Previous, albeit correlative, findings have shown that the neural mechanisms underlying working memory critically require cross-structural and cross-frequency coupling mechanisms between theta and gamma neural oscillations. However, the direct causality between cross-frequency coupling and working memory performance remains to be demonstrated. Here we externally modulated the interaction of theta and gamma rhythms in the prefrontal cortex using novel cross-frequency protocols of transcranial alternating current stimulation to affect spatial working memory performance in humans. Enhancement of working memory performance and increase of global neocortical connectivity were observed when bursts of high gamma oscillations (80-100 Hz) coincided with the peaks of the theta waves, whereas superimposition on the trough of the theta wave and low gamma frequency protocols were ineffective. Thus, our results demonstrate the sensitivity of working memory performance and global neocortical connectivity to the phase and rhythm of the externally driven theta-gamma cross-frequency synchronization.

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Transcranial direct current stimulation (tDCS) has been proposed to be able to modulate different cognitive functions. However, recent meta‐analyses conclude that its efficacy is still in question. Recently, an increase in subjects’ propensity to mind‐wander has been reported as a consequence of anodal stimulation of the left dorsolateral prefrontal cortex (Axelrod et al., Proceedings of the National Academy of Sciences of the United States of America, 112, 2015). In addition, an independent group found a decrease in mind wandering after cathodal stimulation of the same region. These findings seem to indicate that high‐level cognitive processes such as mind wandering can reliably be influenced by non‐invasive brain stimulation. However, these previous studies used low sample sizes and are as such subject to concerns regarding the replicability of their findings. In this registered report, we implement a high‐powered replication of Axelrod et al. (2015) finding that mind‐wandering propensity can be increased by anodal tDCS. We used Bayesian statistics and a preregistered sequential‐sampling design resulting in a total sample size of N = 192 participants collected across three different laboratories. Our findings show support against a stimulation effect on self‐reported mind‐wandering scores. The effect was small, in the opposite direction as predicted and not reliably different from zero. Using a Bayes Factor specifically designed to test for replication success, we found strong evidence against a successful replication of the original study. Finally, even when combining data from both the original and replication studies, we could not find evidence for an effect of anodal stimulation. Our results underline the importance of designing studies with sufficient power to detect evidence for or against behavioural effects of non‐invasive brain stimulation techniques, preferentially using robust Bayesian statistics in preregistered reports.

Transcranial electrical stimulation (tES) is a neuromodulatory method with promising potential for basic research and as a therapeutic tool. The most explored type of tES is transcranial direct current stimulation (tDCS), but also transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) have been shown to affect cortical excitability, behavioral performance and brain activity. Although providing indirect measure of brain activity, functional magnetic resonance imaging (fMRI) can tell us more about the global effects of stimulation in the whole brain and what is more, on how it modulates functional interactions between brain regions, complementing what is known from electrophysiological methods such as measurement of motor evoked potentials. With this review, we aim to present the studies that have combined these techniques, the current approaches and discuss the results obtained so far.