To get from experience to emotion, the brain hits ‘sustain’

Get cut off in rush-hour traffic and you may feel angry for the whole trip, or even snap at a noisy child in the back seat.

Get an unexpected smile from that same kid and you may feel like rush hour — and even those other drivers — aren’t so bad.

“The thing about emotion is it generalizes. It puts the brain into a broader state,” says Dr. Karl Deisseroth, a psychiatrist and professor at Stanford University.

Deisseroth and a team of researchers have come up with an explanation for how that happens.

The process involves a signal that, after a positive or negative experience, lingers in the brain, the team reports in the journal Science.

Experiences themselves act a bit like piano notes in the brain. Some are staccato, producing only a brief burst of activity that may result in a reflexive response, like honking at another driver, or smiling back at a child.

But more profound experiences can be more like a musical note that is held with the sustain pedal and still audible when the next note is played, or the one after that.

“You just need it to be sustained long enough to merge with and interact with other notes,” Deisseroth says. “And from our perspective, this is exactly what emotion needs.”

If the team is right, it could help explain the emotional differences seen in some neuropsychiatric conditions.

People on the autism spectrum, for example, often have trouble recognizing emotions in others, and regulating their own emotions. Schizophrenia can cause mood swings and reduced emotional expression.

But some researchers question whether this lingering signal is specific to emotion, a term with no agreed-upon definition in the scientific world.

“Sure, [a sustained signal] happens in emotion,” says Lisa Feldman Barrett, a professor of psychology at Northeastern University. “But it also happens in all kinds of other instances,” like when a person is concentrating or remembering.

Emoting in the lab

Deisseroth and his team set out to recreate the sort of experience that leads to an emotional response, but could be observed in a lab.

“We wanted something that would cause a negative emotion but wouldn’t be painful,” he says.

They chose a puff of air, delivered to the cornea. That meant they could use a machine that eye doctors use to detect glaucoma.

The puff from this device is “certainly annoying, certainly aversive, but not painful,” Deisseroth says.

The team also thought it might provoke the same response in mice, an animal that predates humans by millions of years.

It turned out that both mice and people blink reflexively in response to a puff. Both species also respond to multiple puffs by squinting to protect their eyes.

Next, the team studied the brain activity associated with these experiences. And they found two distinct phases involving different brain circuits.

The first phase is like a staccato note on a piano. In the first two-tenths of a second after a puff, there’s a spike in the activity of brain circuits that process sensory input.

The second phase is more like a piano note held by the sustain pedal. During this period, activity appears in other circuits, including those involved in emotion.

When mice and people were exposed to puffs of air again and again — and again — this sustained response got stronger with each stimulus.

Behavior changed too. Both mice and people squinted more, and the people reported that they were more annoyed by the experience.

“In the mice, although we don’t get those verbal reports, we saw this crucial generalization,” Deisseroth says. “It made them less likely to seek out rewards.”

That behavior, a failure to look for food and other rewards, is a sign of stress or some other negative state in mice.

Enter Ketamine

To confirm the finding, the team did the experiment again. But this time, both mice and people received an anesthetic called ketamine. They thought the drug might disconnect a negative sensory experience from any emotional response it would ordinarily produce.

On ketamine, the second, sustained phase of brain activity was no longer present, and responses to the air puffs changed.

Mice and people would still blink reflexively after a puff of air. But they didn’t squint. And people reported that they no longer found the puffs of air annoying.

“If you remove this sustain phase, you block the emotional response as well,” Deisseroth says.

Sort of, Barrett says.

The study shows that persistent signals in the brain play a role in altering a person or animal’s brain state, she says. But that brain state could be consciousness or focus, rather than an emotion.

Ketamine, she says, interferes with all of these states.

“That tells us that the way that the brain creates emotion is how it creates everything else — how it creates thoughts, how it creates perceptions, how it creates actions,” Barrett says. “It’s not doing something special in emotion.”

Barrett also thinks the air puffs probably mean something different to a mouse than to a person.

“The human brain has this capacity to abstract, to create meanings that go beyond motor and sensory differences,” she says.

Barrett’s concerns about how emotions are studied extends to lots of other research.

The underlying problem, she says, is that scientists have yet to agree on a common definition of an emotion.