Affective context interferes with cognitive control in unipolar depression: An fMRI investigation

Background: Unipolar major depressive disorder (MDD) is characterized by aberrant amygdala responses to sad stimuli and poor cognitive control, but file interactive effects of these impairments are poorly understood. Aim: To evaluate brain activation in MDD in response to cognitive control stimuli embedded within sad and neutral contexts. Method: Fourteen adults with MDD and fifteen matched controls participated in a mixed block/event-related functional magnetic resonance imaging (fMRI) task that presented oddball target stimuli embedded within blocks of sad or neutral images. Results: Target events activated similar prefrontal brain regions in both groups. However, responses to target events embedded within blocks of emotional images revealed a clear group dissociation. During neutral blocks, the control group demonstrated greater activation to targets in the midfrontal gyrus and anterior cingulate relative to the MDD group, replicating previous findings of prefrontal hypoactivation in MDD samples to cognitive control stimuli. However, doting sad blocks, the MDD group demonstrated greater activation in a number of prefrontal regions, including the mid-, interior, and orbito-frontal gyri and the anterior cingulate, suggesting that relatively more prefrontal brain activation was required to disengage from the sad images to respond to the target events. Limitations: A larger sample size would have provided greater statistical power, and more standardized stimuli would have increased external validity. Conclusions: This double dissociation of prefrontal responses to target events embedded within neutral and sad context suggests that M-DD impacts not only responses to affective events, but extends to other cognitive processes carried out in die context of affective engagement. This implies that emotional reactivity to sad events in MDD may impact functioning more broadly than previously understood. (c) 2008 Elsevier B.V. All rights reserved.