Intermittent theta burst stimulation at personalized targets reduces the functional connectivity of the default mode network in healthy subjects

Abstract

Understanding the mechanisms by which transcranial magnetic stimulation protocols exert changes in the default mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. A full session (3000 pulses) of 10 Hz repetitive transcranial magnetic stimulation (HF-rTMS) reduces the functional connectivity (FC) of the DMN and the subgenual anterior cingulate cortex but current understanding of the effects of a single session of intermittent theta burst stimulation (iTBS) on the DMN in healthy subjects is limited. To reduce the effects of inter-individual variability in functional architectures, we used a novel personalized target selection approach based on each subjects resting state fMRI for an unprecedented investigation into the effects of a single session (1800 pulses) of iTBS over the DMN in healthy controls. 26 healthy subjects participated in a double-blind, crossover, sham-controlled study. After iTBS to the personalized left dorsolateral prefrontal cortex (DLPFC) targets, we investigated the time lapse of effects in the DMN and its relationship to the harm avoidance (HA) personality trait measure (Temperament and Character Inventory/TCI). Approx. 25-30 minutes after stimulation, we observed reduced FC between the DMN and the rostral anterior cingulate cortex (rACC). About 45 minutes after stimulation the FC of rACC strongly decreased further, as did the FC of right anterior insula (rAI) with the DMN. We also report a positive correlation between the FC decrease in the rACC and the HA domain of TCI. Our results show how iTBS at personalized left-DLPFC targets reduces the FC between DMN and the rACC and rAI, regions typically described as nodes of the salience network. We find that HA scores can potentially predict iTBS response, as has been observed for HF-rTMS.