Functional brain imaging research describing the neural basis for depression may enable better diagnoses and treatments. Studies of depressed patients should converge with findings from healthy subjects if they are to describe depression in terms of altered emotion processing. The current study aims to add to knowledge of emotion processing in healthy subjects by characterizing a neural network putatively disordered in depression. New techniques should examine the brain response to multiple task conditions, use functional connectivity analysis, and be thoroughly validated using healthy controls. Previous studies suggest 3 main regions of altered brain activity in depression. Activity in the amygdala correlates positively with depression symptoms. The orbitofrontal cortex is also more active in depression, but its activity correlates inversely with symptoms. This is speculated to represent a compensatory response to an initial functional lesion, possibly in the amygdala. Finally, activity at the pregenual cingulate cortex appears to predict response to drug treatment. In order to develop a paradigm to test the interactions between these regions, their hypothetical roles in emotion processing are drawn from human and animal research. This RO3 study proposes 2 tasks designed to evoke multiple states within these 3 regions, to improve the chance of observing differences in brain activation between controls and people with depression. In addition, functional connectivity will be measured by calculating the correlation of the activity in pairs of regions over time. These tasks will be tested in healthy controls to provide validated control data for future studies in subjects with depression.
3 specific aims will be accomplished.
Aim 1 : to identify a stimulus battery that elicits a reliable response in the amygdala, with pictures from the International Affective Picture System and the Ekman series of facial expressions.
Aim 2 : to test the working hypothesis that verbalizing emotional stimuli causes the orbitofrontal cortex to inhibit the amygdala.
Aim 3 : to test the working hypothesis that the pregenual cingulate cortex governs selection of salient emotional stimuli. ? ?
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