Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats

TLDR

Low intensity electric fields have been suggested to affect ongoing neuronal activity in vitro and in humans, but the physiological mechanism by which weak fields interact with intact brain activity remains unclear. We propose that transcranial electric stimulation (TES) in chronic preparations could be used for experimental and therapeutic control of brain activity. We recorded in vivo extracellular and intracellular activity from the neocortex and hippocampus of anesthetized and behaving rats while applying sinusoidal electric fields (0.8–1.7 Hz) generated by skull or dura surface electrodes. TES reliably entrained neurons across widespread cortical areas, including the hippocampus, with phase‑locked neuron percentages increasing with stimulus intensity and behavioral state, and even a 1 mV/mm voltage gradient was sufficient to bias spiking; intracellular recordings showed both spiking and subthreshold activity were jointly influenced by TES fields and network activity.

Abstract

Low intensity electric fields have been suggested to affect the ongoing neuronal activity in vitro and in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performed in vivo extracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity.