Spatiotemporal Distributions of Acoustic Propagation in Skull During Ultrasound Neuromodulation
Wen Meng, Zhengrong Lin, Yanchang Lu, Xiaojing Long, Long Meng, Chang Su, Zhiqiong Wang, Lili Niu
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2024 · 10.1109/tuffc.2024.3383027
Abstract
There is widespread interest and concern about the evidence and hypothesis that the auditory system is involved in ultrasound neuromodulation. We have addressed this problem by performing acoustic shear wave simulations in mouse skull and behavioral experiments in deaf mice. The simulation results showed that shear waves propagating along the skull did not reach sufficient acoustic pressure in the auditory cortex to modulate neurons. Behavioral experiments were subsequently performed to awaken anesthetized mice with ultrasound targeting the motor cortex or ventral tegmental area (VTA). The experimental results showed that ultrasound stimulation (US) of the target areas significantly increased arousal scores even in deaf mice, whereas the loss of ultrasound gel abolished the effect. Immunofluorescence staining also showed that ultrasound can modulate neurons in the target area, whereas neurons in the auditory cortex required the involvement of the normal auditory system for activation. In summary, the shear waves propagating along the skull cannot reach the auditory cortex and induce neuronal activation. Ultrasound neuromodulation-induced arousal behavior needs direct action on functionally relevant stimulation targets in the absence of auditory system participation.
Abstract via europepmc.
Exposures
Exposure 1: Primary motor cortex (M1)
Target: primary motor cortex — “M1”
Device: custom-built · self-designed ultrasound transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,700 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500,000 | ✓✓✓⚑ |
| Duty cycle (%) | 50pulse duration × PRF gives 50000%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulation | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 592 | ✓✓✓⚑ |
Pulse repetition frequency 500 kHz (as written), pulse duration 1 ms, duty cycle 50%, sonication duration 1 s, interstimulus interval 2 s; stimulation delivered until righting reflex or for up to 30 min under 0.7%-0.8% isoflurane.
Consistency checks: pd exceeds period.
Exposure 2: Ventral tegmental area (VTA)
Target: ventral tegmental area — “VTA”
Device: custom-built · self-designed ultrasound transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,700 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500,000 | ✓✓✓⚑ |
| Duty cycle (%) | 50pulse duration × PRF gives 50000%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulation | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 592 | ✓✓✓⚑ |
Pulse repetition frequency 500 kHz (as written), pulse duration 1 ms, duty cycle 50%, sonication duration 1 s, interstimulus interval 2 s; stimulation delivered until righting reflex or for up to 30 min under 0.7%-0.8% isoflurane.
Consistency checks: pd exceeds period.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Paper states PRF as 500 kHz, which is inconsistent with a 1 ms pulse at 50% duty cycle (would be 500 Hz); recorded as written (500 kHz = 500000 Hz), probable typo.exposures[1].timing.pulse_repetition_frequency_hz— Same PRF 500 kHz typo as exposure 0; recorded as written.n_subjects— Total not stated. Five groups of n = 7 per target (VTA and M1 experiments); immunofluorescence used n = 6 per group; whether the same animals were used is not stated.sham_type— Sham mechanism not described. 'Uncoupled' group (no coupling gel between transducer and skull) acts as a blocked-transducer control.exposures[0].unspecified_domain.pressure_kpa— 'acoustic pressure was 592 kPa' with no domain stated.exposures[1].unspecified_domain.pressure_kpa— 'acoustic pressure was 592 kPa' with no domain stated.exposures[0].in_situ— Skull shear-wave simulation reported only intensity ratios (focus vs transducer surface, A1 vs focus), no absolute pressure or intensity.exposures[0].device— Transducer described as self-designed; no maker or model given beyond that.