Experimental evaluation of an integrated focused ultrasound and electroencephalography approach for developing activation-informed neuroimaging

• We measured the electrophysiological activity in rat cortex elicited by ultrasound. • Electrophysiology can be precisely probed with ultrasound and measured with EEG. • A full spectrum of activity can be transcranially elicited and noninvasively recorded. • Ultrasound-EEG approach is useful for activation-informed neuroimaging. We experimentally evaluated the possibility of using an integrated focused ultrasound (FUS) - electroencephalography (EEG) approach to develop activation-informed neuroimaging for human functional brain mapping, enhancing the power of conventional approaches based solely on recording methods. A brief beam of FUS (50 μs, 4.0 MHz) with a focal transverse profile diameter of 0.4 mm determined in water was applied to the barrel cortex of rat in vivo on the dura, skull and scalp and evoked activity was recorded with EEG. We found using a laminar depth profile analysis and specific channel blockers that the stimulation within a safe pressure range could directly evoke a presynaptic spike (∼1 ms) in layer IV, followed by postsynaptic spikes (2.5-7 ms) in layer V and an excitatory wave (8-12 ms), both regulated by fast inhibition, and a major robust excitatory wave (20-30 ms) regulated by slow inhibition. Stimulus artifact was <1 ms, much shorter than for transcranial magnetic stimulation. All components were reliably detected from the scalp, skull, and dura using the 4 MHz and 2.2 MHz transducers. Thus, the FUS-EEG approach is capable of activating neurons transcranially and noninvasively recording a rich spectrum of excitatory and inhibitory activity starting immediately after stimulation. These characteristics can advance neuroimaging since this approach can identify normal electrophysiology and pathophysiology in known locations anywhere in the brain with precise timing and could possibly enhance the conventional approaches by validating and improving their spatial and temporal accuracy of localization.