The human amygdala in threat learning and extinction

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.