PT - JOURNAL ARTICLE AU - Turi, Zsolt AU - Mittner, Matthias AU - Lehr, Albert AU - Bürger, Hannah AU - Antal, Andrea AU - Paulus, Walter TI - θ-γ Cross-Frequency Transcranial Alternating Current Stimulation over the Trough Impairs Cognitive Control AID - 10.1523/ENEURO.0126-20.2020 DP - 2020 Sep 01 TA - eneuro PG - ENEURO.0126-20.2020 VI - 7 IP - 5 4099 - http://www.eneuro.org/content/7/5/ENEURO.0126-20.2020.short 4100 - http://www.eneuro.org/content/7/5/ENEURO.0126-20.2020.full SO - eNeuro2020 Sep 01; 7 AB - Cognitive control is a mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the θ band and θ-γ cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. However, to date, the behavioral consequences of different forms of θ-γ CFC remain elusive. Here, we studied the behavioral effects of the θ-γ 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 γ tACS was coupled to 4-Hz θ tACS. Specifically, in two of the active conditions, short γ bursts were coupled to the delivered θ cycle to coincide with either its peaks or troughs. In the third active condition, the phase of a θ cycle modulated the amplitude of the γ 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 θ-γ CFC.