Ultrasound has received widespread attention as an emerging technology for targeted, non-invasive neuromodulation based on its ability to evoke electrophysiological and motor responses in animals. However, little is known about the spatiotemporal pattern of ultrasound-induced brain activity that could drive these responses. Here, we address this question by combining focused ultrasound with wide-field optical imaging of calcium signals in transgenic mice. Surprisingly, we find cortical activity patterns consistent with indirect activation of auditory pathways rather than direct neuromodulation at the ultrasound focus. Ultrasound-induced activity is similar to that evoked by audible sound. Furthermore, both ultrasound and audible sound elicit motor responses consistent with a startle reflex, with both responses reduced by chemical deafening. These findings reveal an indirect auditory mechanism for ultrasound-induced cortical activity and movement requiring careful consideration in future development of ultrasonic neuromodulation as a tool in neuroscience research. Applying ultrasound to the brain leads to cortical activity patterns consistent with auditory pathway stimulation rather than direct neuromodulation. These findings reveal an indirect auditory mechanism for ultrasound-induced cortical and motor responses, requiring consideration in future development of ultrasonic neuromodulation.
Bibliographical noteFunding Information:
The authors thank Hubert Lim, Hongsun Guo, and Sangjin Yoo for helpful discussions and input on the manuscript, and members of the Shapiro and Tsao labs for assistance with experiments. This research was supported by NIH BRAIN Initiative grant R24MH106107 (Co-PIs D.Y.T. and M.G.S.) and the Howard Hughes Medical Institute (D.Y.T.). Related research in the Shapiro Laboratory is also supported by the Heritage Medical Research Institute and the Packard Fellowship in Science and Engineering .
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- auditory cortex
- cortical calcium imaging
- cross modal sensory interactions