The Ketamine Effect: Releasing the Sustain Pedal
To prove that the second phase of brain activity was indeed the key to the emotional state, the researchers turned to ketamine. At low doses, ketamine is an FDA-approved antidepressant known to cause dissociation—a state where a person is aware of a sensory experience but feels no emotional connection to it.
"Ketamine recipients are fully aware of sensory experience, but they often don’t have typical emotions about that experience," Deisseroth said. "It’s as if it’s happening to someone or something else."
Under carefully controlled clinical conditions, the researchers administered ketamine to the human subjects. The results were striking. The participants still felt the air puffs and still showed the initial reflexive blink, but their subjective sense of annoyance vanished. One participant even described the sensation as "entertaining," while another said it felt like "little whispers on my eyeballs."
Crucially, the brain recordings showed that while the first phase of neural activity (the 200ms "news" broadcast) remained intact, the second phase was dramatically shortened. Ketamine effectively "sped up" the decay of the emotional integration phase. It was as if the drug had released the sustain pedal on the brain’s emotional response. The same effect was observed in mice, who stopped their self-protective squinting but maintained their reflexive blinks.
Toward a New Science of Emotion and Timing
The implications of these findings extend far beyond the laboratory. By identifying that emotional states are dependent on the timing and persistence of brainwide communication, researchers may have found a new way to categorize and treat mental health disorders.
Deisseroth suggests that many neuropsychiatric conditions may be the result of this timing mechanism being "out of tune." For example, if the decay of integrative brain activity is too fast—as seen with ketamine—information cannot be properly integrated. This could explain symptoms in schizophrenia, where patients may perceive their own self-generated actions as being controlled by outside forces.
Conversely, if the second wave of activity is too strong or lasts too long, it could lead to hyperstabilized brain states. This could manifest as the intrusive thoughts of OCD, the persistent despair of depression, or the lingering trauma of PTSD. Even the social and language processing challenges associated with autism might be linked to a brain state that is too "stable" to keep up with the rapid-fire exchange of social information.
"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 study was supported by the National Institutes of Health, the AE Foundation, and anonymous donors. Stanford University’s Office of Technology Licensing has filed a patent for intellectual property related to the study’s findings, signaling a potential shift in how we might one day diagnose and treat the temporal roots of human emotion.
