Picture novelty attenuates semantic interference and modulates concomitant neural activity in the anterior cingulate cortex and the locus coeruleus

► We tested the influence of stimulus novelty on interference processing. ► Picture novelty attenuated typical behavioral conflict induced by incongruent words. ► Activity in the ACC and the locus coeruleus tracked conflict for familiar stimuli. ► Novelty benefited conflict-resolution in a bottom-up rather than top-down fashion.