The human amygdala in threat learning and extinction
Sjoerd Meijer, Eleonora Carpino, Benjamin R. Kop, Jesse Lam, Lycia D. de Voogd, Karin Roelofs, Lennart Verhagen
Science Advances 2026 · 10.1126/sciadv.aea8233
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.
Abstract via europepmc.
Exposures
Exposure 1: Amygdala-TUS (experiment I)
Target: basolateral amygdala — “bilateral amygdala”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS Pro (TPO-203-035 / TPO-105-010 with CTX-250-001 / CTX-250-026) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 90 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 45% | ⚑ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 1,240 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 40 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Pulses of 90-ms duration, ramped with a Tukey shape on pressure over 30 ms on/off, repeated at 5 Hz for a total pulse train of 1000 ms, delivered bilaterally and interleaved between the two transducers; TUS began 200 ms before CS onset on each active trial during the 120-trial acquisition phase only.
Exposure 2: Hippocampus-TUS (experiment II)
Target: hippocampus — “posterior hippocampus”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS Pro (TPO-203-035 / TPO-105-010 with CTX-250-001 / CTX-250-026) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 90 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 45% | ⚑ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 1,240 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 40 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Pulses of 90-ms duration, ramped with a Tukey shape on pressure over 30 ms on/off, repeated at 5 Hz for a total pulse train of 1000 ms, delivered bilaterally and interleaved between the two transducers; TUS began 200 ms before CS onset on each active trial during the 120-trial acquisition phase only.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— Text gives 40 W/cm2 in free water; Fig. 2B legend gives Isppa = 38.43 W/cm2 for a single transducer.exposures[0].free_field.pressure_kpa— 1.24 MPa is read from the Fig. 2B legend (single-transducer hydrophone measurement).exposures[0].timing.duty_cycle_pct— Duty cycle not stated in the main text (safety metrics are in table S1, not in the text); bilateral interleaved protocol.exposures[1].free_field.isppa_w_cm2— Text gives 40 W/cm2 in free water; Fig. 2B legend gives Isppa = 38.43 W/cm2 for a single transducer.exposures[1].free_field.pressure_kpa— 1.24 MPa is read from the Fig. 2B legend (single-transducer hydrophone measurement).exposures[1].timing.duty_cycle_pct— Duty cycle not stated in the main text (safety metrics are in table S1, not in the text); bilateral interleaved protocol.n_subjects— 50 analysed (25 per experiment); one participant per experiment was excluded after enrolment (target 26 per experiment), so enrolled count is implied but not stated outright.blinding— Paper says 'partially double-blinded': participants blinded to stimulation and target, investigators blinded to stimulation condition only.sham_type— Sham trials were auditory matching stimulus only, within participant; hippocampus-TUS served as active control site in a separate experiment.