Abstract
Ultrasonic (US) neuromodulation has emerged as a promising therapeutic means by delivering focused energy deep into the tissue. Low-intensity ultrasound (US) directly activates and/or inhibits neurons in the central nervous system (CNS). US neuromodulation of the peripheral nervous system (PNS) is less developed and rarely used clinically. Literature on the neuromodulatory effects of US on the PNS is controversy with some documenting enhanced neural activities, some showing suppressed activities, and others reporting mixed effects. US, with different range of intensity and strength, is likely to generate distinct physical effects in the stimulated neuronal tissues, which underlies different experimental outcomes in the literature. In this review, we summarize all the major reports that documented the effects of US on peripheral nerve endings, axons, and/or somata in the dorsal root ganglion. In particular, we thoroughly discuss the potential impacts by the following key parameters to the study outcomes of PNS neuromodulation by the US: frequency, pulse repetition frequency, duty cycle, intensity, metrics for peripheral neural activities, and type of biological preparations used in the studies. Potential mechanisms of peripheral US neuromodulation are summarized to provide a plausible interpretation to the seemly contradictory effects of enhanced and suppressed neural activities from US neuromodulation.
Highlights
Our nervous system consists of the central and peripheral nervous systems (CNS, PNS), which have similar ion channel/modulator compositions [1,2]
In the central nervous system (CNS), functional neural circuits implicated in different neurological diseases overlap significantly with one another, and certain neural circuits are not restricted to one region but spread throughout the brain
Along with some other research groups, have demonstrated that US stimulation on the PNS, with ISPTA between 1 and 200 W/cm2, is unlikely to induce a sufficient temperature change in the target region to elicit temperature-driven neuromodulation [43,47]. This intermediate intensity range has been explored on the PNS by several neuromodulation studies, which have been systematically reviewed in the subsequent sections
Summary
Our nervous system consists of the central and peripheral nervous systems (CNS, PNS), which have similar ion channel/modulator compositions [1,2]. TUS of the supplementary motor area and frontal polar cortex causes those brain regions to interact more selectively with the rest of the brain Outcomes of those researches have led to the successful translation of US stimulation, after approval by the U.S Food and Drug Administration (FDA), to treat medical-refractory patients with essential tremor [26]. Two most recent studies suggest that US neuromodulation of the CNS does not directly activate brain regions in mice, but through an indirect auditory cochlear pathway [29,30] These recent results from whole-organ and whole-animal studies do not invalidate the prior studies in reduced systems, which show apparent neuromodulation by focused US in the absence of a functioning auditory system, like in Caenorhabditis elegans, tissue culture, retina [31], and brain slices (reviewed in reference [9]).
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