How emotions build in the brain - and why they linger

We often don’t realize it, but emotions shape nearly every decision we make. They help us navigate through daily life, influencing the actions we take and the choices we consider.

When emotions work as they should, they guide us safely. But when they linger too long or strike at the wrong time, they can create problems.

Despite decades of research, scientists still have much to learn about how the brain generates emotions. How does a fleeting feeling become a lasting state? And why do these emotional states sometimes turn into challenges that are hard to shake?

Tracing emotions in the brain

New research from Stanford Medicine offers some important answers. A team of neuroscientists and psychiatrists has mapped the brain’s response to an unpleasant sensory experience.

The experts found patterns of brain activity that are not only key to human emotion but are also shared with mice – and likely with all mammals. The findings could improve our understanding of neuropsychiatric conditions marked by emotional difficulties.

“Emotional states are fundamental to psychiatry,” said Dr. Karl Deisseroth, a professor of behavioral sciences who led the study.

The research was primarily focused on investigating how the brain responds to negative sensory experiences. Dr. Deisseroth suspects, however, that the observed patterns could apply to positive experiences too.

The challenge of a big brain

Mammals, including humans and mice, have large brains compared to other animals. A mouse brain contains about 100 million neurons. A human brain has close to 90 billion neurons – nearly one thousand times more.

“A bigger brain means a richer, more complex mental life. But there are real constraints once you scale up,” noted Dr. Deisseroth. For humans, size comes with a problem: it takes time for information to travel across the brain and be properly integrated.

To make a good decision, the brain has to pull together sensory information – goals, bodily needs, and other data – all at once. If it can’t integrate everything, mistakes happen. Emotions may help by holding information together long enough for the brain to sort it out.

“Tuning the time scale of this communication could be an important aspect of typical brain function,” said Dr. Ethan Richman, co-lead author of the study.

He compared it to a piano’s sustain pedal, which lets notes linger longer after being played. In the brain, too much or too little persistence could disrupt emotional processing and contribute to disorders.

From mice to humans

Human brain activity is famously complex. To find meaningful patterns, the team needed a way to sort through the noise. Dr. Deisseroth, known for developing optogenetics, left that technique aside for this study. Instead, the researchers used a clever evolutionary trick.

The team compared brain activity in humans and mice – two species that share a common ancestor from 70 million years ago. They looked for patterns that showed up in both species when exposed to the same stimulus, linked to the same behaviors, and affected by the same interventions.

“This approach allowed us to focus our study on the key principles that were shared between mice and humans,” said Dr. Isaac Kauvar, co-lead author of the study.

If a brain pattern has been preserved across millions of years, it’s likely important for survival, noted Dr. Deisseroth.

A simple puff of air

To trigger emotions safely and reliably, the team needed a non-harmful stimulus. They turned to something familiar from eye exams: a puff of air to the eye. It’s not painful, but it is mildly unpleasant.

Participants in the study – patients at Stanford Hospital undergoing monitoring for epilepsy – described the puffs as “annoying,” “unpleasant,” and “uncomfortable.” A series of these puffs made them feel increasingly irritated.

“That bummed-out state of mind can be adaptive,” said Dr. Deisseroth. Repeated negative experiences teach the brain to guide future behavior carefully.

How the brain responds to emotions

The researchers were able to record high-resolution brain activity using electrodes implanted in patients’ brains for clinical reasons. These patients, confined to their hospital beds, volunteered for the study while awaiting seizure events.

In response to the air puffs, subjects first blinked reflexively. Then, they squinted or blinked again – a measurable sign of emotional response.

At the same time, their brain activity showed a two-phase pattern: a brief initial burst followed by a slower, longer-lasting phase linked to emotional processing.

When the same test was run in mice, the results were strikingly similar. After multiple puffs, the mice showed signs of entering a negative emotional state, avoiding reward-seeking behaviors.

What happens when emotions fade?

Next, the researchers tested whether they could disrupt this emotional state. They used ketamine, a medication approved at low doses for treating depression. Ketamine is known for causing dissociation – a state where people feel detached from their emotions.

“Ketamine recipients are fully aware of sensory experience, but they often don’t have typical emotions about that experience,” said Dr. Deisseroth. “It’s as if it’s happening to someone or something else.”

After giving a single dose of ketamine to the participants, the researchers saw a dramatic change. The subjects still reflexively blinked at each air puff, but they stopped squinting afterward.

When asked about the puffs, their responses were telling: “The air puff . . . felt entertaining,” said one participant. “It felt like little whispers on my eyeballs,” said another.

In both humans and mice, ketamine sped up the second, slower phase of brain activity. It made the emotional response fade more quickly, like lifting a piano’s sustain pedal to stop the note.

Brain timing shapes our emotions

The results suggest that the second phase of brain activity – the slower, lingering wave – is closely tied to emotional states. Speeding it up, as ketamine does, cuts the emotion short.

In fact, the team found that even without air puffs, ketamine shortened the brain’s “intrinsic time scale” – the natural rhythm of how long brain activity patterns persist.

Dissociation, they found, may work by making emotional signals too brief to be properly integrated across the brain.

“Dissociative medication may render the stabilizing phase of brain activity so ephemeral that information can’t be properly integrated across the brain, including to build an emotional state,” explained Dr. Deisseroth.

What it means for mental health

Could tweaking the brain’s timing help treat mental illnesses? “Far too-brisk decay of that integrative brain activity could generally prevent coordination of information flowing in from diverse regions of the brain,” noted Dr. Deisseroth.

This could lead to symptoms like those seen in schizophrenia, where individuals sometimes feel disconnected from their own actions.

On the other hand, if brain activity lingers too long, it could result in persistent emotions or intrusive thoughts, as seen in post-traumatic stress disorder, obsessive-compulsive disorder, or depression.

Implications for autism patients

The study raises other interesting possibilities. Could an overly persistent brain state contribute to the processing difficulties seen in autism?

“People with autism spectrum disorder are often known to have trouble keeping up with high-speed bursts of information,” said Dr. Deisseroth.

“These are fascinating possibilities, which we are now exploring. It’s amazing what an unbiased brainwide screen can reveal, especially with the right technology and across millions of years of evolution.”

The study is part of Stanford Medicine’s Human Neural Circuitry research program, which was founded by Dr. Deisseroth. The program focuses on understanding how the brain works in both health and disease by combining cutting-edge technologies for measuring brain activity and behavior.

The findings are published in the journal Science.

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