Neural substrates of human fear generalization: A 7T-fMRI investigation

Fear generalization -the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of gener-alization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stim-uli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater gen-eralization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.

Automated summary

Fear generalization is an adaptive process that helps individuals interpret ambiguous stimuli as threatening, but overgeneralization can lead to maladaptive outcomes associated with anxiety disorders. Neuroimaging research has identified brain regions sensitive to generalization effects, with potential contributions from small brain regions like the hippocampal subfields and habenula. The study used high spatial resolution imaging to explore neural circuits involved in threat discrimination and generalization, revealing associations between brain activation patterns and individual differences in anxiety.