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Neural substrates of human fear generalization: A 7T-fMRI investigation. Neuroimage 2021 10 01;239:118308

Date

06/28/2021

Pubmed ID

34175426

DOI

10.1016/j.neuroimage.2021.118308

Scopus ID

2-s2.0-85109039158

Abstract

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 generalization, 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 stimuli 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 generalization 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.

Author List

Huggins AA, Weis CN, Parisi EA, Bennett KP, Miskovic V, Larson CL

Author

Carissa N. Weis PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptation, Psychological
Adolescent
Adult
Anxiety
Cerebral Cortex
Fear
Female
Functional Neuroimaging
Generalization, Stimulus
Habenula
Hippocampus
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Nerve Net
Septal Nuclei
Somatosensory Cortex
Thalamus
Uncertainty
Visual Cortex
Young Adult