Low frequency ultrasound elicits broad cortical responses inhibited by ketamine in mice

Abstract

The neuromodulatory effects of >250 kHz ultrasound have been well-demonstrated, but the impact of lower-frequency ultrasound, which can transmit better through air and the skull, on the brain is unclear. This study investigates the biological impact of 40 kHz pulsed ultrasound on the brain using calcium imaging and electrophysiology in mice. Our findings reveal burst duration-dependent neural responses in somatosensory and auditory cortices, resembling responses to 12 kHz audible tone, in vivo. In vitro brain slice experiments show no neural responses to 300 kPa 40 kHz ultrasound, implying indirect network effects. Ketamine fully blocks neural responses to ultrasound in both cortices but only partially affects 12 kHz audible tone responses in the somatosensory cortex and has no impact on auditory cortex 12 kHz responses. This suggests that low-frequency ultrasound's cortical effects rely heavily on NMDA receptors and may involve mechanisms beyond indirect auditory cortex activation. This research uncovers potential low-frequency ultrasound effects and mechanisms in the brain, offering a path for future neuromodulation.

Abstract via europepmc.

Flags from extraction

• exposures[0].free_field.pressure_kpa — Table 1 gives peak-to-peak pressure 'in water' (235 kPa for 500 us bursts, 300 kPa otherwise); the paper states pressures are peak-to-peak unless noted.
• exposures[0].timing.pulse_repetition_frequency_hz — PRF is paired with TBD and duty cycle in Table 1 (200, 20, 0.4 Hz at 10%; 1000, 100, 2 Hz at 50%); CW has none.
• n_subjects — Animal and trial numbers appear only in figure panels and legends, no total is stated in the text.
• sham_type — A sham control was delivered in random order but its mechanism is not described; decoupling the transducer (no gel) and 12 kHz audible sound were separate comparison conditions (sound is not ultrasound and is not recorded as an exposure).
• exposures[1].unspecified_domain.pressure_kpa — 300 kPa is the in-water maximum of the 40 kHz transducer; the paper does not state where the pressure was specified for the slice setup.
• exposures[1].timing.duty_cycle_pct — Slice paradigms: in vivo parameters, then 50% DC with a 500 ms burst and CW; the 10% value is inferred from 'parameters employed in in vivo experiments' and is not separately stated for slices.
• exposures[2].timing.sonication_duration_s — Text says total exposure 500 ms; Fig. 4 legend mentions only a 1-s exposure for the 500 kHz condition.
• exposures[2].timing.pulse_duration_ms — Burst rule: '100 ms burst duration, 50% DC, 5 bursts' read as 100 ms pulses within a 500 ms total exposure.
• exposures[0].device.family — Maker named is Steiner & Martins (Langevin transducer); not in the closed list, so other_manufacturer.