Ultrasound neuromodulation reveals distinct roles of the dorsal anterior cingulate cortex and anterior insula in learning
Nomiki Koutsoumpari, Johannes Algermissen, Siti Nurbaya Yaakub, Hanneke EM den Ouden, Nadege Bault, Elsa Fouragnan
PLOS Biology 2026 · 10.1371/journal.pbio.3003767
Abstract
Pavlovian biases reflect how evolutionarily hard-wired tendencies-automatic approach toward reward cues and withdrawal from threat cues-can interfere with flexible, goal-directed action. Such biases arise through three mechanisms: (a) anticipated rewards energize action while anticipated punishments suppress it (response bias), (b) agents learn differently from actions than from inactions (learning bias), and (c) reward/punishment cues themselves drive repetitive behavior, independent of outcomes (perseveration bias). The neural origin of these biases is unclear. Past evidence suggests dorsal anterior cingulate cortex (dACC) and anterior insula (aIns) as part of a "reset network" that rapidly responds to salient information and might contribute to these biases. We used transcranial ultrasonic stimulation (TUS) in 29 healthy participants to interfere with neural activity in these regions and test their causal role in a within-subject, counter-balanced design across three sessions (sham, TUS-dACC, TUS-aIns). Computational modeling revealed a functional differentiation of both regions in Pavlovian biases: while TUS to either region did not affect the response bias, TUS to the aIns decreased people's learning bias, while TUS to dACC increased participants' perseveration bias. Although the dACC and aIns are part of the same network and often co-activate during decision-making tasks, TUS interference reveals their distinct roles: the dACC mediates cue-dependent persistence while the aIns is critical for inferring whether outcomes are self-caused.
Abstract via europepmc.
Exposures
Exposure 1: TUS-dACC
Target: dorsal anterior cingulate cortex — “dorsal anterior cingulate cortex”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500 NeuroFUS TPO, 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) | 50 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 450 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 6.69 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
5 Hz-patterned protocol with a 10% duty cycle (500 kHz, 20 ms pulses, pulsed every 200 ms), applied for 80 s (400 pulses in total), delivered to the left then the right hemisphere for the bilateral aIns; the Go/NoGo task started within 10 min of the end of sonication.
Exposure 2: TUS-aIns (bilateral anterior insula)
Target: anterior insula — “bilateral anterior insula”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500 NeuroFUS TPO, 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) | 50 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 470, 480swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 7.6, 7.53swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
5 Hz-patterned protocol with a 10% duty cycle (500 kHz, 20 ms pulses, pulsed every 200 ms), applied for 80 s (400 pulses in total), delivered to the left then the right hemisphere for the bilateral aIns; the Go/NoGo task started within 10 min of the end of sonication.
Flags from extraction
exposures[1].in_situ.pressure_kpa— Table 1 gives separate left (0.47 MPa, 7.60 W/cm2) and right (0.48 MPa, 7.53 W/cm2) aIns target-ROI means; the left values are recorded.exposures[0].in_situ.pressure_kpa— Simulated mean across 29 participants in a 10 mm radius target ROI (Table 1); the table gives MPa and W/cm2.exposures[0].free_field.isppa_w_cm2— Also stated as approximately 50 W/cm2 in water; a supplementary figure mentions simulations at 30 W/cm2, not recorded.blinding— Described as single-blinded; sham sound mimicked the TUS pulse repetition rate through bone-conduction headphones.