The effects of priming theta burst stimulation with transcranial direct current stimulation on prefrontal cortex functioning: A double-blind sham-controlled study in healthy subjects

Non-invasive brain stimulation (NIBS) techniques such as transcranial direct current stimulation (tDCS) and theta-burst stimulation (TBS) have been increasingly used to target prefrontal brain regions, such as the dorsolateral prefrontal cortex (DLPFC), to optimize therapeutic outcomes. Recently, several innovative studies targeting the motor cortex have suggested that combining distinct NIBS techniques enhance changes in brain activity. Surprisingly, effects on the prefrontal areas are not systematically evaluated. Considering the role of the DLPFC in the pathogenesis of psychiatric and stress-related disorders, there is a lack of knowledge whether the combination of NIBS techniques targeting the DLPFC would result in changes in prefrontal functioning and mood related variables. In this double-blind, sham-controlled, within-subjects study, 68 healthy were submitted to two stimulation protocols targeting the DLPFC (active tDCS + active iTBS and sham tDCS + active iTBS), with one-week interval. The psychophysiological effects and safety of combined NIBS interventions over the DLPFC were evaluated. Moreover, the Maastricht Acute Stress Test (MAST) was used to activate the stress system and to examine the changes in prefrontal functioning following the two stimulation protocols. Results showed significant changes in autonomic activity (decreased heart rate, increased blood pressure and heart rate variability) directly following the stimulation but no differences between the two stimulation protocols were found. In both sessions, the confrontation with the stressor resulted in psychophysiological changes. However, these changes were not significantly different for the active tDCS + active iTBS compared to the sham tDCS + iTBS protocol. Overall, priming iTBS with tDCS did not result in significant changes in prefrontal functioning. Moreover, priming iTBS with active tDCS resulted in more subjective stress and was experienced as more painful compared to the sham tDCS + active iTBS protocol.