Low-intensity transcranial ultrasound stimulation suppresses abnormal neural oscillations in the motor cortex by stimulating STN in α-synucleinA53T mice

Previous studies have shown that low-intensity transcranial ultrasound stimulation (TUS) of the subthalamic nucleus (STN) in mice with Parkinson’s disease (PD) effectively suppresses pathological discharge activities in motor cortex. However, how TUS modulates the neural activity of the STN-motor cortex circuits, and the long-term effects of suppressing abnormal neural oscillations in α-synuclein A53T (α-syn) mice remain unclear. Here, we conducted STN-targeted ultrasound in α-syn mice, and examined the treatment efficacy via behavior test and electrophysiology in vivo. Alterations in neural activity patterns were specifically assessed in α-syn mice during pre- and post-therapeutic interventions. We found that TUS targeted at STN significantly (1) ameliorated abnormal neural activity in the STN, (2) reduced the neural correlation between STN and motor cortex, and (3) improved locomotor capability in α-syn mice. Thus, our results demonstrated that STN-targeted TUS rebalanced the neural activity in STN-motor cortex circuit, which was causally linked to the improvement of motor function in α-syn transgenic mice.