Non-invasive ultrasonic neuromodulation of the human nucleus accumbens impacts reward sensitivity
Siti N. Yaakub, John Eraifej, Nadège Bault, Mathilde Lojkiewiez, Elouan Bellec, Jamie Roberts, Noah S. Philip, Amir Puyan Divanbeighi Zand, Alexander L. Green, Matthew F. S. Rushworth, Elsa F. Fouragnan
Nature Communications 2025 · 10.1038/s41467-025-65080-9
Abstract
Precisely neuromodulating deep brain regions could bring transformative advancements in both neuroscience and treatment. We demonstrate that non-invasive transcranial ultrasound stimulation (TUS) can selectively modulate deep brain activity and affect learning and decision making, comparable to deep brain stimulation (DBS). We tested whether TUS could causally influence neural and behavioural responses by targeting the nucleus accumbens (NAcc) using a reinforcement learning task. Twenty-six healthy adults completed a within-subject TUS-fMRI experiment with three conditions: TUS to the NAcc, dorsal anterior cingulate cortex (dACC), or Sham. After TUS, participants performed a probabilistic learning task during fMRI. TUS-NAcc altered BOLD responses to reward expectation in the NAcc and surrounding areas. It also affected reward-related behaviours, including win-stay strategy use, learning rate following rewards, learning curves, and repetition rates of rewarded choices. DBS-NAcc perturbed the same features, confirming target engagement. These findings establish TUS as a viable approach for non-invasive deep-brain neuromodulation.
Abstract via europepmc.
Exposures
Exposure 1: TUS-NAcc
Target: nucleus accumbens — “left nucleus accumbens (TUS-NAcc)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · bespoke CTX-500 NeuroFUS TPO system, four-element annular transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓⚑ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 35 | ✓✓✓⚑ |
| 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 |
80 s of 5 Hz repetitive TUS (20 ms pulses, 200 ms pulse repetition interval, 400 pulses), delivered offline before an fMRI session with a reversal learning task.
Exposure 2: TUS-dACC
Target: dorsal anterior cingulate cortex — “left dorsal anterior cingulate cortex (TUS-dACC)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · bespoke CTX-500 NeuroFUS TPO system, four-element annular transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 35 | ✓✓✓ |
| 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 |
80 s of 5 Hz repetitive TUS (20 ms pulses, 200 ms pulse repetition interval, 400 pulses), delivered offline before an fMRI session with a reversal learning task.
Flags from extraction
n_sessions_per_subject— Four visits include one screening/MRI visit with no sonication; three visits had TUS-NAcc, TUS-dACC or Sham.exposures[0].free_field.isppa_w_cm2— 35 W/cm2 is the free-field Isppa kept constant; in situ values were simulated per participant but only appear in the supplement and Fig 1f.sham_type— Sham had the TPO turned off with the transducer placed to target the medial frontal cortex, plus bone-conducted sound mimicking the protocol; dACC TUS served as an active control site.adverse_events— Authors report no difference between TUS and Sham; non-TUS symptoms (sleepiness, neck pain, headache, blurry vision) attributed to MRI.exposures[0].timing.pulse_repetition_frequency_hz— Text gives 5 Hz PRF and a 200 ms pulse repetition interval.
Notes: The paper also reports three DBS-NAcc patients (no ultrasound); not counted in n_subjects.