Trans-Spinal Focused Ultrasound Stimulation Suppresses Chemically-Induced Tremor in Mice

Abstract

Tremors are a frequently appearing symptom of various neurological disorders and are defined as involuntary, oscillatory movements of body parts. Current treatments for the management of tremors include deep brain stimulation and epidural electrical stimulation. Despite the proven effectiveness of both procedures, they are both invasive and thus present risks. In our recent work, we demonstrated that focused ultrasound is able to noninvasively modulate the motor pathway maintaining the sensory information intact. In this study, we further applied trans-spinal focused ultrasound for the management of tremors. Harmaline-induced (30mg/kg) essential tremor mouse model was used in this study. Once the tremor is apparent, the mouse was anesthetized with a ketamine-xylazine cocktail to allow the attachment of the ultrasound transducer over the T12 vertebra. The effect of sonication was evaluated based on muscle activity recorded by an electromyogram from the hind limb during a state of mild anesthesia, characterized by stable tremors and lack of voluntary movement. One min-period of pulsed sonication (tone-burst duration of 0.5 ms, pulse repetition frequency of 1 kHz) showed a temporary inhibition of tremors in the hind limb (Figure 1a). The trans-spinal application of ultrasound appeared to be a consistent, non-invasive method to suppress tremors (Figure 1b). Histology (H&E staining) showed an absence of hemorrhagic and neurodegenerative damage to the spinal cord. The outcome showed the ability of focused ultrasound to manage the tremor in safe and non-invasive manner. This study provides a stepping stone for the trans-spinal application of focused ultrasound to motor-related disorders.