Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits

SummaryElectromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01°C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion.

► Transcranial pulsed ultrasound stimulates intact mouse brain circuits ► Ultrasound can stimulate intact cortex and hippocampus without exogenous factors ► Ultrasound consistently stimulates temporally precise TTX-sensitive brain activity ► Transcranial pulsed ultrasound confers an ∼2 mm lateral functional resolution