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

BACKGROUND: 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. METHODS: 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: 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. CONCLUSION: Our findings suggest that TBS might modulate ALFF, highlighting the need to further investigate factors such as rumination.