Abstract
Background
Overgeneralization of fear is a pathogenic marker of anxiety and stress-related disorders
and has been linked with perceptual discrimination deficits, reduced fear inhibition,
and prefrontal hyporeactivity to safety-signaling stimuli. We aimed to examine whether
behavioral and neural patterns of fear generalization are influenced by the fear-inhibiting
ventromedial prefrontal cortex (vmPFC).
Methods
Three groups of healthy participants received excitatory (n = 27), inhibitory (n = 26), or sham (n = 26) transcranial direct current stimulation of the vmPFC after a fear conditioning
phase and before a fear generalization phase. We obtained, as dependent variables,
fear ratings and unconditioned stimulus–expectancy ratings, perceptual aspects of
fear generalization (perceptual discrimination), pupil dilations, and source estimations
of event-related fields elicited by conditioned and generalization stimuli.
Results
After inhibitory (compared with excitatory and sham) vmPFC stimulation, we observed
reduced performance in perceptual discrimination and less negative inhibitory gradients
in frontal structures at midlatency and late time intervals. Fear and unconditioned
stimulus–expectancy ratings as well as pupil dilation remained unaffected by stimulation.
Conclusions
These findings reveal a causal contribution of vmPFC reactivity to generalization
patterns and suggest that vmPFC hyporeactivity consequent on inhibitory vmPFC stimulation
may serve as a model for pathological processes of fear generalization (reduced discrimination,
impaired fear inhibition via frontal brain structures). This encourages further basic
and clinical research on the potential of targeted brain stimulation to modulate fear
generalization and overgeneralization.
Keywords
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Article info
Publication history
Published online: August 14, 2021
Accepted:
August 2,
2021
Received in revised form:
July 15,
2021
Received:
May 10,
2021
Identification
Copyright
© 2021 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
