Cross-sectional and longitudinal analysis of prefrontal intermittent theta-burst stimulation-evoked hemodynamic responses in major depressive disorder

Prefrontal theta burst stimulation (TBS) - induced brain activation may offer insights into the therapeutic mechanisms underlying TBS. This study aimed to compare baseline TBS-induced prefrontal hemodynamic responses in individuals with major depressive disorder (MDD) and healthy controls (HCs), and to evaluate whether changes in stimulation-evoked responses are correlated with improvements in depressive symptoms following four weeks of daily TBS. Both MDD (n = 44; 70% females) and HCs (n = 45; 60% females) underwent a concurrent TBS/functional near-infrared spectroscopy (fNIRS) paradigm. MDD participants further received 20 sessions of intermittent TBS (iTBS) of the left dorsolateral prefrontal cortex, followed by post-treatment TBS/fNIRS measurements. TBS-evoked hemodynamic responses were analyzed using repeated-measures ANOVA and t-tests. Additionally, correlation analyses were conducted to assess the relationship between depressive symptom changes and prefrontal hemodynamic response changes following treatment. Significant increases in deoxyhemoglobin concentrations were observed both during and after TBS. However, no significant differences in TBS-induced hemoglobin responses were found between MDD participants and HCs. Notably, changes in individual TBS-induced hemodynamic responses after treatment significantly correlated with symptom reductions (r = -0.488, p = 0.037). These findings suggest that TBS-induced hemodynamic responses may reflect underlying neural changes that are functionally relevant to symptom improvement, highlighting their potential as neuroimaging markers for treatment monitoring in depression.