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

Abstract

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.

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo

“…DBS, including electrical stimulation or epidural electrical stimulation, is a commonly used neurostimulation method. Epidural stimulation of the spinal cord plays a positive role in the functional recovery of the injured spinal cord [ 2 , 3 ]. However, because of the highly diffuse electric field and lower spatial resolution, it is difficult to locate a specific area of interest using electrical stimulation [ 4 ].…”

“…The spinal cord contains complex neurocircuits, the stimulation of which is an important method to treat chronic spine-related conditions, such as failed back surgery syndrome, complex regional pain syndrome, painful diabetic neuropathy, and spinal cord injury [ 3 , 24 – 28 ]. Recently, there has been growing interest in ultrasound neuromodulation; however, little is known about whether spinal cord stimulation with LIFU can activate or inhibit spinal cord neurocircuits and whether such stimulation causes injury to the spinal cord.…”

Low-Intensity Focused Ultrasound Alleviates Spasticity and Increases Expression of the Neuronal K-Cl Cotransporter in the L4–L5 Sections of Rats Following Spinal Cord Injury

“…In previous studies, we confirmed that LIFU can activate the neurocircuits of the spinal cord effectively (Liao et al, 2021a ). Li et al ( 2020 ) applied ultrasound-driven piezoelectric current to successfully activate the spinal cord neurocircuits of SCI rats. A clinical study confirmed that epidural electrical stimulation can modulate the spinal network of complete SCI patients and help recovery of the motor function of paraplegic patients (Gill et al, 2018 ; Ridler, 2018 ).…”

A novel therapeutic approach of ultrasound stimulation to restore forelimb functions following cervical cord injury in rats

“…The other ends of the wires were connect-ed to the pins of a head connector (SMC) to mount on the head of each rat. The piezoelectric element was then coated with a biocompatible material as described previously [24].…”