Low-intensity transcranial ultrasound stimulation improves motor behavior and modulates cortical functional network connectivity in mice with ischemic stroke.

The recovery of motor function in patients with ischemic stroke is closely related to the plastic remodeling of cortical functional networks. Low-intensity transcranial ultrasound stimulation (TUS) has been shown to improve motor behavior in patients with ischemic stroke and modulate cortical functional networks in healthy individuals. However, whether motor improvement after TUS is associated with cortical functional network reorganization remains unclear. Therefore, in this study, we constructed a mouse model of ischemic stroke using male C57BL/6 mice and simultaneously recorded the local field potential and gait behavior data of the whole-brain cortex of mice in a free-walking state before and after ultrasound intervention. Gait parameters, cortical functional network connectivity, and topology were systematically analyzed, and the correlations between behavioral indicators and network connectivity were explored. Our findings revealed that TUS significantly improved motor function in the mouse model, modulated cortical functional network connectivity to restore it to a healthy state, enhanced global information integration ability, optimized local separation efficiency, and restored gait phase transition control. Furthermore, the TUS-induced changes in the cortical functional network were positively correlated with behavioral improvement. This study confirmed that motor improvement after low-intensity TUS is accompanied by cortical functional network reorganization, and that such reorganization may contribute to post-stroke functional recovery.Significance Statement Stroke disrupts the neural networks essential for maintaining gait coordination. Although low-intensity TUS stimulation can improve post-stroke motor performance, how it remodels and restores cortical functional network connectivity during natural behavior remains unclear. This study combined free-walking gait with simultaneous acquisition of cortical local field potentials to conduct a 7-day targeted ultrasound modulation intervention in the infarct area in ischemic stroke mice. Results showed that TUS significantly improved gait and induced gait-phase-specific cortical functional network connectivity reconnection. This study provides evidence for the neural mechanisms by which ultrasound promotes post-stroke motor function recovery and offers a theoretical basis for the translational application of TUS in stroke treatment.