Phase-locked closed-loop ultrasound stimulation modulates theta and gamma rhythms in the mouse hippocampus

Previous studies have demonstrated that open-loop transcranial ultrasound stimulation (TUS) can modulate theta and gamma rhythms of the local field potentials (LFPs) in the mouse hippocampus; however, the manner in which closed-loop TUS with different pressures based on phase-locking of theta rhythms modulates theta and gamma rhythm remains unclear. In this study, we established a closed-loop TUS system, which can perform closed-loop TUS by predicting the peaks and troughs of the theta rhythm. Comparison of the power, sample entropy and complexity, and phase-amplitude coupling (PAC) between the theta and gamma rhythms under peak and trough stimulation of the theta rhythm revealed the following: (1) the variation in the absolute power of the gamma rhythm and the relative power of the theta rhythm under TUS at 0.6–0.8 MPa differ between peak and trough stimulation; (2) the relationship of the sample entropy of the theta and gamma rhythms with ultrasound pressure depends on peak and trough stimulation; and (3) peak and trough stimulation affect the PAC strength between the theta and gamma rhythm as a function of ultrasound pressure. These results demonstrate that the modulation of the theta and gamma rhythms by ultrasound pressure depends on peak and trough stimulation of the theta rhythm in the mouse hippocampus.