Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation

Kai Yu, Xiaodan Niu, Esther Krook-Magnuson, Bin He

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.

Original languageEnglish (US)
Article number2519
JournalNature communications
Issue number1
StatePublished - Dec 1 2021

Bibliographical note

Funding Information:
This work was supported in part by NIH grants MH114233, EB029354, AT009263, EB021027, NS096761, and NSF grants CBET-1450956 and CBET-1264782. K.Y. was supported in part by The Samuel and Emma Winters Foundation, an MnDRIVE Neuromo-dulation Fellowship and Doctoral Dissertation Fellowship from the University of Minnesota. X.N. was supported in part by Liang Ji Dian Graduate Fellowship and Carnegie Mellon Neuroscience Institute Presidential Fellowship at Carnegie Mellon University. We thank Dr. Akira Sumiyoshi from Tohoku University for providing Wistar rat MRI atlas and Dr. Yijen Wu from Rangos Research Center Animal Imaging Core for providing micro-CT and MRI atlas of mice. We are also grateful to Drs. Abbas Sohrabpour and Haiteng Jiang for stimulating discussions, Dr. Qi Shao for coordinating histology studies, Dr. Yi Zhang for training in animal surgery, John Basile for assisting equipment setup, as well as Daniel Suma, Maryam Zhian, and Mckinney Zhang for assistance.

Publisher Copyright:
© 2021, The Author(s).


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