Low intensity, continuous wave focused ultrasound reversibly depresses heart rate in anesthetized mice

Abstract

Focused ultrasound (FUS) can noninvasively and reversibly modulate brain activity. Observed motor activity or behavioral changes are commonly used to infer neuromodulatory effects. Changes in autonomic nervous system regulation such as heart and respiratory function can potentially be used for studying the effects of FUS neuromodulation that do not produce outwardly observable motor or behavioral activity. In this study, low pressure (850 kPa), long duration (120 s) continuous-wave (CW) FUS at 2 MHz was targeted such that the focus spanned the visual cortex, hippocampus, and thalamus. These parameters were shown to reversibly depress heart rate in in vivo mice anesthetized with sodium pentobarbital by an average of 8.1 ± 3.7%. Following stimulus offset, heart rate either increased or varied in trend. Higher pressure (2 MPa), short duration (0.3 s) pulses at the same frequency resulted in either small, transient increases in heart rate or no change. Thermocouple measurements show the peak temperature elevation in the dura to be approximately 2 °C. Thermal simulations predict a peak temperature increase in the brain of 2.3 °C. These results indicate that CW FUS can alter autonomic nervous system regulation through very low heating and show that cardiorespiratory responses can be altered as a result of FUS neuromodulation.