time – a difference that could be captured by the performance in Starkweather’s game.

“Right now, psychiatry mostly relies on asking people how they feel,” Starkweather said. “I want to give it something more objective: a real, measurable signature of how someone’s brain weighs risk, so treatment can target the specific circuit that’s off, in addition to a mood score.”