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Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound

Abstract

Brain stimulation methods are indispensable to the study of brain function. They have also proven effective for treating some neurological disorders. Historically used for medical imaging, ultrasound (US) has recently been shown to be capable of noninvasively stimulating brain activity. Here we provide a general protocol for the stimulation of intact mouse brain circuits using transcranial US, and, using a traditional mouse model of epilepsy, we describe how to use transcranial US to disrupt electrographic seizure activity. The advantages of US for brain stimulation are that it does not necessitate surgery or genetic alteration, but it confers spatial resolutions superior to other noninvasive methods such as transcranial magnetic stimulation. With a basic working knowledge of electrophysiology, and after an initial setup, ultrasonic neuromodulation (UNMOD) can be implemented in less than 1 h. Using the general protocol that we describe, UNMOD can be readily adapted to support a broad range of studies on brain circuit function and dysfunction.

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Figure 1: Basic ultrasonic brain stimulation rig and UNMOD waveform generation.
Figure 2: Preparation of electromyographic recordings to monitor US-evoked stimulation of intact motor cortex.
Figure 3: Electrophysiological recordings in response to brain stimulation with transcranial pulsed ultrasound.
Figure 4: Induction and disruption of electrographic seizure activity using UNMOD.

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Acknowledgements

Support for this work was provided by start-up funds from Arizona State University to W.J.T. and Department of Defense grants from the US Army Research, Development, and Engineering Command (RDECOM W911NF-09-0431) and a Defense Advanced Research Projects Agency Young Faculty Award (DARPA N66001-10-1-4032) to W.J.T.

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Authors

Contributions

Y.T., A.Y., S.P. and W.J.T. designed and conducted the experimental procedures. Y.T., A.Y., M.M.L. and W.J.T. analyzed and interpreted data from the experiments. Y.T., A.Y., S.P., M.M.L. and W.J.T. wrote the manuscript.

Corresponding author

Correspondence to William J Tyler.

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Competing interests

W.J.T. is a cofounder of SynSonix.

Supplementary information

Supplementary Video 1

Overview of ultrasonic neuromodulation rig and equipment (MOV 30900 kb)

Supplementary Video 2

Disruption of seizure activity with TPU (MOV 8962 kb)

Supplementary Video 3

Disruption of electrographic seizure activity with continuous wave UNMOD waveforms (MOV 1490 kb)

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Tufail, Y., Yoshihiro, A., Pati, S. et al. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat Protoc 6, 1453–1470 (2011). https://doi.org/10.1038/nprot.2011.371

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