Optimized ultrasound neurostimulation of ventromedial prefrontal cortex reverses depression behaviours and normalizes brain metabolism
Marc Legrand, Laurent Galineau, Anthony Novell, Barbara Planchez, Bruno Brizard, Samuel Leman, Clovis Tauber, Jean-Michel Escoffre, Sophie Serriere, Tarik Iazourene, Wissam El-Hage, Patrick Emond, Catherine Belzung, Ayache Bouakaz
npj Acoustics 2026, 2 · 10.1038/s44384-026-00050-z
Exposures
Exposure 1: Single-pulse pressure-response mapping at primary motor cortex (M1)
Target: primary motor cortex — “M1 (primary motor cortex)”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 160 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.1 | ✓✓✓ |
| Duty cycle (%) | 1.6pulse duration × PRF gives 1.6% | ✓✓✓⚑ |
| Sonication duration (s) | 0.16 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingmean or range across subjects | |
| In-situ pressure (kPa) | 50, 500swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 5.33 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.085 | ✓✓✓ |
Single continuous 160 ms pulses delivered to left M1 at pressures stepped from 50 to 500 kPa in 50 kPa increments, ten pulses per step, repeated every 10 s (0.1 Hz); this inter-pulse repetition corresponds to a stated 1.6% duty cycle across the pulse train (distinct from the internal waveform, which is a single continuous burst per pulse). Motor success (visible forepaw twitch, n=20) and motor-evoked potential amplitude (EMG, n=10) were used to derive a motor threshold of 250 kPa and an optimal plateau at 400 kPa.
Exposure 2: Repeated-pulse USNS of the infralimbic cortex (IL)
Target: ventromedial prefrontal cortex — “infralimbic cortex (IL), rodent homologue of vmPFC”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 160 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.1 | ✓✓✓ |
| Duty cycle (%) | 1.6pulse duration × PRF gives 1.6% | ✓✓✓ |
| Sonication duration (s) | 600 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 400 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 5.33 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.085 | ✓✓✓ |
60 single 160 ms pulses at 400 kPa delivered at 0.1 Hz (every 10 s) over a 10 min session. For focality confirmation (c-Fos), one such session was given to 4 active mice (vs 4 sham-anaesthesia mice); for the chronic UCMS experiment, one session per day was repeated for 5 consecutive days (days 29-33), targeted stereotaxically at bregma +2.0 mm, midline.
Flags from extraction
n_subjects— Given as group-size list per instructions rather than summed: 30 mice for parameter-setting (M1 motor screening n=20 plus EMG n=10, a subset of which were later reused for the 8-mouse IL c-Fos focality experiment), and 15 mice in the chronic IL-USNS treatment arm of the UCMS cohort; other UCMS arms (sham-USNS, vehicle, fluoxetine, non-stressed) did not receive ultrasound.sham_type— 'Sham-USNS'/'sham controls' are described only as anaesthesia without ultrasound; the paper does not state whether a transducer was placed but powered off or simply absent, so the sham mechanism is not fully described.exposures[0].timing.duty_cycle_pct— Text states 'duty cycle 1.6%' for the repeated 160 ms pulses at 0.1 Hz, but this describes the inter-pulse repetition duty cycle across a pulse train, not the internal pulse waveform (which is a single continuous burst); left null per the continuous-wave rule and described in protocol_description instead.n_sessions_per_subject— Varies by experiment: single session for M1 optimisation and the 8-mouse c-Fos focality test, versus 5 consecutive daily sessions for the chronic UCMS IL-USNS group.exposures[0].timing.waveform— set to pulsed by the tie-break: the ruled timing has a pulse repetition or duty cycleexposures[1].timing.waveform— set to pulsed by the tie-break: the ruled timing has a pulse repetition or duty cycle