Transnasal ventral brainstem stimulation reverses anesthesia-induced unconsciousness in sheep

BACKGROUND: Brainstem reticular formation (BRF) is crucially involved in regulating arousal, making it a potential target for reversing general anesthesia. The transnasal approach provides a minimally invasive access to the ventral brainstem. However, whether this approach can effectively modulate arousal remains unknown. OBJECTIVE: To evaluate the efficacy of transnasal BRF electrical stimulation in reversing anesthesia-induced unconsciousness. METHODS: Three 12-month-old male sheep (40-50 kg) were implanted epidural/bone electrodes close to ventral brainstem via a transnasal approach. Under anesthesia-induced unconsciousness, electrical stimulation at varying intensities was then delivered through ventral brainstem (epidural and bone) and deep thalamic electrodes. Local field potentials were recorded from thalamic depth electrodes and frontoparietal subdural electrodes to quantify spectral power changes, with assessment of thalamocortical functional connectivity. RESULTS: Our findings showed that ventral brainstem stimulation altered cortical power in the unconscious state. Specifically, 5 mA 100Hz epidural stimulation of BRF from the ventral side stably induced partial reversal of cortical signals to awake-like features, triggered frontal lobe dynamic changes, reversed alpha-beta power anteriorization, and enhanced partial thalamocortical connectivity. CONCLUSIONS: A novel approach for modulation of consciousness networks and reversal of loss of consciousness, presenting a promising solution for the management of prolonged disorders of consciousness in the future.