Repeated theta burst stimulation of the right ventrolateral prefrontal cortex reveals strong habituation in the context of stress and rumination

Prefrontal hypoactivation under stress has been consistently observed in individuals with high trait rumination and in patients with depression. However, no study has yet investigated the mechanisms of modulating activity of the Ventrolateral Prefrontal Cortex (VLPFC) by using excitatory and inhibitory Theta Burst Stimulation (TBS) in this context. To address this, we recruited 89 healthy participants (44 low trait ruminators and 45 high trait ruminators) who attended two lab sessions, each including stress induction via the Trier Social Stress Test (TSST). Participants received either excitatory intermittent TBS (iTBS) or inhibitory continuous TBS (cTBS). One session involved active TBS, while the other used sham TBS (sTBS), with the order randomized and balanced across stimulation conditions and groups. In high ruminators, we observed a significant impact of iTBS in the hypothesized direction when considering cortical oxygenation in the right VLPFC. We found higher subjective stress following iTBS and cTBS compared to sTBS during recovery of the TSST but only at the first appointment. No stimulation-dependent effects were found for other measures (state rumination, positive and negative affect, and heart rates). In our discussion, we draw conclusions concerning repeated-measures designs in TBS-studies.