Neurobehavioral mechanisms of human fear generalization

While much research has elucidated the neurobiology of fear learning, the neural systems supporting the generalization of learned fear are unknown. Using functional magnetic resonance imaging (fMRI), we show that regions involved in the acquisition of fear support the generalization of fear to stimuli that are similar to a learned threat, but vary in fear intensity value. Behaviorally, subjects retrospectively misidentified a learned threat as a more intense stimulus and expressed greater skin conductance responses (SCR) to generalized stimuli of high intensity. Brain activity related to intensity-based fear generalization was observed in the striatum, insula, thalamus/periacqueductal gray, and subgenual cingulate cortex. The psychophysiological expression of generalized fear correlated with amygdala activity, and connectivity between the amygdala and extrastriate visual cortex was correlated with individual differences in trait anxiety. These findings reveal the brain regions and functional networks involved in flexibly responding to stimuli that resemble a learned threat. These regions may comprise an intensity-based fear generalization circuit that underlies retrospective biases in threat value estimation and overgeneralization of fear in anxiety disorders. (C) 2011 Elsevier Inc. All rights reserved.