Direct effects of transcranial electric stimulation on brain circuits in rats and humans

TLDR

Transcranial electric stimulation can modulate brain activity, but the in‑vivo parameters required to target local circuits are not yet defined. The study aims to develop an intersectional short‑pulse stimulation method that delivers high current to the brain while keeping scalp charge density and sensation low. The authors implemented this method by applying short, high‑intensity pulses that penetrate soft tissue and skull to achieve a voltage gradient of at least 1 mV/mm. Their data show that scalp‑applied currents are largely attenuated, that ≥1 mV/mm is needed to affect neuronal spiking, and that the new method produces regionally specific, instantaneous modulation of neuronal circuits in rodents and humans, including changes in EEG alpha amplitude.

Abstract

Transcranial electric stimulation is a non-invasive tool that can influence brain activity; however, the parameters necessary to affect local circuits in vivo remain to be explored. Here, we report that in rodents and human cadaver brains, ~75% of scalp-applied currents are attenuated by soft tissue and skull. Using intracellular and extracellular recordings in rats, we find that at least 1 mV/mm voltage gradient is necessary to affect neuronal spiking and subthreshold currents. We designed an 'intersectional short pulse' stimulation method to inject sufficiently high current intensities into the brain, while keeping the charge density and sensation on the scalp surface relatively low. We verify the regional specificity of this novel method in rodents; in humans, we demonstrate how it affects the amplitude of simultaneously recorded EEG alpha waves. Our combined results establish that neuronal circuits are instantaneously affected by intensity currents that are higher than those used in conventional protocols.