High pressure transcranial focused ultrasound stimulation induces parameter-dependent cell-type specific effects
Sandhya Ramachandran, Huan Gao, Keunhyung Lee, Pavlo Zolotavin, Katherine Bray, Chih-Yu Yeh, Siyi Wang, Lan Luan, Chong Xie, Kai Yu, Bin He
Microsystems & Nanoengineering 2026 · 10.1038/s41378-026-01391-1
Abstract
Transcranial focused ultrasound (tFUS) is a promising technique that has been shown to have high spatial precision, deep brain penetration, and cell-type specificity. Intracranial electrophysiological recordings can measure neural responses to tFUS with high spatial and temporal resolution, but conventional silicon-based multi-electrode arrays cause vibration artifacts induced by increased tFUS pressure. In this study, using an ultraflexible nanoelectric thread electrode, we demonstrate the cell-type selective effects of tFUS under high acoustic pressure with a broad range of ultrasound parameters. We observe that their flexibility mitigates vibrations, eliminating artifacts even at high pressure levels. We observed a positive nonlinear relationship between pressure levels and both time-locked and delayed spiking responses in multiple cell types. We show that higher pressure levels produce distinct response curves across independently varied ultrasound pulse repetition frequency and duty cycle, suggesting the need for further investigation of pressure effects.
Abstract via europepmc.
Exposures
Exposure 1: Rat S1, 1.5 MHz, pressure, duty-cycle and PRF sweeps
Target: primary somatosensory cortex — “primary somatosensory cortex (S1)”
Device: Sonic Concepts · Sonic Concepts, Inc. · customized H276 128-element random array (driven by Verasonics Vantage 128) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,500 | ✓✓✓ |
| Pulse duration (ms) | 0.004, 0.04, 0.0677, 0.1, 0.2, 0.3, 0.4, 1, 10swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 30, 300, 1,500, 3,000, 4,500swept | ✓✓✓ |
| Duty cycle (%) | 0.6, 6, 30, 60swept | ✓✓✓⚑ |
| Sonication duration (s) | 0.067 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | 100, 400, 700, 1,000, 1,300swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
505 trials per series with a 67 ms sonication every 2 s (10% trigger jitter). Pressure sweep at 1500 Hz PRF/30% DC and 30 Hz PRF/0.6% DC; duty cycle swept 0.6-60% at 1500 Hz PRF; PRF swept 30-4500 Hz at 30% DC, the last two each at 100 and 1300 kPa. Sham was ultrasound delivered off-target to the front of the skull.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— Pressures are described as predicted delivered peak-to-peak pressure and as estimated through the silicone-covered skull; domain not clearly free-field or in situ, so placed in unspecified_domain. Peak-to-peak, not peak negative. Intensities appear only in the supplementary table.exposures[0].timing.pulse_duration_ms— List assembled from tone-burst durations in several sentences (200 and 300 us in the pressure sweep, 4/40/200/400 us in the duty-cycle sweep, 10000/1000/200/100/67.7 us in the PRF sweep), converted to ms; the quote covers only the PRF-sweep durations.exposures[0].timing.sonication_duration_s— 67 ms total ultrasound duration per trial, one trial every 2 s with 10% jitter; converted to 0.067 s.n_subjects— Ten rats for electrophysiology (n = 10 per condition stated as a limitation); a separate cohort of four rats was used for temperature measurements and is not counted.exposures[0].timing.duty_cycle_pct— The pressure sweep used 30% DC at 1500 Hz and 0.6% DC at 30 Hz; those values are within the listed duty cycles.
Notes: Order of the five recordings within a series was random (same day); sham was off-target frontal skull stimulation.