BackgroundMajor depressive disorder (MDD) is characterized by strong emotional dysregulation. Mechanisms driving the negative affect in depression may be fast processes existing on an unconscious level. MethodsA priming task was conducted using simultaneous EEG-fMRI measurement involving presentation of facial expressions (happy, sad, neutral) to examine the neurophysiological pathway of biased unconscious emotion processing in MDD. Priming prior to a target emotion created unconscious (16.7 ms primer) and conscious (150 ms primer) trials. A large sample of N = 126 was recruited, containing healthy controls (HC; n = 66; 37 women) and MDD (n = 60; 31 women). ResultsHC showed a shorter reaction time in happy, but not in sad or neutral trials compared to MDD. N170 amplitudes were lower in trials with unconscious compared to conscious primer presentation. N170 amplitudes correlated with cortical (right fusiform gyrus (FFG), right middle temporal gyrus, right inferior temporal gyrus, left supplementary motor area, right middle frontal gyrus) and subcortical brain regions (right amygdala). The strength of N170 and brain activity correlation increased when the stimulus was consciously presented. Presented emotions did not affect the correlation of N170 values and brain activity. ConclusionsOur findings show that MDD may exhibit biased emotion regulation abilities at a behavioral and neurophysiological level. Face-sensitive event-related potentials demonstrate a correlation with heightened brain activity in regions associated with both face recognition (FFG) and emotion processing (amygdala). These findings are evident in both MDD and HC, with lower effect sizes in MDD indicating reduced emotion recognition and processing abilities.