Low-intensity transcranial focused ultrasound (tFUS) is a non-invasive brain stimulation tool for safely and reversibly modulating brain circuits. The effectiveness of tFUS on human brain has been demonstrated, but how tFUS influences the human voluntary motor processing in the brain remains unclear. Based on individual brain model derived from 3T magnetic resonance imaging, we applied the tFUS (spatial peak pressure: 809.2 kPa, spatial-peak pulse-average intensity: 5.90 W/cm2) to modulate the movement-related cortical potential (MRCP) originating from human subjects (N=15) practicing a voluntary foot tapping task. The subjects were instructed to initiate pressing the foot pedal using their right leg roughly every 3-5 seconds on their own discretion. Concurrently, 64-channel electroencephalograph (EEG) was recorded and used to reconstruct the brain source activity specifically at the primary leg motor cortical area using the electrophysiological source imaging (ESI) with the minimum norm estimation. The ESI illustrated the ultrasound modulated MRCP source dynamics with high spatiotemporal resolutions. The MRCP source was reconstructed and evaluated for assessing the tFUS neuromodulatory effects on the voluntary MRCP. Moreover, the effect of ultrasound pulse repetition frequency (UPRF) was assessed in modulating the MRCP. The ESI results showed that tFUS significantly increased the MRCP source profile amplitude (MSPA) comparing to a sham ultrasound condition (PRF 300Hz vs. Sham US: p = 0.002; PRF 3000Hz vs. Sham US: p = 0.0001), and further, a high UPRF (i.e., 3000 Hz) enhanced the MSPA more than a low UPRF (i.e., 300 Hz) did (PRF 300Hz vs. PRF 3000Hz: p = 0.013). No adverse symptom was reported by our human subjects. This work provides the first evidence of tFUS enhancing the human endogenous motor cortical activities through excitatory modulation. Since motor imagination can also evoke the MRCP, the demonstrated neuromodulation by tFUS would lead to more applications in motor rehabilitation/prosthesis scenarios.
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