Dissecting the anticipation of aversion reveals dissociable neural networks

The anticipation of future adversity confers adaptive benefits by en-gaging a suite of preparatory mechanisms, but this process can also be deleterious when carried out in excess. Neuroscientific investigations have largely treated anticipation as a unitary process, but we show here using functional magnetic resonance imaging that distinct stages of aversive anticipation are supported by disso-ciable neural mechanisms. Immediate anticipatory responses were observed in regions associated with threat detection and early pro-cessing of predictive cues, including the orbitofrontal cortex and pregenual anterior cingulate cortex, as well as the amygdala for individuals with elevated anxiety symptoms. Sustained anticipatory activity was observed in the forebrain/bed nucleus of the stria ter-minalis, anterior insula, anterior mid-cingulate cortex (aMCC), and midbrain/periaqueductal gray, regions associated with anxiety, in-teroception, and defensive behavior. The aMCC showed increased functional coupling with the midbrain during sustained anticipation of aversion, highlighting a circuit critical for the expression of pre-paratory fear responses. These data implicate distinct sets of regions that are active during different temporal stages of antici-pation, and provide insight into how the human brain faces the future both adaptively and maladaptively