Mechanistic insights into ultrasonic neurostimulation of disconnected neurons using single short pulses

Weinreb, Eyal; Moses, Elisha

doi:10.1016/j.brs.2022.05.004

Cited by 19 publications

(22 citation statements)

References 87 publications

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“…The precise biomolecular and neurophysiological mechanisms of ultrasonic neuromodulation remain under rapidly progressing investigation (Weinreb & Moses, 2022; Yoo et al, 2022). Some theories focus on mechanical perturbation of neuronal lipid bilayer (El Hady & Machta, 2015; Heimburg & Jackson, 2005; Lemaire et al, 2019; Plaksin et al, 2014; Prieto et al, 2013), while others emphasize the role of mechanosensitive ion channels (Kubanek et al, 2018; Tyler et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Kop

Oghli

Grippe

et al. 2023

Preprint

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Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, and now stimulation protocols that optimize neuromodulatory efficacy for human application are required. One promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition. At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from pulsing TUS at audible frequencies. Across four experiments, one preregistered, at three independent institutions, we employed tightly matched control conditions to disentangle direct neuromodulatory effects of TUS from those driven by the salient auditory confound in a combined transcranial ultrasonic and magnetic stimulation paradigm. We replicated motor cortical inhibition following TUS, but showed through both controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation rather than direct neuromodulation. This study highlights the substantial impact of the auditory confound, invites a reevaluation of prior findings, and calls for appropriate control conditions in future TUS work. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for neuroscientific research and clinical applications.

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Section: Discussionmentioning

confidence: 99%

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Kop

Oghli

Grippe

et al. 2023

Preprint

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“…86,88 These parameters in different constellations can lead to variable transitions of underlying mechanisms determining the TUS effects. Currently, there are three dominant mechanisms considered to underlie neuromodulatory effects: cavitation, temperature and mechanical deformation 82,83 . While they can operate conjointly, the way they translate into molecular signals to neurons is unclear (Figure 2).…”

Section: The Underlying Mechanisms Of Ultrasonic Neuromodulationmentioning

confidence: 99%

“…For more information, see https://creativecommons.org/licenses/by-nc-nd/4.0/ activated due to further ultrasound-channel resonance and further exhibitory and inhibitory effects on voltage-dependent channels as shown in rats. 104,129 Interestingly, Weinreb et al (2022) showed within neuronal cultures that sonication via extremely short pulses induced action potentials in disconnected neurons eliminating networkeffects and enabling the examination on single-neuron level. 82 The study setup used for UFF 500 kHz, peak pressures of 0.35-1.32 MPa, and durations of 4 μs-40 ms extremely short ultrasound pulses and examined one by one the above introduced mechanisms.…”

Section: The Underlying Mechanisms Of Ultrasonic Neuromodulationmentioning

confidence: 99%

“…75,[77][78][79] In contrast to conventional NIBS the penetrability and focality of TUS is less limited by the biophysical instances when penetrating deep brain regions. [80][81][82][83] Thus, TUS appears to be a superior technique in terms of deep brain stimulation with its excellent focality, penetrability and steering capacities. 75,78,84 Furthermore, increasing studies in smaller animals [85][86][87] , monkeys [88][89][90] , sheep 91 and first-in-humans studies 92 are highlighting the potential safety and feasibility of TUS as a novel NIBS method.…”

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confidence: 99%

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Low-Intensity Focused Ultrasound Neuromodulation for Stroke Recovery: A Novel Deep Brain Stimulation Approach for Neurorehabilitation?

Yüksel

Sun

Latchoumane

et al. 2023

IEEE Open J. Eng. Med. Biol.

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Stroke as the leading cause of adult long-term disability and has a significant impact on patients, society and socio-economics. Non-invasive brain stimulation (NIBS) approaches such as transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tES) are considered as potential therapeutic options to enhance functional reorganization and augment the effects of neurorehabilitation. However, non-invasive electrical and magnetic stimulation paradigms are limited by their depth focality trade-off function that does not allow to target deep key brain structures critically important for recovery processes. Transcranial ultrasound stimulation (TUS) is an emerging approach for non-invasive deep brain neuromodulation. Using non-ionizing, ultrasonic waves with millimeter-accuracy spatial resolution, excellent steering capacity and long penetration depth, TUS has the potential to serve as a novel non-invasive deep brain stimulation method to establish unprecedented neuromodulation and novel neurorehabilitation protocols. The purpose of the present review is to provide an overview on the current knowledge about the neuromodulatory effects of TUS while discussing the potential of TUS in the field of stroke recovery, with respect to existing NIBS methods. We will address and discuss critically crucial open questions and remaining challenges that need to be addressed before establishing TUS as a new clinical neurorehabilitation approach for motor stroke recovery.

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“…To achieve the desired therapeutic effect, an activation of mechanosensitive ion channels induced by acoustic waves is the key part that ultrasound propagation travels through the non-brain tissues and cortical layers (Kamimura et al, 2020 ). Besides, the neuronal bilayer sonophore (NBLS) model has been developed for explaining the acoustic effect on the cell membrane and synapses of specific neurons at microscopic scale (Plaksin et al, 2016 ; Weinreb and Moses, 2022 ). It should be noted that cortical thickness represents an average of the distance from the inner surface of gyrus to the closest point on the outer surface of gyrus, containing six layers of neurons featured with cytoarchitectonic subdivisions (Amunts et al, 2013 ).…”

Section: The Importance Of Radiomic Features In Tusmentioning

confidence: 99%

Radiomics-Informed Modeling for Transcranial Ultrasound Stimulation: Age Matters

2022

Front. Neurosci.

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Mechanistic insights into ultrasonic neurostimulation of disconnected neurons using single short pulses

Cited by 19 publications

References 87 publications

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Low-Intensity Focused Ultrasound Neuromodulation for Stroke Recovery: A Novel Deep Brain Stimulation Approach for Neurorehabilitation?

Radiomics-Informed Modeling for Transcranial Ultrasound Stimulation: Age Matters

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