Tapered-window ultrasound stimulation directly evokes characteristic laminar responses in the mouse auditory cortex while minimizing peripheral auditory responses
Runo Kitahara, Masaki Sakagami, Ryo Furukawa, Takashi Tateno
Hearing Research 2026 · 10.1016/j.heares.2026.109740
Abstract
Transcranial ultrasound stimulation (TUS) is a minimally invasive technique used to modulate neuronal activity and target deep brain regions in small animal models and humans. However, TUS in small animals induces cortical responses that may be indirectly mediated via the peripheral auditory pathway rather than through direct cortical activation. Thus, this study presents a TUS method using tapered temporal envelopes to directly stimulate the auditory cortex (AC) and minimize peripheral auditory activation in small animals. We aimed to provide the minimal temporal parameters of continuous ultrasound stimuli that reduce auditory artifacts while reliably evoking localized responses in the mouse AC. We simultaneously recorded auditory brainstem responses (ABRs) and AC neural activity in normal hearing and ototoxically deafened mice. We evaluated the effects of varying the temporal envelope of continuous TUS on ABRs and cortical laminar responses. Rectangular waveforms with abrupt onset and offset edges elicited strong peripheral auditory responses in normal mice. By contrast, gradual tapering of the envelope suppressed ABRs while preserving AC activation. Notably, in ototoxically deafened mice, tapered envelope stimuli continued to evoke direct responses in the AC, indicating minimal peripheral involvement. These results demonstrate that appropriately shaping the temporal pattern of TUS enables direct stimulation of the AC with reduced peripheral activation. This approach highlights the potential of ultrasound-based neuromodulation to deliver stimulation signals directly to the cortex and influence plasticity within auditory neural circuits.
Abstract via europepmc.
Exposures
Exposure 1: Continuous-wave 500 kHz bursts with 0, 20 or 50 % tapered window, left auditory cortex
Target: auditory cortex — “left auditory cortex (AC)”
Device: Olympus / Panametrics · Olympus, USA · V301-SU planar transducer with custom-made waveguide ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0005, 0.001, 0.005, 0.01, 0.02swept | ✓✓✓ |
| Free-field pressure (kPa) | 67 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.152 | ✓✓✓⚑ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single continuous-wave bursts of 0.5, 1, 5, 10 or 20 ms with sinusoidal onset/offset windows totalling 0, 20 or 50 % of the duration (15 combinations). Repetitive pulsed stimulation was deliberately not used. Intertrial interval not stated for ultrasound; 512 repetitions per condition for MUA.
Flags from extraction
exposures[0].free_field.pressure_kpa— 67 kPa is at the waveguide surface; 32.2 kPa was measured 8 mm from the waveguide surface (where brain lies); four pressures 32.2-218 kPa were piloted. Hydrophone in water tank.exposures[0].free_field.ispta_w_cm2— 152 mW/cm2 converted to 0.152 W/cm2; tied to 67 kPa at waveguide surface.exposures[0].timing.waveform— Continuous wave with amplitude-tapered onset/offset (window); classed continuous as each stimulus is one uninterrupted burst, but envelope shaping is the independent variable.n_subjects— 16 normal-hearing mice; 4 further mice were ototoxically deafened and it is unclear whether these are part of the 16. Analysed n varies (5, 4, 3).exposures[0].in_situ— Skull attenuation stated to be negligible and ignored; no in situ values.sham_type— Sham was 0 V input to the transducer (0 kPa-driven stimulation).