Noninvasive Ultrasonic Neuromodulation in Freely Moving Mice

Abstract

Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations.

Miniature ultrasound ring array transducers for transcranial ultrasound neuromodulation of freely-moving small animals

“…However, even for the larger animal, head-fixation was still required for the experiment. There exists only one study which reported neuromodulation of local field potential (LFP) using a miniature single-element transducer [16]. Since the same stimulation modality is preferred to translate the findings from pre-clinical to clinical trials, to observe…”

A Review of Electric Impedance Matching Techniques for Piezoelectric Sensors, Actuators and Transducers

“…Electric impedance can be matched with simple shunt and series inductors to cancel the reactive component of the transducer [107][108][109]. Optimization of the EIMNs with driver/receiver electronics for broadband application in high-frequency range is difficult.…”

Microelectromechanical Systems-Based Neurotools for Non-Invasive Ultrasound Brain Stimulation

“…Most of the previous works demonstrated ultrasound neuromodulation on immobile or sedated animals because commercially available transducers are often bulky, heavy, and requires a collimator [19][20][21][22][23][24][25]. Recently, three pioneering works on MEMS-based ultrasound transducers have successfully demonstrated in vivo neuromodulation in freely-moving behaving animals [38][39][40][41]. The first of these reports was based on a CMUT ring array composed of 32 elements with a 183-kHz resonant frequency [38,39].…”

“…The other two works were based on piezoelectric transducers (Table 1) [40,41]. Lee et al [41] developed a miniaturized tFUS system for freely-moving animals.…”

“…The developed freely-moving system was verified by performing tFUS in awake and anesthetized groups. Li et al [40] optimized the size of the PZT and produced piezoelectric transducers with 5 mm in diameter and 0.49 g in weight. By attaching a concave epoxy acoustic lens in front of the transducer, a lateral spatial resolution of 1.2 mm was achieved.…”