High-Resolution Focused Ultrasound Neuromodulation Induces Limb-Specific Motor Responses in Mice in Vivo

Aurup, Christian; Kamimura, Hermes A. S.; Konofagou, Elisa E.

doi:10.1016/j.ultrasmedbio.2020.12.013

Cited by 22 publications

(18 citation statements)

References 32 publications

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“…Ultrasound applied was of 0.5 MHz frequency, 1kHz PRF, 50% duty cycle. Consistent with previous studies, contralateral limb movement and EMG signal could be induced by ultrasound stimulation (Ye, et al, 2016;Aurup et al, 2021) To directly measure neuronal activity, we used fiber photometry to record calcium signal changes in P1KO and Ctrl mice expressing GCaMP6s (Fig 2G , S4). Ultrasound at 0.5 MHz frequency, 1kHz PRF, 50% duty cycle, 300ms duration and acoustic pressures between 0.02 -0.12 MPa were used to stimulate the brains.…”

Section: Cortical Piezo1 Is An Important Mediator For Ultrasound-indu...supporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

“…In acute brain slices, ultrasound-induced calcium influx was significantly reduced in P1KO neurons and in neurons pre-treated with the broad mechanosensitive ion channel blocker ruthenium red (RR) (Drew, 2002) compared to those with functional Piezo1. We also used in vivo motor responses as a gauge of ultrasound stimulation as in previous studies (Aurup et al ., 2021; Ye et al ., 2016). P1KO mice displayed lowered responses to ultrasound stimuli in the motor cortex, measured by reduced contralateral limb movement, reduced muscle EMG responses, and reduced calcium signaling and c-Fos expression.…”

Section: Introductionmentioning

confidence: 99%

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The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Zhu

Xian

Hou

et al. 2023

Preprint

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Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of non-invasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1, was studied through a conditional knockout mouse model as a major molecule for ultrasound neuromodulation ex vivo and in vivo. We showed that Piezo1 knockout in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement and muscle EMG responses. We also detected higher Piezo1 in the central amygdala (CEA) which were found more sensitive to ultrasound stimulation than that of cortex. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation while knocking out astrocytic Piezo1 showed no obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory cortical activation and using smooth waveform ultrasound with randomized parameters to stimulate P1KO ipsilateral and contralateral regions of the same brain and recording evoked movement in the corresponding limb. Thus, we demonstrate that Piezo1 is functionally expressed in different brain regions, and that it is an important mediator of ultrasound neuromodulation in the brain, laying the ground for further mechanistic studies of ultrasound.

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Section: Cortical Piezo1 Is An Important Mediator For Ultrasound-indu...supporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Zhu

Xian

Hou

et al. 2023

Preprint

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“…The right image shows the organs included in the model. somatosensory brain circuits or elicit skin sensations in the subject [7,8,9], which may dependent on the FUS frequency [10,3]. A number of fundamental questions are raised by these observations, including the mechanisms responsible for direct and off-target effects, the frequency-dependence of such effects and their spatial distribution.…”

Section: Introductionmentioning

confidence: 99%

Mechanics Of Ultrasonic Neuromodulation In A Mouse Subject

Salahshoor

Guo

Shapiro

et al. 2021

Preprint

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Ultrasound neuromodulation (UNM), where a region in the brain is targeted by focused ultrasound (FUS), which, in turn, causes excitation or inhibition of neural activity, has recently received considerable attention as a promising tool for neuroscience. Despite its great potential, several aspects of UNM are still unknown. An important question pertains to the off-target sensory effects of UNM and their dependence on stimulation frequency. To understand these effects, we have developed a finite-element model of a mouse, including elasticity and viscoelasticity, and used it to interrogate the response of mouse models to focused ultrasound (FUS). We find that, while some degree of focusing and magnification of the signal is achieved within the brain, the induced pressure-wave pattern is complex and delocalized. In addition, we find that the brain is largely insulated, or 'cloaked', from shear waves by the cranium and that the shear waves are largely carried away from the skull by the vertebral column, which acts as a waveguide. We find that, as expected, this waveguide mechanism is strongly frequency dependent, which may contribute to the frequency dependence of UNM effects. Our calculations further suggest that off-target skin locations experience displacements and stresses at levels that, while greatly attenuated from the source, could nevertheless induce sensory responses in the subject.

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“…The intersection of engineering and health science enables the investigation of FUS's ability to interfere with brain activity in a safe, customized, and non-invasive manner. FUS can probe spatially specific brain regions non-invasively [4,12], and in the case of peripheral nerves, the pulsing regime dictates excitatory or inhibitory effects [13][14][15][16]. Pouget et al demonstrate that transcranial ultrasound stimulation using a repetitive pulse sequence can modulate the visuomotor behavior of nonhuman primates, demonstrating for the first time that repetitive transcranial ultrasound (rTUS) assisted by neuronavigation [17] can have a sustained effect on monkey behavior with a quantified return-time to baseline (18-31 min).…”

mentioning

confidence: 99%

Editorial: Magnetic Resonance-Guided Focused Ultrasound: Physical Principles and Biomedical Applications

et al. 2021

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High-Resolution Focused Ultrasound Neuromodulation Induces Limb-Specific Motor Responses in Mice in Vivo

Cited by 22 publications

References 32 publications

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Mechanics Of Ultrasonic Neuromodulation In A Mouse Subject

Editorial: Magnetic Resonance-Guided Focused Ultrasound: Physical Principles and Biomedical Applications

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