Spinal Cord Ultrasound Stimulation Modulates Corticospinal Excitability
Background: Low-intensity focused ultrasound (LIFU) offers superior tissue penetration and enables precise neuromodulation of cortical and subcortical circuits. However, its effects on neural activity in the human spinal cord remain largely unexplored. Objective: To investigate the effects of LIFU on spinal cord neuromodulation under varying conditions of intensity (spatial-peak pulse-average intensity, ISPPA), duty cycle (DC), and pulse repetition frequency (PRF). Methods: Thirty-six healthy human volunteers participated in the study. A 500 kHz ultrasound transducer with a focal depth exceeding 100 mm was used to target the C8 spinal cord. Transcranial magnetic stimulation (TMS) was applied to the primary motor cortex (M1) hotspot corresponding to the first dorsal interosseous (FDI) muscle, innervated by the C8 nerve. A 500 ms-duration LIFU was delivered to the C8 spinal cord 400 ms prior to single-pulse TMS over the FDI hotspot. Spinal cord ultrasound stimulation (SCUS) was administered with varying acoustic parameters: intensities (ISPPA: 2.5 and 10 W/cm2), DCs (10% and 30%), and PRFs (500 and 1000 Hz). Changes in corticospinal excitability were assessed by comparing TMS-elicited motor-evoked potentials (MEPs) between active and sham SCUS conditions. Results: SCUS with an ISPPA of 10 W/cm2, a DC of 30%, and a PRF of 1000 Hz significantly reduced MEP amplitudes compared to sham stimulation. However, at the high intensity (ISPPA of 10 W/cm2), varying the DC between 10% and 30% did not affect MEP amplitudes. Additionally, while a PRF of 1000 Hz decreased MEP amplitudes at 10 W/cm2, a PRF of 500 Hz did not produce significant changes. Conclusions: The results indicate that ultrasound stimulation of the spinal cord can suppress corticospinal drive to muscles, especially when utilizing high intensity and high PRF parameters. This suggests that ultrasound stimulation may provide a novel method for modulating human spinal neural activity.