BACKGROUND: Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) is an established treatment regimen for major depressive disorder, but its instantaneous effects on neural excitability during and immediately after the stimulation remain unclear. This study aimed to investigate the hemodynamic response in the bilateral DLPFC during and immediately after iTBS and explored factors that may modulate iTBS-induced excitability. METHODS: We measured the prefrontal hemodynamic response before, during, and after iTBS using concurrent iTBS/functional near-infrared spectroscopy (fNIRS) in healthy participants across multiple sessions (3 to 11 visits, ≥48 hours apart). We investigated the moderating effect of several inter- and intra-individual variables. To this end, we analyzed the average change of oxygenated (HbO) and deoxygenated hemoglobin (HbR) in the stimulated and contralateral DLPFC and used generalized linear mixed models (GLMMs) to test for potential moderators. RESULTS: Twenty participants completed 157 concurrent iTBS/fNIRS sessions in total. HbR increased significantly during iTBS (0.247±0.032, p<
0.001) in the stimulated DLPFC, while the contralateral DLPFC showed significant decreases in HbR during (-0.046±0.017, p=0.024) and after the stimulation (-0.05±0.018, p=0.015). No significant change in HbO was observed. GLMM revealed that age (β=0.033, p=0.004), sex (β=-0.248, p=0.004), education years (β=-0.094, p<
0.001), the personality trait agreeableness (β=-0.013, p=0.005), and positive affect (β=-0.032, p=0.012) significantly influenced local HbR response during iTBS, and sex (β=0.305, p=0.012) significantly influenced local HbO response during iTBS. CONCLUSION: This study revealed a pronounced increase in HbR during iTBS in the stimulated DLPFC, alongside decreased HbR contralaterally both during and post-stimulation. Furthermore, our study highlights the importance of individual factors in understanding iTBS effects on cortical excitability.