Transcranial stimulation of alpha oscillations upregulates the default mode network

Abstract The default mode network (DMN) is the most prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly, alpha (8-12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition (HD) alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous EEG-fMRI, we demonstrated that α-tACS (vs. sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can upregulate the DMN further highlights an effective non-invasive intervention to normalize DMN functioning in various disorders. Significance Statement In the brain’s functional organization, the default mode network (DMN) represents a key architecture, whose dysregulation is involved in a host of major neuropsychiatric disorders. However, insights into the regulation of the DMN remain scarce. Through neural synchrony, the alpha-frequency oscillation represents another key underpinning of the brain’s organization and is thought to share an inherent interdependence with the DMN. Here, we demonstrated that transcranial alternating current stimulation of alpha oscillations (α-tACS) not only augmented alpha activity but also strengthened connectivity of the DMN, with the former serving as a mediator of the latter. These findings reveal that alpha oscillations can support DMN functioning. In addition, they identify an effective non-invasive approach to regulate the DMN via α-tACS.