Ultrasonic Neuromodulation Causes Widespread Cortical Activation via an Indirect Auditory Mechanism

Neuron. 2018 Jun 6;98(5):1031-1041.e5. doi: 10.1016/j.neuron.2018.05.009. Epub 2018 May 24.


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.

Keywords: auditory cortex; cortical calcium imaging; cross modal sensory interactions; neuromodulation; ultrasound.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Cortex / diagnostic imaging
  • Auditory Cortex / radiation effects*
  • Auditory Pathways / diagnostic imaging
  • Auditory Pathways / radiation effects*
  • Brain / diagnostic imaging
  • Brain / radiation effects
  • Calcium Signaling
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / radiation effects
  • Electrophysiological Phenomena / radiation effects
  • Mice
  • Mice, Transgenic
  • Motor Activity / radiation effects
  • Optical Imaging
  • Reflex, Startle / radiation effects*
  • Sound*
  • Ultrasonic Waves*