Closed-loop transcranial ultrasound stimulation based on NREM and REM sleep for bidirectional modulation of sleep neural oscillation and memory

Sleep plays an important role in memory integration. Closed-loop physical stimulation during rapid eye movement (REM) or non-rapid eye movement (NREM) sleep can modulate neural oscillations and associated memory functions. However, the impact of closed-loop transcranial ultrasound stimulation (CLTUS), a non-invasive technique with high spatial resolution and deep penetration, on sleep-specific oscillations and memory remains unclear. Approach: In this study, we developed a CLTUS system using deep learning to target NREM and REM sleep oscillations and evaluated sleep neural oscillations and memory ability. Main results: Our findings revealed that CLTUS of the slow oscillation up-state during NREM sleep reduced NREM-specific neural activity and significantly weakened spatial and fear memory abilities. These changes were positively correlated with the induced neural dynamics. Conversely, during REM sleep, CLTUS delivered at the theta peak enhanced REM-specific neural activity in both healthy and Alzheimer's disease model mice. Consequently, spatial memory was significantly improved in both groups, and this improvement was closely related to ultrasound-induced neural activity. Significance: CLTUS based on NREM and REM sleep exerts a bidirectional modulation effect on sleep neural oscillations and memory ability, providing important guidance for selecting and optimizing stimulation protocols for modulating sleep and memory.