A stage-specific cascade of neural dysfunction emotional conflict processing in major depressive disorder

BACKGROUND: Persistent affective disturbance is a core, disabling feature of major depressive disorder (MDD), thought to stem from a dysfunctional interaction between emotional bias and cognitive control. However, the underlying neural dynamics are debated, with studies reporting both hyper- and hypoactivation. This study utilized high-temporal-resolution electroencephalogram (EEG) to resolve this discrepancy by examining distinct stages of emotional information processing. METHODS: We recruited 175 medication-free patients with MDD (Hamilton Depression Rating Scale-17 ≥ 14) and 101 healthy controls (HCs) who completed an emotional Stroop task while an EEG was recorded. We analyzed event-related potentials reflecting conflict monitoring (N250), inhibition (N450), and resolution (LSP) using a 2 (group) × 2 (valence) × 2 (congruency) analysis of variance. RESULTS: Results revealed a stage-specific neural cascade. Compared to HCs, the MDD group showed: (1) hypoactivation during initial conflict monitoring (attenuated N250 amplitude); (2) compensatory hyperactivation during conflict inhibition (a significant N450 interaction revealed generalized conflict activity in MDD, unlike the context-specific response in HCs); and (3) subsequent hypoactivation during conflict resolution (reduced LSP amplitude for negative stimuli). Crucially, altered N450 correlated with depression severity, and the entire neural cascade predicted behavioral performance. CONCLUSIONS: The apparent contradiction in the literature reflects a multistage process. MDD is characterized by an inefficient neural cascade: an initial deficit in conflict monitoring is followed by compensatory overactivation during inhibition, which ultimately proves insufficient, leading to impaired late-stage resolution. This temporally specific model advances our understanding of the pathophysiology of depression and identifies potential stage-specific targets for intervention.