Ultrasonic neuromodulation of the mouse cortex increases cardiorespiratory activity

Focused ultrasound (FUS) has demonstrated its ability to modulate neuronal activity in both cortical and subcortical brain regions in a noninvasive and safe fashion in mice, non-human primates, and humans. Rodent studies have shown that ultrasonic neuromodulation (UNMOD) can elicit motor responses in limbs and trigger pupil dilation. Little is known about the effect of ultrasonic neuromodulation of the CNS on the autonomic activity in mice, primarily due to the cardiorespiratory depression caused by the anesthesia used. However, urethane has limited effects on autonomic activity and brain hemodynamics. In this paper, we demonstrate that UNMOD of the cortex increases cardiorespiratory activity in mice. A 1.9-MHz single-element focused ultrasound transducer was used to apply pulsed ultrasound to the mouse cortex. Each animal was injected intraperitoneally with urethane (1500 mg/kg), allowing for a stable plane of anesthesia and experimental efficacy window often exceeding 4 hours with minimal effects on autonomic activity. Sonications were performed in a grid spanning the cortex centered at the Bregma skull suture and heart and breathing rates were acquired using a pulse oximeter. FUS resulted in significant increases in both breathing and heart rates immediately following sonication. This study demonstrated that FUS can have an autonomous excitatory effect invivo.