Theta Burst Stimulation Prior to Stress Exposure Alters Amplitude of Low-Frequency Fluctuations

The Amplitude of Low-Frequency Fluctuations (ALFF) serves as a marker of spontaneous neural activity, with previous research showing increased ALFF during rumination induction. However, it remains unclear whether Theta Burst Stimulation (TBS) might be able to modulate ALFF. In two studies, we applied intermittent (iTBS) and continuous (cTBS) protocols to the left Dorsolateral Prefrontal Cortex (DLPFC; study 1) and right Ventrolateral Prefrontal Cortex (VLPFC; study 2) prior to the Trier Social Stress Test (TSST). Neural activity was assessed using functional near-infrared spectroscopy (fNIRS), an optical imaging technique measuring cortical oxygenation, from which ALFF was derived. In both studies (study 1: 88; study 2: 89) low and high trait ruminators were recruited. Each participant underwent both active (iTBS or cTBS) and sham TBS (sTBS) in a randomized, counterbalanced double-blind design. We fitted rmANOVAs examining the effects of time, trait rumination, TBS-condition and Regions of Interest (ROI) for each stimulation target. Results indicated stress-related increases in ALFF across all ROIs, including the DLPFC, VLPFC, and Somatosensory Association Cortex. We found partial evidence for TBS-induced modulation of frontal ALFF, however blinding was partly unsuccessful: In study 2, targeting the right VLPFC, both cTBS and sTBS were associated with increases in ALFF from the pre-TSST resting-state to the TSST, followed by decreases from the TSST to the post-TSST resting-state. This effect was absent following iTBS and when reanalyzing effects using Percent ALFF. Our findings suggest that TBS might modulate ALFF, highlighting the need to further investigate factors such as rumination. • TBS effects on ALFF were examined during stress using fNIRS and the TSST • Data of two studies employing sTBS, cTBS or iTBS to the lDLPFC or rVLPFC was merged • Stress induction generally increased ALFF across frontal and somatosensory regions • Targeting the rVLPFC, cTBS and sTBS increased ALFF during stress while iTBS did not