Preconditioning Prefrontal Connectivity Using Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation

Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been shown to modulate functional connectivity. Their specific effects seem to be dependent on the pre-existing neuronal state. We aimed to precondition frontal networks using tDCS and subsequently stimulate the left dorsolateral prefrontal cortex (lDLPFC) using TMS. Thirty healthy participants underwent either excitatory, inhibitory or sham tDCS for 10 min, as well as an excitatory intermittent theta burst (iTBS) protocol (600 pulses in 190 s, 20 x 2 s trains), applied over the lDLPFC at 90% of the individual resting motor threshold. Functional connectivity was measured in three task-free, 10-min-long baseline resting state fMRI sessions, immediately before and after tDCS, as well as after iTBS. Connectivity analyses between stimulation site and all other brain voxels, contrasting the interaction effect between the experimental tDCS groups (excitatory vs inhibitory) and the repeated measure (post tDCS vs. post TMS), revealed significantly affected voxels bilaterally in the anterior cingulate and paracingulate gyri, the caudate nuclei, the insula and operculum cortices, as well as the Heschl’s gyrus. ROI-to-ROI analyses additionally showed temporo-parietal-striatal and temporo-parietal-fronto-cingulate differences between the anodal and cathodal group post tDCS, as well as striatal-temporo-parietal anodal-cathodal differences and frontostriatal cathodal-sham group differences post TMS. Excitatory iTBS to a tDCS-inhibited lDLPFC yielded stronger functional connectivity to various areas, as compared to excitatory iTBS to a tDCS-enhanced prefrontal cortex. Results demonstrate complex, whole-brain stimulation effects, most-likely facilitated by cortical homeostatic control mechanisms, as well as the feasibility of using tDCS to modulate TMS effects.