The relationship of perceptual discrimination to neural mechanisms of fear generalization.

The generalization of conditioned fear responses has been shown to decrease as a function of perceptual similarity. However, generalization may also extend beyond the perceptual discrimination threshold, ostensibly due to contributions from processes other than perception. Currently the neural mechanisms that mediate perceptual and non-perceptual aspects of fear generalization are unclear. To investigate this question, we conducted a Pavlovian fear conditioning and generalization experiment, collecting functional magnetic resonance imaging (fMRI), skin conductance and explicit shock likelihood ratings, in 37 healthy subjects. Face stimuli were initially paired (CS+) or not paired (CS) with an electrical shock. During the generalization phase, responses were measured to the CS+, CS and a range of CS + -toCS morphs (generalization stimuli), selected for each participant based on that participant's discrimination ability. Across multiple measurements, we found that fear generalization responses were limited to stimuli that could not be distinguished from the CS + stimulus, thus following a gradient closely linked to perceptual discriminability. These measurements, which were correlated with one another, included skin conductance responses, behavioral ratings, and fMRI responses of anterior insula and superior frontal gyrus. In contrast, responses in areas of the default network, including the posterior cingulate gyrus, angular gyrus and hippocampus, showed a negative generalization function extending to stimuli that were more likely to be distinguished from the CS+. In addition, the generalization gradients of the anterior insula and the behavioral ratings showed some evidence for extension beyond perceptual limits. Taken together, these results suggest that distinct brain areas are involved in perceptual and non-perceptual components of fear generalization.