Noninvasive Ultrasound Stimulation of Ventral Tegmental Area Induces Reanimation from General Anaesthesia in Mice

Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness (DOC). However, these treatments require invasive procedures. This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice. Through the delivery of ultrasound energy to the ventral tegmental area, mice were aroused from an unconscious, anaesthetized state in this study, and this process was controlled by adjusting the ultrasound parameters. The mice in the sham group under isoflurane-induced, continuous, steady-state general anaesthesia did not regain their righting reflex. On insonation, the emergence time from inhaled isoflurane anaesthesia decreased (sham: 13.63 ± 0.53 min, ultrasound: 1.5 ± 0.19 min, p < 0.001). Further, the induction time (sham: 12.0 ± 0.6 min, ultrasound: 17.88 ± 0.64 min, p < 0.001) and the concentration for 50% of the maximal effect (EC50) of isoflurane (sham: 0.6%, ultrasound: 0.7%) increased. In addition, ultrasound stimulation reduced the recovery time in mice with traumatic brain injury (sham: 30.38 ± 1.9 min, ultrasound: 7.38 ± 1.02 min, p < 0.01). This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.