Brain causality alterations in major depressive disorder treatment

Early-phase directional brain connectivity analysis reveals that pharmacological and neurostimulation treatments engage distinct neural oscillatory mechanisms within the first week. Elevated baseline right-dominant α-band causal transmission identifies patients unlikely to respond to pharmacological treatment, enabling alternative interventions before weeks of ineffective therapy. These phase-based causality metrics offer promising biomarkers for early treatment stratification and monitoring. The ability to distinguish treatment responders from nonresponders at baseline and detect treatment-specific changes within one week, before clinical response manifestation, suggests these causality measures capture early mechanistic alterations that could inform timely treatment optimization decisions. (EUDRACT Nos. 2005-000826-22 and 2015-001639-19, registered via www.clinicaltrialsregister.eu).