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

Abstract

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.

Variance and Scale-Free Properties of Resting-State Blood Oxygenation Level-Dependent Signal After Fear Memory Acquisition and Extinction

“…Simultaneously, we hypothesized that the variance should increase during the task as an indirect index of neural efficiency (Labrenz et al, 2019). We also expected to find residual changes of both LRTC and variance in areas of fear-processing brain network in the post-task resting state, as it was early reported for functional connectivity of the BOLD signal (Schultz et al, 2012;Feng et al, 2015;Martynova et al, 2020). Understanding the variability and fractal properties of brain dynamics may enhance knowledge regarding the spatiotemporal structure of spontaneous brain activity, its modulation after emotional stimulation, and its potential as a biomarker of affective disorders.…”

“…During the resting-state scanning, participants were asked to remain calm with eyes closed and to try not to think purposefully. A full description of the experimental procedure can be found in our previous article (Martynova et al, 2020). In the current study, we concentrated on analyzing three sessions on the first day of scanning to capture the immediate changes in the LRTC.…”

“…In addition, the fear extinction network (FEN) from a metaanalysis (Fullana et al, 2018) and the task-related contrast (TRC) from our previous fear extinction study (Martynova et al, 2020) were used as regions of interest (ROIs). We took only 17 ROIs from the FEN (see Supplementary Table 1), which overlapped with those from the BN Atlas but were not located in the brainstem or the cerebellum.…”

“…However, little is known about how fear-inducing conditions may influence the variance and fractality of brain activity during the task and subsequent resting state. Previous studies reported that stress and fear could induce temporal changes in the resting-state functional connectivity (Schultz et al, 2012;Feng et al, 2015;Martynova et al, 2020). Abnormal resting-state connectivity was also repeatedly shown in fear-conditioning studies in patients who had post-traumatic stress disorders (PTSD) (Rauch et al, 2006;Rabinak et al, 2011) and anxiety (for review, Northoff, 2020).…”

“…Based on our previous findings on persistent changes of functional connectivity in resting state after fear learning and fear memory extinction (Tetereva et al, 2020;Martynova et al, 2020), we assumed that if a regional and network correlation of the brain activity can change after stimulation, it should consequently be reflected in the variance and scale-free properties of the BOLD signal. To test this hypothesis, we tested changes that occurred in the LRTC of resting-state BOLD signals after fear learning and fear memory extinction in comparison to the initial pre-task resting state.…”