Ultrasound-Induced Synchronized Neural Activities at 40 Hz and 200 Hz Entrained Corresponded Oscillations and Improve Alzheimer's Disease Memory

Aims Neurological diseases like Alzheimer's disease (AD) with cognitive deficits show impaired theta, gamma, and ripple bands. Restoring these oscillations may be crucial for rescuing cognitive functions. Low-intensity transcranial ultrasound stimulation (TUS), a noninvasive neuromodulation method, offers high spatial resolution and deep penetration. However, it remains unclear how 40 Hz and 200 Hz TUS may improve memory in AD by regulating hippocampal oscillations. Methods We applied 40 Hz and 200 Hz TUS to the CA1 region of AD mice, performing memory assessments and CA1 electrophysiology recordings simultaneously. Results Our results showed that both 40 Hz and 200 Hz TUS significantly improved memory performance in AD mice by targeting the dorsal hippocampus and increasing power in corresponding frequency bands. Specifically, 40 Hz TUS enhanced gamma and ripple bands, while 200 Hz TUS strongly affected both. This enhancement increased during stimulation and persisted 5 days poststimulation. Improved coupling between theta and gamma oscillations indicated better hippocampal coordination with other brain regions. Additionally, 40 Hz TUS raised sharp wave ripple (SPW-Rs) incidence, and 200 Hz TUS increased both SPW-R incidence and duration, contributing to memory improvement. Behavioral performance significantly improved with TUS at both frequencies. Conclusion Ultrasound-induced synchronized neural activities at 40 Hz and 200 Hz entrained corresponding oscillations and improved memory in Alzheimer's disease.