Summary: Emotions steer our behavior, but when they are mistimed or persist too long they can contribute to psychiatric illness. In a landmark study, researchers mapped brain-wide activity evoked by a mildly aversive but medically safe sensory stimulus—brief air puffs to the eye—in both human patients and mice.
They identified a consistent two-phase neural response: an immediate, fast broadcast of the sensory event followed by a slower, persistent activity pattern that correlates with emotional processing. The antidepressant and dissociative agent ketamine selectively reduced that slower phase, blunting emotional impact while leaving immediate sensory signaling intact. These findings suggest that the timing and persistence of brainwide signals help shape emotional states, and that disruptions in those dynamics could underlie many neuropsychiatric conditions.
Key Facts:
- Two-phase response: A brief, fast broadcast of sensory information is followed by a longer-lasting, distributed signal associated with emotion.
- Ketamine effect: Ketamine selectively shortens the slower phase and reduces synchronization across networks, diminishing the formation of a negative emotional state without blocking basic sensation.
- Cross-species conservation: Humans and mice display highly similar activity patterns, indicating conserved mammalian circuitry for converting sensory input into emotional states.
Source: Stanford
Emotions organize behavior, but when they are misplaced or prolonged they can cause severe problems.
Despite advances in neuroscience and psychiatry, the neural processes that transform brief sensory events into persistent emotional states remain poorly understood. To address this gap, Stanford Medicine investigators combined high-resolution brain recordings with precisely timed sensory stimulation to reveal conserved dynamic principles of emotional emergence.
Published May 29 in Science, the study used brief, precisely timed corneal air puffs—an ophthalmology tool that is safe but slightly unpleasant—to evoke reflexive and affective responses in both humans and mice. The experiments combined intracranial recordings in hospitalized human patients and dense single-unit probes in mice to screen brainwide activity with millisecond precision.
Because mice and humans diverged from a common ancestor roughly 70 million years ago, identifying neural dynamics that appear in both species highlights principles likely conserved across mammals. The results clarify how sensory input is transformed into an emotional signal that can persist, generalize, and alter behavior.
Integrating signals across a large brain
Karl Deisseroth and colleagues emphasize that mammalian brains evolved at large size to enable richer, more complex mental life. But larger brains impose timing constraints: signals must travel, converge and be integrated across widespread regions before a cohesive decision or emotional state can form. Emotions may therefore depend on a brief window of sustained brainwide communication that allows integration of sensory data, goals, body state and context.
The investigators liken this integrative window to a piano sustain pedal: it extends the influence of a brief sensory note so the brain can combine diverse inputs. If the duration of that sustained activity is too short or too long, emotional processing could be impaired.
Experimental approach: matched human and mouse screens
Instead of altering neural circuits directly with optogenetics, the team used a cross-species screening strategy. They administered the same precisely timed, measurable stimulus to humans and mice and recorded brainwide responses using techniques appropriate to each species. This allowed them to focus on dynamics conserved across evolution rather than species-specific signals.
Human participants were patients undergoing intracranial monitoring for epilepsy, which provided clinical indications for implanted electrodes and a rare opportunity to record deep and distributed brain signals during controlled sensory stimulation. Subjects described the air puffs as “annoying,” “unpleasant” or “uncomfortable,” and repeated puffs led to an accumulating, lingering state of irritation—an emotional response lasting beyond the stimulus series.
Behaviorally, each puff produced an immediate, reflexive blink followed by seconds of additional eye squinting or guarded closure. Those measurable post-puff behaviors provided a precise, comparable index of emotion-related responses in both species.
Simultaneous recordings revealed a biphasic neural pattern: a rapid, roughly 200-millisecond global broadcast of the puff signal across the brain, followed by a slower, approximately 700-millisecond persistent phase concentrated in emotion-related circuits. This second phase created an extended interval for brainwide integration consistent with emotional processing.
When they repeated the experiment in mice, the researchers observed the same two-phase pattern. Repeated puff sequences produced an accumulating second-phase signal and a sustained negative state in mice, evidenced by reduced reward-seeking—behavioral features typical of emotion.
Ketamine selectively shortens the emotional window
To test whether the persistent second phase was necessary for emotional formation, the team administered low-dose ketamine, an FDA-approved antidepressant known to produce transient dissociation. People under ketamine remain aware of sensations but often lack normal emotional responses.
After ketamine, participants still perceived the puffs and showed intact reflexive blinks, but they no longer displayed the prolonged eye closure or self-protective behavior. Mice showed the same selective behavioral change. Neural data matched these observations: the initial fast sensory broadcast remained intact, but the slower, persistent phase decayed faster under ketamine, narrowing the integration window.
Ketamine also accelerated intrinsic timescales of spontaneous neural activity and reduced brainwide synchrony in networks engaged by the puffs. Both species recovered normal timing as the drug effect wore off, and control experiments using neutral stimuli revealed that ketamine’s sharpening of response dynamics generalizes beyond aversive inputs.
Implications for psychiatric disorders
These results point to signal persistence and timing as fundamental properties that shape emotional states. If intrinsic timescales are too short, information from diverse brain regions cannot be coordinated, which may produce dissociation-like symptoms or impair integrated behavior. If timescales are too long, brain states may become hyperstable, producing persistent or untimely emotions and intrusive thoughts as seen in PTSD, OCD, depression and some eating disorders. Variations in timing across specific circuits could therefore underlie different symptom profiles.
Beyond emotion, altered signal persistence could affect information-processing speed across individuals and conditions—for example, the difficulty some people with autism spectrum disorder have in following rapidly changing input.
The authors conclude that conserved, tunable timing properties—an intrinsic “sustain” for brainwide signals—help convert brief sensory events into lasting emotional states. Modulating that timescale may have diagnostic and therapeutic implications for neuropsychiatric disorders.
Stanford University’s Office of Technology Licensing has filed a patent relating to methods described in the study. Additional contributors include researchers from the Veterans Affairs Palo Alto Health Care System and Weill Cornell Medicine.
Funding: Supported by the National Institutes of Health (grants P50DA042012, R01MH105461, R01MH133553 and R01NS095985), the AE Foundation and anonymous donors.
About this emotion and neuroscience research news
Author: Bruce Goldman
Source: Stanford
Contact: Bruce Goldman – Stanford
Image: The image is credited to Neuroscience News
Original Research: Closed access. “Conserved brain-wide emergence of emotional response from sensory experience in humans and mice” by Karl Deisseroth et al. Science
Abstract
Conserved brain-wide emergence of emotional response from sensory experience in humans and mice
INTRODUCTION
Emotional states are central to both healthy and disordered human life, yet the neural mechanisms that translate brief sensory events into lasting emotions are not well understood. In mammals, persistent emotional responses may function to integrate external and internal information spread across distributed brain regions to guide appropriate behaviors.
RATIONALE
To identify broadly conserved neural dynamics, the researchers performed unbiased brainwide activity screens in humans and mice performing the same task. They combined high-speed behavioral measures, clinically compatible pharmacological manipulation, and deep, brain-spanning electrophysiological recordings to investigate principles that generalize across species.
RESULTS
Corneal air-puff sequences produced fast reflexive and sustained affective eye-closure behaviors in both species. The sustained response carried negative valence, persisted beyond stimulation, generalized across contexts, and could be abolished by ketamine. Brainwide recordings revealed a biphasic process: a rapid global sensory broadcast followed by a slower, persistent signal distributed across emotion-related circuits. Ketamine selectively shortened the persistent phase while leaving the fast broadcast intact, blocking the emergence of the emotional state. The dynamics fit first-order system behavior, with drug effects modeled by changes in a single decay timescale. Ketamine also shortened intrinsic baseline timescales and reduced cross-brain synchrony in networks tied to persistent responses.
CONCLUSION
Mammalian emotional states appear to arise through conserved persistent activity dynamics that act as a distributed neural context for integration. These dynamics are governed by a tunable intrinsic timescale—analogous to a sustain pedal—that shapes whether brief sensory events become lasting emotional states. Alterations in these timing properties may underlie and inform treatment approaches for various neuropsychiatric disorders.