The human amygdala in threat learning and extinction

Science Advances, vol. 12, pp. eaea8233

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.

Authors 7

1. Sjoerd W. Meijer corresponding

   Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

2. Eleonora Carpino

   University of Oxford · Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour · University of Plymouth

   Affiliation as printed

   Brain Research and Imaging Centre, Faculty of Health, University of Plymouth, Plymouth, UK

   Department of Experimental Psychology, University of Oxford, Oxford, UK

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

   School of Psychology, Faculty of Health, University of Plymouth, Plymouth, UK

3. Benjamin R. Kop

   Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

4. Jesse Lam

   Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

5. Lycia D. de Voogd Aachen Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition

   Leiden University · Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Behavioral Science Institute (BSI), Radboud University, Nijmegen, Netherlands

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

   Institute of Psychology, Leiden University, Leiden, Netherlands

   Leiden Institute for Brain and Cognition, Leiden University, Leiden, Netherlands

6. Karin Roelofs corresponding

   Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Behavioral Science Institute (BSI), Radboud University, Nijmegen, Netherlands

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

7. Lennart Verhagen corresponding

   Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands