Proceedings of the National Academy of Sciences | 2019
Transcranial alternating current stimulation entrains single-neuron activity in the primate brain
Abstract
Significance Neurostimulation is a common therapy for a variety of neurological disorders, but the most effective stimulation approaches are often highly invasive, requiring electrodes to be implanted deep within brain structures like the hippocampus and basal ganglia. Here, we show that transcranial electrical stimulation (tES), a neuromodulatory technique that uses electrodes placed outside the scalp, can also affect patterns of neural activity in these areas. We find that tES can reliably control the timing, but not the rate, of spikes in individual neurons. Because changes in spike timing are thought to play a key role in many brain functions, the data shown here suggest that tES may be a valuable tool for clinical and fundamental studies of the human brain. Spike timing is thought to play a critical role in neural computation and communication. Methods for adjusting spike timing are therefore of great interest to researchers and clinicians alike. Transcranial electrical stimulation (tES) is a noninvasive technique that uses weak electric fields to manipulate brain activity. Early results have suggested that this technique can improve subjects’ behavioral performance on a wide range of tasks and ameliorate some clinical conditions. Nevertheless, considerable skepticism remains about its efficacy, especially because the electric fields reaching the brain during tES are small, whereas the likelihood of indirect effects is large. Our understanding of its effects in humans is largely based on extrapolations from simple model systems and indirect measures of neural activity. As a result, fundamental questions remain about whether and how tES can influence neuronal activity in the human brain. Here, we demonstrate that tES, as typically applied to humans, affects the firing patterns of individual neurons in alert nonhuman primates, which are the best available animal model for the human brain. Specifically, tES consistently influences the timing, but not the rate, of spiking activity within the targeted brain region. Such effects are frequency- and location-specific and can reach deep brain structures; control experiments show that they cannot be explained by sensory stimulation or other indirect influences. These data thus provide a strong mechanistic rationale for the use of tES in humans and will help guide the development of future tES applications.