Introduction: Synchronized oscillatory brain activity is considered a basis for flexible neuronal network communication. However, the causal role of inter-regional oscillatory phase relations in modulating signaling efficacy in cortical networks has not been directly demonstrated in humans so far. Aim: The current study addresses the causal role of transcranial alternating current stimulation (tACS)-induced oscillatory cross-network phase relations in modulating signaling efficacy across human cortical networks. Methods: To this end, concurrent tACS, transcranial magnetic stimulation (TMS), and electroencephalography (EEG) were employed to measure the modulation of excitability and signaling efficacy across cortical networks during externally induced neural oscillations. Theta oscillatory activity was introduced through tACS in two nodes of the human frontoparietal network: the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Six Hertz tACS was applied to the DLPFC and PPC simultaneously in an in-phase or antiphase manner. In addition, single-pulse TMS was administered over the DLPFC at four different phases of tACS and the propagation of TMS-evoked neuronal activity was measured with EEG. Results: We show that tACS-induced theta oscillations modulate TMS-evoked potentials (TEPs) in a phase-dependent manner, and that the induced oscillatory phase relation across the frontoparietal network affects the propagation of phase-dependent TEPs within as well as beyond the frontoparietal network. Conclusion: We show that the effect of tACS-induced phase relation across the frontoparietal network on signal transmission extends beyond the frontoparietal network. The results support a causal role of inter-nodal oscillatory phase synchrony in routing cortico-cortical information flow. Impact statement Theoretical models have proposed that phase relations of cross-network neural oscillations control communication efficacy across human cortical networks. The current study introduced concurrent transcranial alternating current stimulation-transcranial magnetic stimulation-electroencephalography (tACS-TMS-EEG) to experimentally study the theoretical framework. Dual-site in-phase or antiphase 6 Hz tACS was applied to the frontoparietal network. Synchronized tACS was shown to affect signaling within as well as beyond the targeted network. The study demonstrates how inter-regional oscillatory coherence supports the control of brain network signaling.
Keywords: effective connectivity; frontoparietal network; functional connectivity; phase synchrony; theta oscillations.