Temporal dynamics of offline transcranial ultrasound stimulation

Cyril Atkinson-Clement, David Howett, Mohammad Alkhawashki, James Ross, Ben Slater, Marilyn Gatica, Fabien Balezeau, Chencheng Zhang, Jerome Sallet, Chris Petkov, Marcus Kaiser

Current Research in Neurobiology 2025, 8, 100148 · 10.1016/j.crneur.2025.100148

nonhuman primatehealthyfmriother mri

Abstract

Transcranial ultrasound stimulation (TUS) is a promising non-invasive neuromodulation modality, characterized by deep-brain accuracy and the capability to induce longer-lasting effects. However, most TUS datasets are underpowered, hampering efforts to identify TUS longevity and temporal dynamics. This primate case was studied awake with over 50 fMRI datasets, with and without left anterior hippocampus TUS. We therefore amassed the highest-powered TUS dataset to date required to reveal TUS longevity and dynamics. Most of the effects were found in the TUS region itself and alongside the default mode and sensorimotor networks. Seed-based functional connectivity exhibited a time-constrained alteration which dissipated ∼60 min post-TUS. Intrinsic activity measure and regional homogeneity displayed extended diffusivity and longer durations. This high-powered dataset allowed predicting TUS using pre-stimulation features that can now extend to modeling of individuals scanned less extensively. This case report reveals the diversity of TUS temporal dynamics to help to advance long-lasting human applications.

Abstract via europepmc.

Speciesrhesus macaque (Macaca mulatta)

Subjects1 animals

Sessions per subject9

Randomisednot reported

Blindingnot reported

Sham / controlinactive transducer

Auditory controlnot reported

Readout timingoffline

Anaesthesiaawake

Readoutsfmri, other mri — Seed-based resting-state functional connectivity (R2) from left anterior hippocampus; fractional amplitude of low-frequency fluctuations (fALFF); regional homogeneity (ReHo); diffusion-weighted imaging tractography for structural connectivity

Direction of effectbidirectionalTUS of the left anterior hippocampus increased functional connectivity (R2) between the hippocampus and distant regions (cerebellum, V2, orbitofrontal cortex, premotor cortex) in a time-constrained window (~40-60 min post-TUS); fALFF and ReHo showed both increases (e.g. putamen, pons, inferior temporal cortex) and decreases (e.g. posterior medial cortex, parietal lobules, hippocampus) over a more extended and region-specific time course lasting up to at least 100 min.

Adverse eventsnot reported

Exposures

Exposure 1: Offline TUS of left anterior hippocampus

Target: hippocampus — “left anterior hippocampus”
Device: Sonic Concepts · Sonic Concepts Inc. · H115-MR ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	250	✓✓✓
Pulse duration (ms)	30	✓✓✓
Pulse repetition frequency (Hz)	10	✓✓✓
Duty cycle (%)	30pulse duration × PRF gives 30%	✓✓✓
Sonication duration (s)	40	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	682	✓✓✓
Free-field Isppa (W/cm²)	15.5	✓✓✓
Free-field Ispta (W/cm²)	4.26	✓✓✓
In-situ estimate	simulationsingle value
In-situ pressure (kPa)	548	✓✓✓
In-situ Isppa (W/cm²)	10	✓✓✓
In-situ Ispta (W/cm²)	2.76	✓✓✓

Protocol, in the paper’s words

A commonly used primate 'offline' TUS protocol (250 kHz, 30 ms bursts, 100 ms pulse-repetition interval, 30% duty cycle, 40 s total duration) was applied once per TUS session via a single-element transducer coupled through a water-filled cone, targeting the left anterior hippocampus under stereotaxic neuronavigation; rs-fMRI was acquired 32-91 min afterward (median scan time used for modelling).

Flags from extraction

direction_of_effect — Effects vary substantially by neural metric and region: functional connectivity (R2) showed increases only, while fALFF and ReHo showed both increases and decreases depending on brain region; coded as bidirectional at the whole-study level.