Objective. Focused ultrasound (FUS) has recently been demonstrated capable of exciting motor neuronal activity. However, comprehensive understanding of elucidated excitatory and inhibitory effects is required to better assess FUS-mediated modulation. In this study, we demonstrate that image-guided FUS can selectively modulate motor neuron activity in the mouse sciatic nerve in vivo and attribute motor responses to thermal effects. Approach. FUS was applied on the sciatic nerve of anesthetized mice in vivo through the intact skin and muscle using ultrasound imaging for targeting. Both excitatory and inhibitory effects were recorded using electromyography (EMG) along with muscle response of the hind limb. The effects of FUS modulation versus heating by invasive alternative heating source (AHS) on electrically evoked EMG responses in the sciatic nerve in vivo were also investigated. The safety and reversibility of the technique were validated using histology and EMG recovery. Main results. The FUS was capable of eliciting motor neuronal activity comparable to electrical stimulation ES, and facilitating motor neuronal response on electrically evoked potentials with temperature elevation up to 11.5 °C  ±  0.3 °C (PRF  ⩽  40 Hz). On the other hand, FUS-induced temperature elevations above 15.1 °C  ±  1.6 °C (PRF  ⩾  100 Hz) resulted in the suppression of electrically-evoked motor neuronal activity along with a decrease in EMG latency and area under the curve (AUC), which was validated against the invasive AHS with temperature elevation of 18.1 °C  ±  8.5 °C. Histological findings along with EMG responses after FUS modulation demonstrated a reversible or irreversible modulation. Significance. The findings reported herein indicate that image-guided FUS (PRF  ⩽  100 Hz) induces safe and controllable modulation of involuntarily evoked motor neuron activity in vivo.

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