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Updated: May 24, 2026

Investigating the Neural Mechanisms of Aware and Unaware Fear Memory with fMRI
Published on: October 6, 2011
Brain activation during fear conditioning in humans depends on genetic variations related to functioning of the
S Ridder1, J Treutlein2, F Nees1
1Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Background:
Enhanced acquisition and delayed extinction of fear conditioning are viewed as major determinants of anxiety disorders, which are often characterized by a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis.
Method:
In this study we employed cued fear conditioning in two independent samples of healthy subjects (sample 1: n=60, sample 2: n=52). Two graphical shapes served as conditioned stimuli and painful electrical stimulation as the unconditioned stimulus. In addition, guided by findings from published animal studies on HPA axis-related genes in fear conditioning, we examined variants of the glucocorticoid receptor and corticotropin-releasing hormone receptor 1 genes.
Results:
Variation in these genes showed enhanced amygdala activation during the acquisition and reduced prefrontal activation during the extinction of fear as well as altered amygdala-prefrontal connectivity.
Conclusions:
This is the first demonstration of the involvement of genes related to the HPA axis in human fear conditioning.
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