Noninvasive Suppression of Responses to Threat Using Focused Ultrasonic Waves
Keisuke Tsunoda, Taylor D. Webb, Carter Lybbert, Matthew G. Wilson, Brian J. Mickey, Jan Kubanek
The Journal of Neuroscience 2026 · 10.1523/jneurosci.0776-25.2025
Abstract
The processing of threat- and fear-related responses is known to involve the amygdala and the bed nucleus of the stria terminalis. Malignant activity in these nuclei is associated with several important disorders, including generalized anxiety disorder and post-traumatic stress disorder. A noninvasive approach to modulate these deep brain circuits could provide novel treatment options for these disorders, but current noninvasive approaches cannot access these targets directly. This study modulates these nuclei using transcranial low-intensity focused ultrasound in nonhuman primates. The ultrasound was delivered into these circuits prior to an emotional stimulus (neutral, submissive, or threatening monkey faces or snake images) while measuring the system's autonomic response using pupil size. We found that the neuromodulation substantially reduced the pupillary responses to threat images. The effect was specific to threat face images and specific to focused ultrasound; it was not observed for other types of images or for unfocused or no-ultrasound. Thus, focused ultrasound targeting fear circuits can suppress responses to threat images. This approach could be developed into noninvasive treatments of disorders that affect these circuits.
Abstract via europepmc.
Exposures
Exposure 1: Focused ultrasound, amygdala (bilateral)
Target: amygdala — “bilateral amygdala”
Device: other named manufacturer · Doppler Electronic Technologies · HP-500K-256-BE ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 480 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 6.67 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 20.01%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 340 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 3.69 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.18 | ✓✓✓ |
Stimulation was applied sequentially to the four targets (left and right amygdala, left and right BNST) in a repeating cycle, with each stimulation period lasting 30 ms followed by a 120 ms interval before the next target. Each target was thus sonicated for 30 ms every 600 ms, repeated over 30 s, delivered before image presentation in each trial block; sessions interleaved with a visual discrimination task.
Exposure 2: Focused ultrasound, BNST (bilateral)
Target: other — “bilateral BNST (bed nucleus of the stria terminalis)”
Device: other named manufacturer · Doppler Electronic Technologies · HP-500K-256-BE ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 480 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 6.67 | ✓✓✓⚑ |
| Duty cycle (%) | 5pulse duration × PRF gives 20.01%, which disagrees with the stated value | ✓✓✓⚑ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 680 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 14.84 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.74 | ✓✓✓ |
Stimulation was applied sequentially to the four targets (left and right amygdala, left and right BNST) in a repeating cycle, with each stimulation period lasting 30 ms followed by a 120 ms interval before the next target. Each target was thus sonicated for 30 ms every 600 ms, repeated over 30 s, delivered before image presentation in each trial block; sessions interleaved with a visual discrimination task.
Flags from extraction
exposures[0].in_situ.pressure_kpa— Pressures are estimates from MR thermometry, Pennes bioheat and a simple array simulation that ignores the skull; method set to simulation as the nearest vocabulary term. The paper calls them informed estimates, not absolute measurements.exposures[1].timing.duty_cycle_pct— BNST duty cycle is garbled by OCR in the Methods sentence ('D C = 5 9 6'); 5 taken from the Discussion sentence on the 5 % duty cycle.exposures[1].timing.pulse_repetition_frequency_hz— BNST PRF is OCR-garbled; the quoted sentence is the amygdala one giving 6.67 Hz, the BNST sentence reads 'PRF = 6.67 Hz' in garbled form.exposures[0].timing.protocol_description— Four targets are sonicated in an interleaved cycle (30 ms each every 600 ms, 30 s total); each target's PRF is 6.67 Hz. The two targets are listed as separate exposures although delivered within the same sonication.n_sessions_per_subject— 8-11 sessions per condition; 30 and 33 sessions were collected in total across conditions for the two monkeys.exposures[0].device.family— Transducer maker Doppler Electronic Technologies is not in the family list; drive system was a Verasonics Vantage 256.