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The current study uses functional magnetic resonance imaging (fMRI) to examine whether regulating negative bias to stigmatized individuals has a unique neural activity profile from general emotion regulation. Participants were presented with images of stigmatized (e.g. homeless people) or non-stigmatized (e.g. a man holding a gun) social targets while undergoing fMRI and were asked either to maintain or regulate their emotional response. Their implicit bias toward these stigmatized group members was also measured. Analyses were conducted in both, an event-related fashion, considering the event to be the onset of regulation, and in a blocked-design fashion, considering the sustained activity throughout the 8-s regulatory period. In the event-related (onset) analyses, participants showed more activity throughout the prefrontal cortex when initiating a regulatory response to stigmatized as compared with non-stigmatized images. This neural activity was positively correlated with their implicit bias. Interestingly, in the block (sustained) analyses, general emotion regulation elicited a more widespread pattern of neural activity as compared with stigma regulation. This activity was largely posterior, suggesting that general emotion regulation may engage more visuo-spatial processing as compared with stigma regulation. These findings suggest that regulating negative affect toward stigmatized targets may occur relatively more quickly than regulating negative affect toward non-stigmatized targets.