Dissociation and the Speed of Emotion
To prove that the second, slower phase of brain activity was the key to the emotional state, the team used a pharmacological intervention: ketamine.
In clinical settings, low doses of ketamine are known to cause dissociation. "Ketamine recipients are fully aware of sensory experience, but they often don’t have typical emotions about that experience," Deisseroth explained. "It’s as if it’s happening to someone or something else."
Under the influence of ketamine, the human participants reported that the air puffs no longer bothered them. One participant described the sensation as "entertaining," while another said it felt like "little whispers on my eyeballs."
The behavioral data backed up these subjective reports. While the reflexive first-phase blink remained intact, the self-protective second-phase squinting disappeared. The brain still received the "news" of the puff, but the emotional "sustain" was gone.
In both humans and mice, ketamine selectively accelerated the decay of the second phase of brain activity. It effectively "released the sustain pedal," preventing the brain from integrating the sensory information into a lasting emotional state. Furthermore, the team found that ketamine reduced overall brain synchrony and accelerated the brain’s "intrinsic time scale"—the rate at which activity patterns correlate—even when no stimulus was present.
A New Framework for Neuropsychiatry
The discovery that emotional states are tied to the timing and persistence of brainwide signals opens a new door for psychiatric medicine. Deisseroth suggests that many disorders could be categorized by how they affect these timing properties.
If the decay of integrative brain activity is too fast—as seen with ketamine—the brain may struggle to coordinate information, leading to the "alien" perceptions or lack of self-agency associated with schizophrenia.
Conversely, if the second wave of activity decays too slowly or becomes hyper-stabilized, it could result in the intrusive thoughts and persistent negative emotions characteristic of PTSD, obsessive-compulsive disorder, or clinical depression. In these cases, the brain’s "sustain pedal" may be stuck, keeping the individual trapped in a specific emotional state long after the triggering event has passed.
The researchers also see implications for autism spectrum disorder. "People with autism spectrum disorder are often known to have trouble keeping up with high-speed bursts of information," Deisseroth said. It is possible that a hyper-stabilized brain state makes it difficult for the brain to reset and follow rapidly changing social or linguistic inputs.
By shifting the focus from "where" things happen in the brain to "how long" they persist, the Stanford team has introduced a temporal dimension to our understanding of mental health.
"These are fascinating possibilities, which we are now exploring," Deisseroth said. "It’s amazing what an unbiased brainwide screen can reveal, especially with the right technology and across millions of years of evolution."
The research was supported by the National Institutes of Health, the AE Foundation, and private donors. Stanford University’s Office of Technology Licensing has filed a patent for intellectual property related to the study’s findings.
