Holographic transcranial ultrasound neuromodulation enhances stimulation efficacy by cooperatively recruiting distributed brain circuits
Hector Estrada, Yiming Chen, Théo Lemaire, Neda Davoudi, Ali Özbek, Qendresa Parduzi, Shy Shoham, Daniel Razansky
Nature Biomedical Engineering 2025, 10, 6-15 · 10.1038/s41551-025-01449-x
Abstract
Precision-targeted ultrasonic neuromodulation offers immense potential for studying brain function and treating neurological diseases. Yet, its application has been limited by challenges in achieving precise spatio-temporal control and monitoring of ultrasound effects on brain circuits. Here we show that transcranial ultrasound elicits direct and highly focal responses, which can be dynamically steered at spatio-temporal scales relevant for neural function. Furthermore, holographic transcranial ultrasound stimulation allows direct control of the stimulated volume and actively modulates local and mid-range network projections, effectively lowering the activation threshold by an order of magnitude. To better understand this previously unexplored excitability regime not fully explained by the conventional pressure-frequency dyad, we developed a dual modelling framework, where both an empirical and a mechanistic model were constructed to capture the intricacies of holographic transcranial ultrasound stimulation. These models achieve qualitative agreement with our experimental results, suggesting that these findings are predominantly driven by putative network interactions. Our results bring insight on the complex interaction mechanisms of ultrasound with neural tissue and highlight its potential for the noninvasive interfacing of distributed brain networks.
Abstract via europepmc.
Exposures
Exposure 1: TUS and holographic TUS (hTUS) stimulation of mouse somatosensory cortex
Target: primary somatosensory cortex — “primary somatosensory cortex— lower limb region”
Device: IGT / Imasonic · Imasonic SaS ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.15 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 900, 1,100, 1,200, 2,300, 2,500, 2,800swept | ✓?⚑ |
| In-situ Isppa (W/cm²) | 20, 131swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | not reported |
The right hemisphere was sonicated 20 times at 10 s intervals with continuous 150 ms US pulses (20<ISPPA<131 W/cm2). Beam steering delivered the same 150 ms pulses to different cortical loci with a 30 s total stimulation period (10 s between foci) repeated 10 times. hTUS delivered the same 150 ms, 3 MHz pulses simultaneously to 2-3 foci (170 elements/focus for a triangle, 102 elements/focus for a pentagon) arranged at 0.5-1 mm radius.
Flags from extraction
exposures[0]— Single-focus TUS and holographic TUS (hTUS) are combined into one exposure because both target the same site (mouse somatosensory cortex) at the same frequency (3 MHz), per the target x frequency rule, even though the two conditions use markedly different device configurations (single vs. simultaneous multi-focus beams) and pressure ranges (~2.3-2.8 MPa for TUS vs ~0.9-1.2 MPa for hTUS).exposures[0].in_situ.pressure_kpa— List combines activation-threshold pressures reported across the single-focus TUS (2.5, 2.8 MPa) and hTUS (0.9, 1.1, 1.2 MPa) experiments, described as 'delivered in mouse cortex'/'at the targeted location'; the paper does not use the words 'free field' or 'in situ' for these specific values, so the domain assignment is inferred from context.exposures[0].in_situ.isppa_w_cm2— ISPPA range (20-131 W/cm2) is given for the initial S1 dose-response experiment as the intensity of pulses sonicating the right hemisphere; domain (in-brain) inferred from context rather than stated explicitly.adverse_events— Paper states the parameters 'have previously been shown to cause no brain damage or other irreversible effects', citing a prior publication (ref. 29) rather than presenting a safety assessment from this study; recorded as not_reported rather than none_observed.n_sessions_per_subject— Each mouse underwent 20 repeated sonications at 10 s intervals within what appears to be a single continuous imaging session, but the paper never states a number of sessions per animal.