Dynamic changes in human brain connectivity following ultrasound neuromodulation
Cyril Atkinson-Clement, Mohammad Alkhawashki, Marilyn Gatica, James Ross, Marcus Kaiser
Scientific Reports 2024, 14 · 10.1038/s41598-024-81102-w
Abstract
Non-invasive neuromodulation represents a major opportunity for brain interventions, and transcranial focused ultrasound (FUS) is one of the most promising approaches. However, some challenges prevent the community from fully understanding its outcomes. We aimed to address one of them and unravel the temporal dynamics of FUS effects in humans. Twenty-two healthy volunteers participated in the study. Eleven received FUS in the right inferior frontal cortex while the other 11 were stimulated in the right thalamus. Using a temporal dynamic approach, we compared resting-state fMRI seed-based functional connectivity obtained before and after FUS. We also assessed behavioural changes as measured with a task of reactive motor inhibition. Our findings reveal that the effects of FUS are predominantly time-constrained and spatially distributed in brain regions functionally connected with the directly stimulated area. In addition, mediation analysis highlighted that FUS applied in the right inferior cortex was associated with behavioural alterations which was directly explained by the applied acoustic pressure and the brain functional connectivity change we observed. Our study underscored that the biological effects of FUS are indicative of behavioural changes observed more than an hour following stimulation and are directly related to the applied acoustic pressure.
Abstract via europepmc.
Exposures
Exposure 1: Right inferior frontal cortex (IFC) theta-burst FUS
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 | ✓✓✓⚑ |
Individualised acoustic simulations (using each participant's ZTE-derived skull map) were used to select the transducer trajectory minimising skull thickness to the target; the theta-burst FUS protocol was delivered once, immediately followed by an MRI session (~15 min delay) and a cognitive task (~70 min delay).
Exposure 2: Right thalamus theta-burst FUS
Target: thalamus — “right thalamus (centroid of whole 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 | ✓✓✓ |
Individualised acoustic simulations (using each participant's ZTE-derived skull map) were used to select the transducer trajectory minimising skull thickness to the target; the theta-burst FUS protocol was delivered once, immediately followed by an MRI session (~15 min delay) and a cognitive task (~70 min delay).
Flags from extraction
n_sessions_per_subject— Inferred as one stimulation session (FUS given once, at the second visit); the paper does not state this as an explicit count.exposures[0].timing.pulse_repetition_frequency_hz— PRF was computed from the stated pulse repetition interval (200 ms -> 5 Hz), a period-to-frequency unit conversion rather than independent arithmetic.exposures[0].unspecified_domain.isppa_w_cm2— The device ISPPA setting (54.51 W/cm2) is not stated as free-field or in-situ; placed in unspecified_domain, while the per-target simulated pressure/ISPTA from Table 1 are placed in in_situ.blinding— Paper explicitly compares post- vs pre-FUS sessions 'without a proper placebo (i.e., sham stimulation)'; no blinding procedure is described.