A Miniature Ultrasound Source for Neural Modulation

This work describes a unique ultrasound (US) exposure system designed to create very localized ( $\sim 100 ~\mu \text{m}$ ) sound fields at operating frequencies that are currently being used for preclinical US neuromodulation. This system can expose small clusters of neuronal tissue, such as cell cultures or intact brain structures in target animal models, opening up opportunities to examine possible mechanisms of action. We modified a dental descaler and drove it at a resonance frequency of 96 kHz, well above its nominal operating point of 28 kHz. A ceramic microtip from an ultrasonic wire bonder was attached to the end of the applicator, creating a 100- $\mu \text{m}$ point source. The device was calibrated with a polyvinylidene difluoride (PVDF) membrane hydrophone, in a novel, air-backed, configuration. The experimental results were confirmed by simulation using a monopole model. The results show a consistent decaying sound field from the tip, well-suited to neural stimulation. The system was tested on an existing neurological model, Drosophila melanogaster, which has not previously been used for US neuromodulation experiments. The results show brain-directed US stimulation induces or suppresses motor actions, demonstrated through synchronized tracking of fly limb movements. These results provide the basis for ongoing and future studies of US interaction with neuronal tissue, both at the level of single neurons and intact organisms.

I. Introduction

Sound waves were first used to modulate neuronal activity in 1958 [1]. Since then, ultrasound (US) neuromodulatory effects have been demonstrated numerous times in multiple animal models [2], [3], [4], [5], [6], [7], [8], [9], including invoking auditory nerve responses [10], modifying nerve conduction [11], and inducing reproducible excitation of neuronal circuits in the motor cortex in excised rodent brains [12] and in live animals [13]. Currently, the technique is being explored in clinical studies of epilepsy, mood alteration, and disorders of consciousness [4], [14], [15], [16], [17]. US as a neuromodulation therapy has several unique advantages because it is: noninvasive; capable of reaching both shallow and deep brain locations; capable of focusing on a relatively small region of tissue; safe as currently used; and cost-effective. It, thus, provides a unique method of neuromodulation to complement others currently in use, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS).