Transcranial focused ultrasound induces source localizable cortical activation in resting state humans when applied concurrently with transcranial electric stimulation

The effects of transcranial focused ultrasound (tFUS) on the human brain are poorly understood. Currently, the field is at odds with whether tFUS is subthreshold modulating the brain's excitability towards other stimuli, producing suprathreshold neural stimulation on its own, or if it even has a spatially specific non-auditory induced affect. Herein, we investigated the ability of tFUS, transcranial direct current stimulation (tDCS) and a novel combination of the two (transcranial electro-acoustic stimulation; tEAS) to evoke cortical target-location specific activity in 27 resting state humans with whole brain electroencephalography recordings. In none of the exogenous event related potentials did tFUS or tDCS result in location-specific activations. However, the co-modulatory combination of tEAS did, providing evidence that tFUS has a location-specific subthreshold modulatory effect. We propose a minimally modified Hodgkin Huxley model that explains our results and provides a unifying framework for the field-wide observed effects (or lack thereof) of tFUS.