Extinction learning alters the neural representation of conditioned fear.

Extinction learning is a primary means by which conditioned associations to threats are controlled and is a model system for emotion dysregulation in anxiety disorders. Recent work has called for new approaches to track extinction-related changes in conditioned stimulus (CS) representations. We applied a multivariate analysis to previously -collected functional magnetic resonance imaging data on extinction learning, in which healthy young adult participants (N = 43; 21 males, 22 females) encountered dynamic snake and spider CSs while passively navigating 3D virtual environments. We used representational similarity analysis to compare voxel-wise activation t-statistic maps for the shock-reinforced CS (CS+) from the late phase of fear acquisition to the early and late phases of extinction learning within subjects. These patterns became more dissimilar from early to late extinction in a priori regions of interest: subgenual and dorsal anterior cingulate gyrus, amygdala and hippocampus. A whole-brain searchlight analysis revealed similar findings in the insula, mid-cingulate cortex, ventrolateral prefrontal cortex, somatosensory cortex, cerebellum, and visual cortex. High state anxiety attenuated extinction-related changes to the CS+ patterning in the amygdala, which suggests an enduring threat representation. None of these effects generalized to an unreinforced control cue, nor were they evident in traditional univariate analyses. Our approach extends previous neuroimaging work by emphasizing how evoked neural patterns change from late acquisition through phases of extinction learning, including those in brain regions not traditionally implicated in animal models. Finally, the findings provide additional support for a role of the amygdala in anxiety-related persistence of conditioned fears.