Frontolimbic response to negative feedback in clinical depression

Functional neuroimaging suggests that limbic regions of the medial frontal cortex may be abnormally active in individuals with depression. These regions, including the anterior cingulate cortex, are engaged in both action regulation, such as monitoring errors and conflict, and affect regulation, such as responding to pain. The authors examined whether clinically depressed subjects would show abnormal sensitivity of frontolimbic networks as they evaluated negative feedback. Depressed subjects and matched control subjects performed a video game in the laboratory as a 256-channel EEG was recorded. Speed of performance on each trial was graded with a feedback signal of A, C, or F. By 350 ms after the feedback signal, depressed subjects showed a larger medial frontal negativity for all feedback compared with control subjects with a particularly striking response to the F grade. This response was strongest for moderately depressed subjects and was attenuated for subjects who were more severely depressed. Localization analyses suggested that negative feedback engaged sources in the anterior cingulate and insular cortices. These results suggest that moderate depression may sensitize limbic networks to respond strongly to aversive events.