Electrophysiological Source Imaging of Brain Networks Perturbed by Low-Intensity Transcranial Focused Ultrasound

Objective: Transcranial focused ultrasound (tFUS) has been introduced as a noninvasive neuromodulation technique with good spatial selectivity. We report an experimental investigation to detect noninvasive electrophysiological response induced by low-intensity tFUS in an in vivo animal model and perform electrophysiological source imaging (ESI) of tFUS-induced brain activity from noninvasive scalp EEG recordings. Methods: A single-element ultrasound transducer was used to generate low-intensity tFUS ( $\rm{I}_{\rm{spta}} ) and induce brain activation at multiple selected sites in an in vivo rat model. Up to 16 scalp electrodes were used to record tFUS-induced EEG. Event-related potentials were analyzed in time, frequency, and spatial domains. Current source distributions were estimated by ESI to reconstruct spatiotemporal distributions of brain activation induced by tFUS. Results: Neuronal activation was observed following low-intensity tFUS, as correlated to tFUS intensity and sonication duration. ESI revealed initial focal activation in cortical area corresponding to tFUS stimulation site and the activation propagating to surrounding areas over time. Conclusion: The present results demonstrate the feasibility of noninvasively recording brain electrophysiological response in vivo following low-intensity tFUS stimulation, and the feasibility of imaging spatiotemporal distributions of brain activation as induced by tFUS in vivo . Significance: The present approach may lead to a new means of imaging brain activity using tFUS perturbation and a closed-loop ESI-guided tFUS neuromodulation modality.