Low-intensity ultrasound activates vestibular otolith organs through acoustic radiation force

Abstract

The present study examined the efficacy of 5 MHz low-intensity focused ultrasound (LiFU) as a stimulus to remotely activate inner ear vestibular otolith organs. The otolith organs are the primary sensory apparati responsible for detecting orientation of the head relative to gravity and linear acceleration in three-dimensional space. These organs also respond to loud sounds and vibration of the temporal bone. The oyster toadfish, Opsanus tau, was used to facilitate unobstructed acoustic access to the otolith organs in vivo. Single-unit responses to amplitude-modulated LiFU were recorded in afferent neurons identified as innervating the utricle or the saccule. Neural responses were equivalent to direct mechanical stimulation, and arose from the nonlinear acoustic radiation force acting on the otolithic mass. The magnitude of the acoustic radiation force acting on the otolith was measured ex vivo. Results demonstrate that LiFU stimuli can be tuned to mimic directional forces occurring naturally during physiological movements of the head, loud air conducted sound, or bone conducted vibration.

Ultrasound Elicits Behavioral Responses through Mechanical Effects on Neurons and Ion Channels in a Simple Nervous System

“…We used a genetic approach to distinguish among these possibilities, leveraging mutants deficient in thermosensation or mechanosensation. To test for thermal effects, we compared ultrasound-evoked behaviors in wild-type and gcy-23(nj37)gcy-8(oy44)gcy-18(nj38) that lack a trio of receptor guanylate cyclases expressed exclusively in the AFD thermoreceptor neurons and are defective in thermotaxis (Garrity et al, 2010;Glauser and Goodman, 2016). Although these mutants have an intact AFD thermoreceptor neuron, they lack the ability to sense tiny (Ͻ0.05°C) thermal fluctuations in temperature (Ramot et al, 2008;Wasserman et al, 2011).…”

“…Low-intensity, focused ultrasound affects the function of excitable cells in the central (Fry et al, 1958;Meyers et al, 1959;Foster and Wiederhold, 1978;Gavrilov et al, 1996;Tufail et al, 2011;Yoo et al, 2011;Deffieux et al, 2013;King et al, 2013;Menz et al, 2013) and peripheral (Mihran et al, 1990;Tsui et al, 2005;Colucci et al, 2009) nervous systems, and the heart (Harvey, 1929;Buiochi et al, 2012). Because it propagates deep into tissue while retaining spatial focus, it has garnered considerable attention for its potential as a noninvasive tool for stimulation of the brain and the heart (Tufail et al, 2011;Lee et al, 2016).…”

Neuromodulation with transcranial focused ultrasound

“…The third and most probable form of mechanical energy is the acoustic radiation force (ARF). 24,52,54 The ARF is associated with momentum transfer from the ultrasound wave field to the medium; 10 the ARF exerts a steady pressure on a target throughout the time of ultrasound application. This steady pressure may stretch a cell membrane to an extent that affects conformation states of ion channels or other active molecules tied to the membrane.…”

Ultrasound elicits behavioral responses through mechanical effects on neurons and ion channels in a simple nervous system

“…5A). The third and most probable form of mechanical energy underlying the effects in this study is the acoustic radiation force (Trahey et al, 2004;Sarvazyan et al, 2010;Iversen et al, 2017). Acoustic radiation forces result from differences in acoustic intensities at individual points in space.…”

“…Consistent with this idea, ultrasound stimulation has been shown to increase currents carried by two-pore domain (K2P) potassium channels and voltage-gated sodium channels expressed in Xenopus oocytes (Kubanek et al, 2016). This body of work has raised the question whether or not ultrasound affects nervous systems via thermal or non-thermal effects (Iversen et al, 2017) and, if non-thermal effects are dominant, how is ultrasound transduced into membrane strain (tension) and channel activation. To contribute additional insight into these questions, we developed a behavioral-genetic assay using C. elegans roundworms.…”