Dynamic modulation of intrinsic functional connectivity by 1 transcranial direct current stimulation 2 Running title : tDCS and functional connectivity

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation 22 technique capable of modulating cortical excitability and thereby influencing behavior and 23 learning. Recent evidence suggests that bilateral tDCS over both primary sensorimotor cortices 24 (SM1) yields more prominent effects on motor performance in both healthy subjects and chronic 25 stroke patients than unilateral tDCS over SM1. To better characterize the underlying neural 26 mechanisms of this effect, we aimed to explore changes in resting-state functional connectivity 27 during both stimulation types. In a randomized single-blinded cross-over design, 12 healthy 28 subjects underwent functional magnetic resonance imaging at rest before, during and after 20 29 minutes of uni-, bilateral and sham tDCS stimulation over SM1. Eigenvector centrality mapping 30 (ECM) was used to investigate tDCS-induced changes in functional connectivity patterns across 31 the whole brain. Uniand bilateral tDCS over SM1 resulted in functional connectivity changes in 32 widespread brain areas as compared to sham both during and after stimulation. Whereas bilateral 33 tDCS predominantly modulated changes in primary and secondary motor as well as prefrontal 34 regions, unilateral tDCS affected prefrontal, parietal and cerebellar areas. No direct effect was 35 seen under the stimulating electrode in the unilateral condition. The time course of changes in 36 functional connectivity in the respective brain areas was non-linear and temporally dispersed. 37 These findings provide evidence towards a network-based understanding regarding the 38 underpinnings of specific tDCS interventions. 39