Transcranial alternating current stimulation entrains single-neuron activity in the primate brain

Abstract

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. tES | tACS | transcranial alternating current stimulation | spike timing | phase-locking

Transcranial alternating current stimulation attenuates BOLD adaptation and increases functional connectivity

“…Current experimental evidence and computational models support two modes of action. The first is entrainment: alternating currents can entrain ongoing oscillations [9][10][11][12][13][14] and, given sufficiently long stimulation periods, this entrainment can outlast stimulation [15][16][17]. At the cellular level, entrainment is thought to result from the subthreshold modulation of the membrane potential by the weak intracranial electric field generated by the applied currents [2].…”

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

“…With regard to selectivity, we note even conventional tES easily reaches deep brain structures 11,14,43,44 with some deep selectivity achievable with High-Definition (HD) optimization 3,19 .…”

Biasing the perception of spoken words with tACS

“…In fact, concerns have been expressed recently about the efficacy of tDCS and tACS in directly modulating neural activity and behavior, in particular when applied currents are weak (~1-2 mA) (Liu et al 2018;Opitz et al 2016). At this current strength, effects on neural activity are observable, but may be restricted to temporal biasing of spikes and/or modulation of ongoing neural rhythms of similar frequency as the applied current (Liu et al 2018;Krause et al 2019). Our behavioral findings fit with these observations and point to an interesting role of sensory stimulation history on tACS efficacy, which should inspire further investigation into the constraints under which tACS modulates human behavior, and speech comprehension in particular.…”