Effects of weak transcranial alternating current stimulation on brain activity-a review of known mechanisms from animal studies

Abstract

Rhythmic neuronal activity is ubiquitous in the human brain. These rhythms originate from a variety of different network mechanisms, which give rise to a wide-ranging spectrum of oscillation frequencies. In the last few years an increasing number of clinical research studies have explored transcranial alternating current stimulation (tACS) with weak current as a tool for affecting brain function. The premise of these interventions is that tACS will interact with ongoing brain oscillations. However, the exact mechanisms by which weak currents could affect neuronal oscillations at different frequency bands are not well known and this, in turn, limits the rational optimization of human experiments. Here we review the available in vitro and in vivo animal studies that attempt to provide mechanistic explanations. The findings can be summarized into a few generic principles, such as periodic modulation of excitability, shifts in spike timing, modulation of firing rate, and shifts in the balance of excitation and inhibition. These effects result from weak but simultaneous polarization of a large number of neurons. Whether this can lead to an entrainment or a modulation of brain oscillations, or whether AC currents have no effect at all, depends entirely on the specific dynamic that gives rise to the different brain rhythms, as discussed here for slow wave oscillations (∼1 Hz) and gamma oscillations (∼30 Hz). We conclude with suggestions for further experiments to investigate the role of AC stimulation for other physiologically relevant brain rhythms.

Keywords: animal models; electroencephalogram (EEG); entrainment; gamma; oscillations; slow wave; transcranial alternating current stimulation (tACS); transcranial direct current stimulation (tDCS).

Figure 1

Effects of AC stimulation on single and network of neurons. (A) Schematic of the effects of AC stimulation on resting neurons. Sinusoidal electrical stimulation (AC, red lines) sinusoidally modulates the membrane voltage (black lines). The membrane polarization increases with increasing stimulation amplitude (A, 2A, 3A) but decreases with increasing stimulation frequency (F, 2F, 4F). (B) Examples of possible effects of weak AC stimulation on oscillations. AC stimulation can entrain the oscillations by shifting their phase (left) or modulate its power at the stimulation frequency (right). (C) Schematics of the effects of AC stimulation on network of neurons. While the effects of electrical stimulation on single neurons are small (left), synaptically connected neurons can provide feedback that amplifies the effects of stimulation (center). However, active neurons create network oscillations, usually set by the level of activity of excitatory and inhibitory neurons (triangle and circles, respectively). In this case, the effects of stimulation cannot a priori always be determined (right). (D) Summary of the known effects of weak AC stimulation on gamma oscillations. AC fields can entrain spiking activity at very low intensities (green), while low-frequency stimulation modulates the power of gamma oscillations (yellow). Gamma oscillations can be entrained (dashed lines) by using frequencies close to the endogenous one or double that frequency (increase in frequency, red, or decrease in frequency, blue). Frequencies close to the stimulation frequency but higher intensity induce pacing at half of the stimulation frequency (cyan). Color gradients indicate size of the effects. Frequencies that do not match the endogenous frequency, for example, can still affect the oscillations if the stimulation amplitude is increased. The figure is adapted from Reato et al. (2010). (E) Schematics of the in vitro and in vivo animal studies applying AC (sinusoidal) stimulation on oscillatory rhythms. The main frequency of the endogenous oscillations of interest (vertical axis) and the stimulation frequencies applied in the different studies (horizontal axis) demonstrate the limited range of neural rhythms that have been described in the animal literature. Colors indicate frequency bands. Also note the log-scale axes.