Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits

Abstract

Electromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01 degrees C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion.

Abstract via europepmc.

Flags from extraction

• exposures[*].timing.sonication_duration_s — For most specific experiments the paper states pulse count and PRF but not an explicit single-train sonication duration; per instructions this was not computed and is left not_reported except where an overall study-wide range (26-333 ms) is given.
• exposures[0] — 0.25 MHz M1 exposure: individual per-waveform values for this specific frequency are only in Supplementary Table S1 (not present in the extracted main text); the numeric fields populated here are the study-wide ranges stated in the main text for all 20 waveforms (0.25-0.5 MHz) combined, not specific to 0.25 MHz alone.
• exposures[2] — 0.425 MHz M1 exposure: no frequency-specific numeric parameters are given in the main text (only in Supplementary Table S1, not available); only the frequency value itself is quotable.
• device.manufacturer — Two transducer part numbers are given (0.5 MHz Olympus NDT V301-SU; 0.3 MHz Ultran GS-300-D19) but it is not stated which transducer was used for the 0.25 MHz and 0.425 MHz conditions in the frequency-sweep experiment; manufacturer left not_reported for those two exposures.
• sham_type — Behavioural safety experiments reference 'sham-treated controls' (rotorod/wire-hang tasks) but the paper does not describe how the sham treatment was administered (e.g., inactive transducer vs. handling only); recorded as ['other'].
• n_sessions_per_subject — Most experiments used a single acute stimulation session, but a repeated-stimulation subset (n=5 mice) was tested on days 0, 7, and 14, and a behavioural safety cohort was tested pre-stimulation, 24 h, and 7 days post-stimulation; not reduced to one number given this heterogeneity across sub-experiments.
• exposures[1].in_situ.ispta_w_cm2 — This exposure aggregates three separate M1@0.35MHz experiments (LFP/MUA recording, unilateral EMG, c-fos mapping) sharing the same target and frequency, per the target x frequency exposure rule; ISPTA list contains the two distinct ISPTA values reported (36.20 and 42.90 mW/cm2, converted to 0.0362 and 0.0429 W/cm2).
• exposures[3].in_situ.ispta_w_cm2 — The list [0.06453, 0.1422, 0.3] W/cm2 aggregates three separate sentences (tail-twitch: 64.53 mW/cm2; BBB/synapse/behaviour safety: 142.20 mW/cm2; higher-intensity apoptosis check: 300 mW/cm2). Only one contiguous source quote can be keyed per field path, so the quote given here covers the 142.20 mW/cm2 value; the other two values are quoted verbatim within exposures[3].timing.protocol_description.