The human amygdala in threat learning and extinction

TL;DR

This study shows that the human amygdala is crucial for forming lasting threat memories and that targeting it with ultrasound can alter these processes.

Contribution

The study provides causal evidence that the human amygdala is essential for forming threat memories resistant to extinction.

Findings

Amygdala stimulation slowed initial threat acquisition and increased extinction.

Amygdala stimulation modulated memory of threat probability.

TUS offers potential for neuromodulation in disorders involving persistent threat memories.

Abstract

Here, we resolve the long-standing but unconfirmed hypothesis that the human amygdala is essential for rapidly acquiring cued-conditioned threat responses. We provide causal evidence for the amygdala’s contribution to forming threat memories that are resistant to extinction. Using transcranial ultrasound stimulation (TUS), a noninvasive technique that modulates deep brain structures with high spatial and temporal precision, we targeted the bilateral amygdala during Pavlovian threat conditioning in healthy adults. Linear mixed-effects models and computational modeling of trial-level skin conductance responses revealed that amygdala-TUS (experiment I, n = 25), but not hippocampus-TUS (experiment II, n = 25), selectively slowed initial threat acquisition, augmented subsequent extinction, and modulated declarative memory of retrospective threat probability. These findings demonstrate that the human amygdala drives an emotional learning state—learning fast, forgetting slow. Our study shows the potential of TUS for targeted neuromodulation of human deep brain structures implicated in conditions such as posttraumatic stress disorder, where pathological threat memories persist despite therapy.

Ultrasonic neuromodulation of the human amygdala provides causal evidence for its role in forming persistent threat memories.

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