Focused Epicranial Brain Stimulation by Spatial Sculpting of Pulsed Electric Fields Using High Density Electrode Arrays

Abstract Transcranial electrical neuromodulation of the central nervous system is used as a non‐invasive method to induce neural and behavioral responses, yet targeted non‐invasive electrical stimulation of the brain with high spatial resolution remains elusive. This work demonstrates a focused, steerable, high‐density epicranial current stimulation (HD‐ECS) approach to evoke neural activity. Custom‐designed high‐density (HD) flexible surface electrode arrays are employed to apply high‐resolution pulsed electric currents through skull to achieve localized stimulation of the intact mouse brain. The stimulation pattern is steered in real time without physical movement of the electrodes. Steerability and focality are validated at the behavioral, physiological, and cellular levels using motor evoked potentials (MEPs), intracortical recording, and c‐fos immunostaining. Whisker movement is also demonstrated to further corroborate the selectivity and steerability. Safety characterization confirmed no significant tissue damage following repetitive stimulation. This method can be used to design novel therapeutics and implement next‐generation brain interfaces.