Transcranial Alternating Current and Random Noise Stimulation: Possible Mechanisms

Abstract

Background. Transcranial alternating current stimulation (tACS) is a relatively recent method suited to noninvasively modulate brain oscillations. Technically the method is similar but not identical to transcranial direct current stimulation (tDCS). While decades of research in animals and humans has revealed the main physiological mechanisms of tDCS, less is known about the physiological mechanisms of tACS. Method. Here, we review recent interdisciplinary research that has furthered our understanding of how tACS affects brain oscillations and by what means transcranial random noise stimulation (tRNS) that is a special form of tACS can modulate cortical functions. Results. Animal experiments have demonstrated in what way neurons react to invasively and transcranially applied alternating currents. Such findings are further supported by neural network simulations and knowledge from physics on entraining physical oscillators in the human brain. As a result, fine-grained models of the human skull and brain allow the prediction of the exact pattern of current flow during tDCS and tACS. Finally, recent studies on human physiology and behavior complete the picture of noninvasive modulation of brain oscillations. Conclusion. In future, the methods may be applicable in therapy of neurological and psychiatric disorders that are due to malfunctioning brain oscillations.

Figure 1

Assumed neural mechanism of tDCS. (a) Without tDCS, the resting potential of the cell is at −70 mV and an incoming excitatory postsynaptic potential (EPSP) arriving 100 ms after onset of the experiment does not reach the threshold for firing at −50 mV (dashed line). (b) If the neuron is close to an anode, the positive voltage from the anode will raise the resting potential towards a more positive voltage and the same EPSP will exceed the threshold and result in a neural spike. (c) If the neuron is close to a cathode, the negative voltage from the cathode will lower the resting potential towards a more negative voltage and the same EPSP will not exceed the threshold.

Figure 2

(a) Anisotropic finite element model for simulations of intracranial current flow. Stimulation electrodes are at the EEG electrode positions Cz and Oz of the international 10–20 system for electrode placement (red and blue, resp.). (b) Current density simulations reveal strongest current flow is in the posterior part of the brain underneath and between the stimulation electrodes. Reprinted with permission of the authors from [25].

Figure 3

Different montages result in different patterns of current densities. (a) tACS with two 4 × 1 electrode montages (high density, HD) was used in order to achieve a more focal current density. (b) Trying to achieve a similar pattern of current flow with conventional large electrodes results in a more widespread distribution of currents. Reprinted with permission of the authors from [27].

Figure 4

Translation of tACS intensity to intracranial voltage gradients allows a comparison to thresholds for eliciting spikes in animal research. The left axis represents tACS intensity. Neuling et al. [35] applied 1 mA intensity (peak-to-peak value: translates to a sine wave of 0.5 mA amplitude). In their FEM, they could show that this intensity results in a number of current densities in different parts of the brain with a maximum of 0.1 A/m² (axis: current density). The third axis represents the tissue resistivity of gray matter (tissue conductivity given on the left of the axis in brackets). Values in the range from 2.84 to 3.03 Ωm result in voltage gradients from 0.284 to 0.303 V/m being in the range of thresholds for neural firing or phase-locking (axis: voltage gradient). Note that for voltage gradients 1 mV/mm is equal to 1 V/m.

Figure 5

Theory of entrainment. If the brain is stimulated near its “Eigenfrequency,” that is, the individual alpha activity around 10 Hz, the EEG will synchronize to the frequency of the driving force (e.g., tACS). This is considered synchronization or entrainment of an oscillator by an external driving force and depicted in gray (1 : 1 region). If, however, the stimulation frequency is far from the “Eigenfrequency,” the EEG will be dominated by its “Eigenfrequency” (white regions of diagram). If the strength of the external driving force (tACS) increases, the synchronization regions will become wider in frequency. Due to this triangular shape the synchronization region is referred to as an Arnold tongue [51]. Synchronization can also happen at harmonics (N   ∗ Eigenfrequency) and subharmonics (Eigenfrequency/N) where N is an integer (1 : 2 and 2 : 1 show here). They do not need to have the same shape and width.