θ - γ Cross-Frequency Transcranial Alternating Current Stimulation over the Trough Impairs Cognitive Control

Cognitive control is a mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the theta band and theta - gamma cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. However, to date, the behavioral consequences of different forms of theta - gamma CFC remain elusive. Here, we studied the behavioral effects of the theta - gamma CFC via transcranial alternating current stimulation (tACS) designed to stimulate the frontal and cingulate cortices in humans. Using a double-blind, randomized, repeated measures study design, 24 healthy participants were subjected to three active and one control CFC-tACS conditions. In the active conditions, 80-Hz gamma tACS was coupled to 4-Hz theta tACS. Specifically, in two of the active conditions, short gamma bursts were coupled to the delivered theta cycle to coincide with either its peaks or troughs. In the third active condition, the phase of a theta cycle modulated the amplitude of the theta oscillation. In the fourth, control protocol, 80-Hz tACS was continuously superimposed over the 4-Hz tACS, therefore lacking any phase specificity in the CFC. During the 20 min of stimulation, the participants performed a Go/NoGo monetary reward-based and punishment-based instrumental learning task. A Bayesian hierarchical logistic regression analysis revealed that relative to the control, the peak-coupled tACS had no effects on the behavioral performance, whereas the trough-coupled tACS and, to a lesser extent, amplitude-modulated tACS reduced performance in conflicting trials. Our results suggest that cognitive control depends on the phase specificity of the theta - gamma CFC.