The mouse motor cortex stimulation via non-invasive temporal interference transcranial focused ultrasound with microbubbles

Transcranial focused ultrasound (tFUS) has emerged as an innovative brain stimulation technology that uniquely integrates three characteristics: (a) non-invasive energy delivery, (b) submillimeter-scale spatial precision, and (c) effective penetration through cranial barriers to reach subcortical structures. Previous studies have shown that microbubbles (MBs) could amplify the mechanical effects of ultrasound, and the utilization of temporal interference ultrasound excitation effectively lowers cavitation thresholds. In this study, tFUS is applied to the motor cortex of both normal mice and MB-injected mice. Electromyography (EMG) recordings are utilized to analyze the effects of temporal interference (TI) ultrasound and single-frequency ultrasound stimulation on contralateral limb movements in mice. A hybrid model integrating the Gilmore-Akulichev-Zener (GAZ) model with nonlinear lipid membrane dynamics is developed, and numerical simulations of microbubble (MB) dynamics are performed to calculate the scattered pressure exerted by MBs on neurons. The study demonstrated that temporal interference ultrasound combined with MBs could increase the success rate of motor responses. The potential mechanism could be temporal interference ultrasound combined with MBs generate higher scattered pressures. The results demonstrated that temporal interference ultrasound combined with MBs could enhance neuronal activity in the Central Nervous System, enabling a highly specific method to increase the efficiency of tFUS stimulation.