Behavioral and Neural Mechanisms of Overgeneralization in Anxiety.

Overgeneralization of dangerous stimuli is a possible etiological account for anxiety disorders, yet the underlying behavioral and neural origins remain vague. Specifically, it is unclear whether this is a choice behavior in an unsafe environment ("better safe than sorry") or also a fundamental change in how the stimulus is perceived. We show that anxiety patients have wider generalization for loss-conditioned tone when compared to controls and do so even in a safe context that requires a different behavioral policy. Moreover, patients overgeneralized for gain-conditioned tone as well. Imaging (fMRI) revealed that in anxiety only, activations during conditioning in the dACC and the putamen were correlated with later overgeneralization of loss and gain, respectively, whereas valence distinction in the amygdala and hippocampus during conditioning mediated the difference between loss and gain generalization. During generalization itself, neural discrimination based on multivoxel patterns in auditory cortex and amygdala revealed specific stimulus-related plasticity. Our results suggest that overgeneralization in anxiety has perceptual origins and involves affective modulation of stimulus representations in primary cortices and amygdala.