No group-level changes in corticospinal excitability following low-intensity theta-burst ultrasound stimulation of the primary motor hand area
J Laugesen, S Bertino, MM Beck, B Sigurðsson, A Thielscher, L Christiansen, HR Siebner
2026 · 10.64898/2026.01.06.697894
Abstract
Background Low-intensity transcranial ultrasound stimulation (TUS) is a novel non-invasive brain-stimulation technique offering high spatial precision and depth penetrance. Theta burst TUS (tbTUS), featuring a temporal theta burst stimulation pattern, has been reported to facilitate corticomotor excitability, when applied to the human primary motor hand area (M1-HAND). However, replication attempts have yielded inconsistent results. Methods Fifteen healthy human participants underwent neuronavigated tbTUS targeting the left M1-HAND in the anterior wall of the precentral sulcus, as well as anterior and posterior active control sites. The three tbTUS conditions were applied in counterbalanced order on separate days. Corticospinal excitability was assessed via motor evoked potentials (MEPs) recorded before and 5, 15, 30, and 60 minutes after tbTUS, and analyzed using an rmANOVA. Results None of the tbTUS conditions produced consistent group-level changes in MEP amplitude at any time point. Both intra- and inter-subject variability were high, and individual MEP changes following precentral tbTUS did not correlate with changes after control-site stimulation. Conclusions We did not observe reliable modulatory effects of neuronavigated tbTUS on corticospinal excitability. Methodological and hardware differences may account for discrepancies across studies. Our findings align with recent reports questioning the robustness of tbTUS-induced facilitation.
Abstract via europepmc.
Exposures
Exposure 1: tbTUS of left M1-HAND (anterior wall of precentral sulcus); anterior and posterior sites 3 cm away served as active controls
Target: primary motor cortex — “left M1-HAND in the anterior wall of the precentral sulcus”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500 four-element transducer with TPO-203 ✓
| Waveform | theta burst | |
|---|---|---|
| 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) | 540 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 9.1 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | 0.91 | ✓✓✓ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 330 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Theta burst TUS after Zeng et al. (2022): burst length 20 ms, period 200 ms, duty cycle 10%, duration 80 s. Free-field output was measured with a 10 ms pulse and 10 ms interval (100% duty cycle) at 9.10 W/cm2 Isppa.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Stated as a 200 ms period; converted to 5 Hz.exposures[0].free_field.pressure_kpa— 0.54 MPa is a free-field value from the TUS calculator simulation, not a hydrophone measurement.exposures[0].in_situ.pressure_kpa— Derated with the TUS calculator assuming 5.8 mm scalp, 10 mm skull and 1.565 dB/cm/MHz; no individual skull modelling.exposures[0].free_field.isppa_w_cm2— Hydrophone measurement of the 9.10 W/cm2 Isppa used a 10 ms pulse and 100% duty cycle rather than the 20 ms/10% protocol.exposures[0].device.family— Table 2 gives the manufacturer as Sonic Concepts, Neurofus LT; CTX-500 with TPO-203 recorded as neurofus.sham_type— No sham arm; two active control sites 3 cm anterior and posterior to the verum target.blinding— Experimenters could not see post-tbTUS MEPs; blinding of participants not stated.