Longitudinal changes of resting-state functional connectivity of amygdala following fear learning and extinction

Altered functional connectivity of the amygdala has been observed in a resting state immediately after fear learning, even one day after aversive exposure. The persistence of increased resting-state functional connectivity (rsFC) of the amygdala has been a critical finding in patients with stress and anxiety disorders. However, longitudinal changes in amygdala rsFC have rarely been explored in healthy participants. To address this issue, we studied the rsFC of the amygdala in two groups of healthy volunteers. The control group participated in three fMRI scanning sessions of their resting state at the first visit, one day, and one week later. The experimental group participated in three fMRI sessions on the first day: a resting state before fear conditioning, a fear extinction session, and a resting state immediately after fear extinction. Furthermore, this group experienced scanning after one day and week. The fear-conditioning paradigm consisted of visual stimuli with a distinct rate of partial reinforcement by electric shock. During the extinction, we presented the same stimuli in another sequence without aversive pairing. In the control group, rsFC maps were statistically similar between sessions for the left and right amygdala. However, in the experimental group, the increased rsFC mainly of the left amygdala was observed after extinction, one day, and one week. The between-group comparison also demonstrated an increase in the left amygdala rsFC in the experimental group. Our results indicate that functional connections of the left amygdala influenced by fear learning may persist for several hours and days in the human brain.