Development of a miniaturized low-intensity ultrasound device to stimulate the central nervous system

Abstract

Low-intensity focused ultrasound (LIFU) has recently gained attention due to the potential to noninvasively and precisely stimulate the targeting area including deep body regions. In this work, we demonstrate a miniaturized LIFU device to stimulate the central nervous system, including the brain as well as the spinal cord. The results were assessed by cerebral hemodynamic, electrophysiological recording along with a behavioral examination. Materials & Methods Ultrasound stimulation was delivered by the custom-made transducer with a fundamental frequency of 450 kHz. The stimulation lasting a total of 300 ms consisted of 300 pulses, with 1 kHz pulse-repetition rate and 50% duty cycle. The motor cortex was selected during the brain stimulation, while L3 segment was a target for spinal cord modulation. Electroencephalogram and electromyography were recorded during spinal cord stimulation, and the brain sonication was assessed by an optical-based neural activity measurement, i.e. near-infrared spectroscopy. The behavioral responses were evaluated through video recording. Results In both scenarios, ultrasound stimulation was able to elicit the robust motor responses. The ultrasound-based spinal cord stimulation was able to induce the twitch of hind limbs with a delay of approximately 23 ms from the stimulation onset, while identical ultrasonic stimulation targeting muscle did not show any motor responses. In addition, the event-related potential was also observed in the somatosensory area triggered by the stimulation. The ultrasound brain stimulation produced the dominant ear movements. The optical neural recording has also shown the hemodynamic change linking with ultrasound-induced neural activity. The ear movements were replaced by gnawing behavior at specific animal by changing brain stimulation parameter. Conclusion The results verified the ability of low-intensity ultrasound to stimulate neurons at the central nervous system. The ultrasound stimulation may provide new hope for patients with Parkinson’s disease, epilepsy, dementia, chronic pain, and stroke symptoms.