Study reveals how negative sensory experiences trigger lasting emotions in humans and mice akin to a "piano sustain pedal"

Amazing stuff! Now you know what these scientists do in their spare time! 😊

"... Neuroscientists and psychiatrists, despite their best efforts, don’t understand nearly enough about the brain activity underlying our emotions, how they make us tick, and how they can make us sick.

Now, in a study ... investigators have mapped the brainwide neuronal processing that underlies the emotional response triggered by a mildly unpleasant sensory experience. Features of this brain activity turn out to be shared by humans and mice ...

The findings could help unveil some of the driving forces behind numerous neuropsychiatric disorders, which are characterized in large part by troublesome emotional manifestations. ..."

From the abstract of the Perspective:

"... Whether fleeting or lasting, emotions influence perceptions, behavior, and decisions well beyond the experience that set them in motion. Yet very little is known about how the brain holds onto these internal states. Explaining the biological basis of their enduring nature is crucial for building a mechanistic understanding of emotion. ... Kauvar et al. (1) report an evolutionarily conserved brainwide response to an emotional stimulus that serves as the early-stage neural substrate of an emotion state. Thus, they identify a fundamental process that may help explain how emotions emerge."

From the editor's summary and abstract:

"Editor’s summary

Many animal species have been shown to display distinct emotional states. However, little is known about the neuronal mechanisms underlying the emergence of emotional responses to discrete events. Kauvar et al. performed parallel behavioral, pharmacological, and electrophysiological experiments in mice and humans and identified evolutionarily conserved brain signals forming a basis of sensory and emotional processing of salient aversive stimuli ... After stimulus-specific (sensory) information is rapidly disseminated throughout the mammalian brain, a slower and more persistent (emotional) activation of brainwide networks occurs. These translational results enhance our understanding of the neural substrates of affective states across species. ...

Structured Abstract

...

RATIONALE

To identify broadly conserved patterns of neural activity, we first developed unbiased brain-wide activity screens spanning widely divergent mammalian species. Specifically, we explored when, where, and how emotional states emerge, using high-speed, invasive, and global methods in human and mouse subjects carrying out the same task. While recognizing and leveraging the value of obtaining verbal descriptions of subjective emotional experience from human subjects for this question, we also explicitly bridged human and mouse systems with temporally precise affective behavioral measures, clinically compatible pharmacological interventions, and deep brain-spanning intracranial electrophysiological readouts, designed to be similarly carried out in parallel in both human and mouse subjects, to investigate conserved principles underlying the emergence of lasting emotional states from brief sensory input.

RESULTS

We determined that sequences of air puffs, directed at the cornea of human or mouse subjects, elicit both fast/reflexive and sustained/affective eye closure behaviors; the latter (in both species) is characterized by negative valence, persistence, generalization, and ablation by the dissociative agent ketamine. We performed a brain-wide neural activity screen of this temporally precise behavioral response, using intracranial stereo-electroencephalography (iEEG) in humans and multiprobe Neuropixels single-unit electrophysiology in mice. This brain-wide screen revealed a biphasic process in which emotionally salient sensory signals are swiftly broadcast throughout the mammalian brain and directly followed by a slower and widely distributed persistent signal.

We discovered that the persistent signal could be selectively and similarly blocked by ketamine while preserving the fast sensory broadcast in both species, and that emergence of a behaviorally defined emotional state could be selectively blocked by this intervention.

We found that the accumulation and decay pattern of persistent population neural activity was consistent with first-order system dynamics, and that the dose-dependent pharmacological impact on the emotional response could be well-modeled by varying a single decay timescale parameter, with emotion-blunting dissociative drugs accelerating the decay.

We furthermore found (in both humans and mice) that ketamine accelerated the intrinsic timescale of baseline spontaneous activity and reduced brain-wide population coupling in networks with puff-triggered persistent activity.

Control experiments in mice with a neutral auditory stimulus (while operating on faster timescales than emotionally salient stimuli) revealed that the pharmacological effect of sharpening response dynamics and reducing capacity to maintain persistent information across the brain was generalizable, highlighting the importance of signal persistence in the establishment of brain-wide responses.

CONCLUSION

We find that mammalian emotional states, in a conserved pattern spanning divergent species, are integrated from sensory experiences through persistent activity dynamics that can be shaped by a global and tunable intrinsic timescale, akin to the action of a piano sustain pedal. Functioning as a distributed neural context, adaptive emotional states appear to depend upon brain-wide mechanisms of signal persistence in specific networks.

Furthermore, consistent with our measurements of intrinsic timescale modulation by clinically relevant intervention, aspects of the etiology and treatment of certain neuropsychiatric disorders may be governed by altered stability of brain states linked to maladaptively fast or slow intrinsic timescales."

Study reveals how sensory experiences trigger lasting emotions | Stanford Report "Scientists found that humans and mice share persistent brain-activity patterns in response to negative sensory inputs – offering insight into emotion and potential links to neuropsychiatric disorders."

A wave of emotion (no public access) "Sustained brainwide patterns of activity enable emotions to outlast their triggers"

Conserved brain-wide emergence of emotional response from sensory experience in humans and mice (no public access)

Brain-wide emergence of emotional response in humans and mice.