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

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.