40 Hz noninvasive transcranial ultrasound stimulation modulates multiscale nonlinear dynamics of hippocampal CA1 neural oscillations of Alzheimer’s mouse model

OBJECTIVE: Aberrant nonlinear dynamics of hippocampal neural oscillations are a hallmark of early network dysfunction in Alzheimer's disease (AD), with critical roles in memory processing. Although transcranial ultrasound stimulation (TUS) has shown cognitive benefits in AD models and patients, its effects on the nonlinear dynamics of hippocampal CA1 oscillations and their multiscale organization remain unclear. Approach. Here, we applied 40 Hz non-invasive TUS to the hippocampal CA1 region of AD mouse model and recorded local field potentials before, during, and after stimulation. Analyses integrated nonlinear dynamical metrics, power spectral dependencies, cross-frequency coupling, and event-level oscillatory features. Main results. We found that (1) 40 Hz TUS decreases complexity and irregularity of CA1 activity, and enhances dynamical activity and long-range temporal correlations in broadband and high-frequency ranges, increases complexity in the theta and beta bands. (2) TUS also significantly reduced theta-gamma and intra-gamma phase-amplitude coupling, while producing frequency-specific changes in the rate, amplitude, duration, and temporal organization of theta, gamma, and ripple events. (3) Furthermore, the relationship between nonlinear dynamics and power spectral density was modulated across stimulation phases. Significance. 40 Hz TUS can modulate multiscale nonlinear dynamics of neural oscillations in hippocampal CA1 of Alzheimer's mouse model, which lays a theoretical foundation for the clinical intervention of Alzheimer's disease via ultrasound stimulation. .