Theta-gamma cross-frequency transcranial alternating current stimulation over the trough impairs cognitive control

Cognitive control is a hypothetical 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. Yet, 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. Using a double-blind, randomized, repeated measures study design, 24 healthy participants were subjected to three main, active CFC-tACS protocols: Short gamma frequency bursts (80 Hz) were coupled to an ongoing theta cycle (4 Hz) to coincide with either the peaks or the troughs of the theta wave. In a third condition, the amplitude of the gamma oscillation was modulated by the phase of a theta cycle. In the fourth, control protocol, gamma was continuously superimposed over the theta cycle, therefore lacking any phase-specificity in the CFC. During the 20-minute stimulations, the participants performed a Go/NoGo monetary reward- and punishment-based instrumental learning task. A Bayesian hierarchical logistic regression analysis revealed that CFC-tACS over peak had no effects on the behavioral performance, whereas CFC-tACS over trough 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.