Targeting neural oscillations with transcranial alternating current stimulation

Abstract

Neural oscillations at the network level synchronize activity between regions and temporal scales. Transcranial alternating current stimulation (tACS), the delivery of low-amplitude electric current to the scalp, provides a tool for investigating the causal role of neural oscillations in cognition. The parameter space for tACS is vast and optimization is required in terms of temporal and spatial targeting. We review emerging techniques and suggest novel approaches that capitalize on the non-sinusoidal and transient nature of neural oscillations and leverage the flexibility provided by a customizable electrode montage and electrical waveform. The customizability and safety profile of tACS make it a promising tool for precision intervention in psychiatric illnesses.

Keywords: Aperiodic signal; Current density; Electric field; Peak frequency; Phase-amplitude coupling; Waveform shape; Weighted phase lag index.

Figure 1.. Neural oscillations as a mechanism for network coordination between regions and across spatiotemporal scales.

(A) Neural oscillations are defined as peaks above the aperiodic signal of the brain. By estimating and removing the aperiodic signal, the peak and amplitude of the resulting Gaussian distribution most accurately approximates the true periodic signal. (B) Neural oscillations often occur as a burst. A burst is characterized by the number of oscillation cycles which it comprises. The waveform shape of a neural oscillation in time domain is characterized by its rise-fall symmetry and peak-trough symmetry. (C) Interregional communication is estimated using functional connectivity. Genuine functional connections display a consistent phase lag. Weighted phase lag index capitalizes on this property and avoids the confound of volume conduction. (D) Phase-amplitude coupling (PAC) between two regions, or within the same region, estimates communication between a low-frequency oscillation and a high-frequency oscillation. The low-frequency oscillations represent activity at a larger spatiotemporal scale relative to the high-frequency oscillations.

Figure 2.. Spatial targeting using tACS.

(A) With two stimulation electrodes, the current enters one electrode and is extracted from the other, then the roles are reversed. The two regions under the stimulation electrodes are theorized to be put in anti-phase synchrony. (B) With three stimulation electrodes, two stimulation electrodes are delivered identical stimulation and a third larger stimulation electrode is used to retrieve the current. The third electrode is put in anti-phase synchrony with the two target electrodes. The current density and normalized electric field for the two-electrode montage in (A) are displayed in (D) and (E). (D) Inward current density in red is greatest under the anodal electrode and outward current density is greatest under the cathodal electrode [55]. (E) The normalized electric field is at its peak where the current direction inverts between the two stimulation electrodes [55]. (F) The discrepancy between inward/outward current density and normalized electric field is resolved by considering the electric field vectors.

Figure 3.. Temporal targeting that mimics endogenous neural activity.

(A) According to the Arnold tongue phenomenon, weaker stimulation is required to entrain neural oscillations when delivered at the same frequency as the endogenous oscillation (i). Whereas stimulation off the peak frequency is ineffective at a low amplitude (ii) or requires greater stimulation strength to entrain oscillations at the stimulation frequency (iii). Individual frequency targeting can be used to maximize entrainment or to shift the peak frequency of neural oscillations. (B) Stimulation can be delivered with a selected power spectrum (top) to generate unique waveforms (example in bottom). Transcranial random noise stimulation delivers a random waveform with equal power at all frequencies (i), or with a power distribution that approximates the aperiodic signal of the brain (ii). A random phase is used to generate unique waveforms. Stimulation can also be delivered with a chosen periodic and aperiodic signal. For example, an alpha frequency periodic waveform is mixed with an aperiodic signal that is flat in slope (iii) or steep in slope (iv). A random phase for the power distribution with a uniform phase for the bandwidth of the periodic signal is used to generate unique waveforms. (C) Cross-frequency tACS delivers a waveform that mimics phase-amplitude coupling with a high-frequency amplitude modulation at a particular phase of a low-frequency component. (D) Custom waveforms such as manipulating rise-decay symmetry can probe time-domain characteristics of neural oscillations. A previous study found that a steeper slope of direct electric stimulation increased spike rate [31].