Acute prefrontal hemodynamic responses to intermittent theta burst stimulation correlate with current depression and episode recurrence: A cross-sectional study

Background: Mounting evidence has indicated that multiple major depressive disorder (MDD) episodes are correlated with brain morphometric changes that confer an increased recurrence risk. Functional abnormalities underlying this recurrent vulnerability remain underexplored. Acute neuroplastic responses to repetitive transcranial magnetic stimulation hold promise to identify such functional alterations. Methods: This study involved 121 adults, including 39 individuals with current MDD, 41 individuals with MDD in remission, and 41 healthy controls. Cross-sectional changes in hemodynamic responses and functional connectivity induced by a single session of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (dlPFC) were measured using simultaneous functional near-infrared spectroscopy and analyzed with linear mixed models. Hierarchical regression examined the relationships between the number of prior depressive episodes and observed functional changes in patient cohorts. Results: Stimulation instantly elevated deoxyhemoglobin levels in the stimulated dlPFC across all participants, with greater increases in patient cohorts versus controls, demonstrating a persistent disease effect regardless of prior episodes or remitted state. Poststimulation increases in oxyhemoglobin concentration were current depression-dependent and associated with multiple episodes in remitted patients. Prefrontal networks were characterized by a transient reduction in global node degree during stimulation in all groups. Conclusions: Our findings align with clinical and preclinical evidence linking disrupted neurovascular function in the prefrontal cortex to depression pathophysiology. Poststimulation responses in the stimulated dlPFC, reflecting the current state and multiple prior episodes, show potential for aiding in differential diagnosis and indicating depression vulnerability. Longitudinal studies are needed to determine whether such neurological dysfunctions represent disease progression or a vulnerability biomarker.