Memory consolidation of fear conditioning: bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex

Abstract

Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of memory consolidation of fear conditioning is not well understood. To address this question, we measured brain activity and the changes in functional connectivity following fear acquisition using resting-state functional magnetic resonance imaging. The amygdala-dorsal anterior cingulate cortex (dACC) and hippocampus-insula functional connectivity were enhanced, whereas the amygdala-medial prefrontal cortex (mPFC) functional coupling was decreased during fear memory consolidation. Furthermore, the amygdala-mPFC functional connectivity was negatively correlated with the subjective fear ratings. These findings suggest the amygdala functional connectivity with dACC and mPFC may play an important role in memory consolidation of fear conditioning. The change of amygdala-mPFC functional connectivity could predict the subjective fear. Accordingly, this study provides a new perspective for understanding fear memory consolidation.

Keywords: amygdala; fear memory consolidation; functional connectivity; resting-state fMRI.

Fig. 1

Schematic illustration of the paradigm for the fMRI experiment

Fig. 2

Areas of brain activation in fear acquisition for the CS+ vs CS− condition. Based on functional result, we extract the ROI for resting analysis. The individual peak voxel within the group ROI was used for T-value and time course extraction for each subject.

Fig. 3

Inter-regional functional coupling change over time. Sagittal views of inter-regional functional coupling maps, focused on the amygdala coupling with dACC and the mPFC separately obtained from before fear acquisition (left) and after fear acquisition (right) (P = 0.01, Bonferroni corrected).

Fig. 4

The change in amygdala–dACC, amygdala–mPFC and Hippocampus–insula, functional coupling change over time between REST1 and REST2; asterisk indicates P < 0.05.

Fig. 5

Individual difference in the change (Δcorrelation coefficient) of amgydala–mPFC functional connectivity predicted individuals’ subjective fear ratings, r = −0.43, P = 0.03

Fig. 6

High-trait anxiety was associated with enhanced functional connectivity between vmPFC and insula during fear memory consolidation, r = 0.46, P = 0.02.