Delay- and Pressure-Dependent Neuromodulatory Effects of Transcranial Ultrasound Stimulation
Cyril Atkinson-Clement, Mohammad Alkhawashki, Marilyn Gatica, Stefanos Alexandros Kontogouris, Marcus Kaiser
Neuromodulation: Technology at the Neural Interface 2025, 28, 444-454 · 10.1016/j.neurom.2025.01.004
Abstract
Objective Despite the growing interest in transcranial focused ultrasound stimulation (TUS), our understanding of its underlying mechanisms remains limited. In this study, we aimed to investigate the effects of TUS on several functional magnetic resonance imaging metrics by considering their latency, duration, and relationship with applied acoustic pressure. Materials and methods We recruited 22 healthy volunteers and used a pre- vs post-TUS protocol. Half of the volunteers were stimulated in the right inferior frontal cortex and the other half in the right thalamus. The fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, local functional connectivity density, and eigenvector centrality were considered. These metrics were compared before TUS and at three different time points in the first hour after TUS. Results Our results showed that 1) TUS primarily alters functional connectivity metrics at both the local and global levels; 2) stronger alterations are observed when the delay after TUS increases and 3) when the applied acoustic pressure is close to the maximum. Conclusion These results suggest that some consequences of TUS might not be immediate, inviting us to revise the premise that TUS consequences are immediate and will progressively disappear.
Abstract via europepmc.
Exposures
Exposure 1: IFC-TUS
Target: inferior frontal gyrus — “right inferior frontal cortex (IFC)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS PRO TPO-203 with CTX-500-4CH transducer ✓
| 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) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | ⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 153.5 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.0833 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 54.51 | ✓✓✓ |
We used a theta-burst TUS protocol with the following parameters: fundamental frequency 500 kHz, pulse duration 20 ms, pulse repetition interval 200 ms, pulse repetition frequency 5 Hz, duty cycle 10%, spatial-peak pulse-average intensity 54.51 W/cm2, and total duration 80 seconds.
Exposure 2: Thal-TUS
Target: thalamus — “right thalamus”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS PRO TPO-203 with CTX-500-4CH transducer ✓
| 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) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 134.8 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.155 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 54.51 | ✓✓✓ |
We used a theta-burst TUS protocol with the following parameters: fundamental frequency 500 kHz, pulse duration 20 ms, pulse repetition interval 200 ms, pulse repetition frequency 5 Hz, duty cycle 10%, spatial-peak pulse-average intensity 54.51 W/cm2, and total duration 80 seconds.
Flags from extraction
randomised— Paper states participants were 'pseudorandomly assigned' to groups; exact allocation procedure not detailed.exposures[0].free_field.isppa_w_cm2— Domain of the 54.51 W/cm2 spatial-peak pulse-average intensity (device setting) is not explicitly stated as free-field/water vs in situ; assigned to free_field as it is listed as a fixed device parameter separate from the per-subject acoustic simulation results in Table 1.sham_type— Authors explicitly state there is no valid sham model used or available for this TUS study; no control condition was included.