Characterization of Ultrasound‐Driven Localized Neural Activity In Vitro Using a Piezoelectric Micromachined Ultrasound Transducer: Investigating Neuromodulatory Mechanisms in the Auditory Cortex
Runo Kitahara, Takashi Tateno
IEEJ Transactions on Electrical and Electronic Engineering 2026 · 10.1002/tee.70263
Abstract
Ultrasound stimulation is a promising, low‐invasive technique that can activate deep brain regions with high spatial resolution; it holds potential for the treatment of various neurological disorders. However, the fundamental cellular mechanisms by which ultrasound induces neural activity remain incompletely understood. To address this issue, we developed a compact ultrasound stimulation device that was optimized for the local stimulation of individual neurons in vitro . We evaluated the ability of the device to induce neural activity through numerical simulations using a three‐dimensional model, and then validated these results through experimental measurements. We also analyzed calcium ion dynamics in the mouse auditory cortex in response to ultrasound stimulation; we identified four distinct patterns of calcium responses, including both excitatory and inhibitory activity. To explore the underlying mechanisms, we administered pharmacological agents that inhibit mechanosensitive ion channels. Collectively, our findings provide new insights into the biophysical mechanisms of ultrasound‐induced neural activation. © 2026 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.
Abstract via crossref.
Exposures
Exposure 1: Continuous-wave ultrasound stimulation of auditory cortex brain slice
Target: auditory cortex — “auditory cortex (acute coronal brain slice)”
Device: custom-built · piezoelectric micromachined ultrasound transducer (PMUT)
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 360 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓? |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 92.8 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 0.291 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
A single 200-ms continuous-wave ultrasound stimulation was delivered per trial, 3 s after the start of fluorescence recording (10 s total per trial); ten trials were conducted per slice with 30-s intertrial intervals. Responses were compared against sham (0 Pa) stimulation trials.
Flags from extraction
exposures[0].free_field.pressure_kpa— 92.8 kPa and 291 mW/cm2 were measured via hydrophone in water/calibration conditions at the stimulation voltage (60 Vpp); the paper does not separately report a pressure value measured with the brain slice in place, so domain is recorded as free-field rather than in-situ.n_subjects— n_subjects is recorded as the 16 brain slices analysed (from 8 mice); subject_unit is 'preparation' since ultrasound was delivered to slices, not directly to the source animals.