Transcranial Focused Ultrasound of the Human Subgenual Anterior Cingulate Reconfigures Resting State Connectivity: A Sham-Controlled fMRI Study
Amilcar Malave, Emily Valera, Andrew Birnbaum, Elisa Konofagou, Jacek P. Dmochowski
2025 · 10.64898/2025.12.10.693481
Abstract
Transcranial focused ultrasound stimulation (tFUS) can modulate human brain activity, but its impact on large-scale functional connectivity (FC) in vivo remains incompletely characterized. Here we asked whether brief tFUS to the subgenual anterior cingulate cortex (sgACC) modulates its FC with other brain regions. In a sham-controlled, within-subject study of healthy adults ( N = 16), we measured resting-state blood-oxygen-level dependent (BOLD) activity with functional magnetic resonance imaging (fMRI) before, during, and after five minutes of tFUS (i.e., five 20-second sonications followed by 40 second pauses). Subject-level sgACC–whole-brain FC was analyzed with a linear mixed-effects model (fixed: time, condition, time×condition; random: subject). tFUS increased sgACC-whole brain connectivity after sonication relative to sham. A smaller, non-significant trend was observed during sonication. Baseline-controlled analyses were employed to rule out the possibility that the observed increase in FC was due to a “regression to the mean” effect. Interestingly, network-level analysis revealed a clear disassociation in the evolution of resting-state FC across the 15 minute recordings: during sham sessions, the sgACC’s connectivity with the default mode network (DMN) increased, while FC with other networks was largely unchanged. On the other hand, active tFUS led to a notable increase in FC with non-DMN networks (especially the cognitive control network), while connectivity with the DMN was stable. These results provide whole-brain evidence that tFUS reconfigures network dynamics in the human brain, motivating clinical applications to disorders characterized by dysregulated brain activity.
Abstract via europepmc.
Exposures
Exposure 1: Active tFUS to right sgACC
Target: subgenual anterior cingulate cortex — “subgenual anterior cingulate cortex (sgACC)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500 transducer driven by NeuroFUS ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 7.5 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 40 | ✓✓✓ |
| Duty cycle (%) | 30 | ✓✓✓ |
| Sonication duration (s) | 20 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.667 | ✓✓✓⚑ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Five 20-s sonications with a 40-s interval between sonications, delivered at 300 s into a 15-min resting-state fMRI run; PRF 40 Hz, duty cycle 30%.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Pulse duration not stated; not computed.exposures[0].free_field.ispta_w_cm2— Paper states Ispta = 667 mW/cm2 measured in water under free-field conditions; converted to W/cm2.sham_type— Sham session: 'no sonication was applied'; mechanism (powered off, etc.) not described.blinding— Paper does not state whether participants or experimenters were blinded.