Ultrasound-driven piezoelectric current activates spinal cord neurocircuits and restores locomotion in rats with spinal cord injury

Background Neuromodulation via electrical stimulation (ES) is a common technique to treat numerous brain and spinal cord related neurological conditions. In the present study, we examined the efficacy of piezoelectric stimulation (pES) by a custom miniature piezostimulator to activate the spinal cord neurocircuit in comparison with conventional epidural ES in rats. Methods Stimulation electrodes were implanted on L2 and S1 spinal cord and were connected to a head-plug for ES, and a piezostimulator for pES. EMG electrodes were implanted into hindlimb muscles. To generate piezoelectric current, an ultrasound beam was delivered by an external ultrasound probe. Motor evoked potentials (MEPs) were recorded during the piezoelectric stimulation and compared with the signals generated by the ES. Results Our results suggest that ultrasound intensity as low as 0.1 mW/cm 2 could induce MEPs in the hindlimbs. No significant difference was found either in MEPs or in muscle recruitments for ES and pES. Similar to ES, pES induced by 22.5 mW/cm 2 ultrasound restored locomotion in paralyzed rats with complete thoracic cord injury. Locomotion EMG signals indicated that pES works same as ES. Conclusion We propose piezoelectric stimulation as a new avenue of neuromodulation with features overtaking conventional electrical stimulation to serve future bioelectronic medicine. 83StwwHHYaD7oZ4SVru6w9 Video abstract.