Spatiotemporal Reconfiguration of Functional Brain Networks Following Transcranial Focused Ultrasound Stimulation
Cyril Atkinson-Clement, Stefanos Alexandros Kontogouris, Marilyn Gatica, Mohammad Alkhawashki, Marcus Kaiser
Neuromodulation: Technology at the Neural Interface 2026 · 10.1016/j.neurom.2026.06.460
Abstract
Objectives Transcranial focused ultrasound stimulation (TUS) is an emerging neuromodulatory technique capable of modulating cortical and subcortical brain regions with high spatial precision. However, its effects on large-scale functional brain networks and their temporal evolution remain incompletely understood. This study investigated whether brief theta burst TUS induces target-specific alterations in functional brain network topology over the first hour after stimulation. Materials and methods A total of 22 healthy participants were randomly assigned to receive TUS targeting either the right inferior frontal cortex (IFC) or the right thalamus. Resting-state functional magnetic resonance imaging was acquired at baseline and at three minutes post stimulation intervals spaced 15 minutes apart. Graph-theoretical analyses quantified four centrality metrics (strength, expected influence, betweenness, and closeness) across 86 brain regions. Global network organization was assessed using small-worldness. Results IFC stimulation produced progressive reductions in regional network integration, initially affecting visual cortices and subsequently extending to right prefrontal and temporal regions, the insula, and the putamen, with peak effects occurring approximately 45 minutes post stimulation. IFC stimulation also increased global small-worldness, indicating a shift toward a more randomized network configuration. In contrast, thalamic stimulation resulted in a spatially circumscribed and temporally stable reduction in betweenness centrality within the left precuneus without widespread network alterations. Conclusions Brief theta burst TUS induces target-dependent and temporally evolving changes in large-scale functional brain organization. Cortical stimulation of the IFC produced distributed and progressive network reconfiguration, whereas thalamic stimulation yielded a focal and stable effect. These findings suggest that the magnitude and spatial extent of TUS-induced network modulation depend on the connectivity profile and topologic embedding of the stimulated structure.
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 / 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) | 535.7 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 10.22 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 54.51 | ✓✓✓⚑ |
A theta burst TUS protocol was used, consisting of a 500 kHz fundamental frequency, 20 ms pulse, 200 ms pulse repetition interval, 5 Hz pulse repetition frequency, 10% duty cycle, spatial-peak pulse-average intensity = 54.51 W/cm2, and a total duration of 80 seconds; participants received a single such session.
Exposure 2: Thal-TUS
Target: thalamus — “right thalamus”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS PRO TPO-203 / 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) | 552.4 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 9.95 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 54.51 | ✓✓✓ |
A theta burst TUS protocol was used, consisting of a 500 kHz fundamental frequency, 20 ms pulse, 200 ms pulse repetition interval, 5 Hz pulse repetition frequency, 10% duty cycle, spatial-peak pulse-average intensity = 54.51 W/cm2, and a total duration of 80 seconds; participants received a single such session.
Flags from extraction
randomised— Paper describes allocation as 'pseudo-randomly allocated' with group balancing by sex/age, not simple randomisation.exposures[0].in_situ.pressure_kpa— Table 1 reports simulated peak pressure/intensity separately at Target, Brain, Skull and Skin; the 'Target' row was used as the in-situ value for this exposure, but 'Brain' values (also in-situ) differ and are not captured by the single schema field.exposures[0].unspecified_domain.isppa_w_cm2— The protocol-level spatial-peak pulse-average intensity (54.51 W/cm2) is stated as a fixed driving parameter without specifying whether it is a free-field or in-situ value; placed in unspecified_domain.direction_of_effect— Effects are reported as graph-theoretic network metric changes (centrality, small-worldness), not as simple excitatory/inhibitory neural activity changes; classified as mixed_or_unclear.