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The amygdala is a key regulator of vigilance and heightens attention toward threat. Its activity is boosted upon threat exposure and contributes to a neuroendocrine stress response via the hypothalamic–pituitary–adrenal (HPA) axis. Corticosteroids are known to control brain activity as well as HPA activity by providing negative feedback to the brain. However, it is unknown how corticosteroids affect the neural circuitry connected to the amygdala. Implementing a randomized, double-blind, placebo-controlled design, we here investigated the effects of 10-mg hydrocortisone on amygdala-centered functional connectivity patterns in men using resting state functional magnetic resonance imaging. Results showed generally decreased functional connectivity of the amygdala by corticosteroids. Hydrocortisone reduced “positive” functional coupling of the amygdala to brain regions involved in the initiation and maintenance of the stress response; the locus coeruleus, hypothalamus, and hippocampus. Furthermore, hydrocortisone reduced “negative” functional coupling of the amygdala to the middle frontal and temporal gyrus; brain regions known to be involved in executive control. A control analysis did not show significant corticosteroid modulation of visual cortex coupling, indicating that the amygdala decoupling was not reflecting a general reduction of network connectivity. These results suggest that corticosteroids may reduce amygdala’s impact on brain processing in the aftermath of stress in men.

Corticosteroid Induced Decoupling of the Amygdala in Men