Strengthened Hippocampal Circuits Underlie Enhanced Retrieval of Extinguished Fear Memories Following Mindfulness Training

Abstract

Background: The role of hippocampus in context-dependent recall of extinction is well recognized. However, little is known about how intervention-induced changes in hippocampal networks relate to improvements in extinction learning. In this study, we hypothesized that mindfulness training creates an optimal exposure condition by heightening attention and awareness of present moment sensory experience, leading to enhanced extinction learning, improved emotion regulation, and reduced anxiety symptoms.

Methods: We tested this hypothesis in a randomized controlled longitudinal study design using a 2-day fear conditioning and extinction protocol. The mindfulness training group included 42 participants (28 women) and the control group included 25 participants (15 women).

Results: We show that mindfulness training is associated with differential engagement of the right supramarginal gyrus as well as hippocampal-cortical reorganization. We also report enhanced hippocampal connectivity to the primary sensory cortex during retrieval of extinguished stimuli following mindfulness training.

Conclusions: These findings suggest hippocampal-dependent changes in contextual retrieval as one plausible neural mechanism through which mindfulness-based interventions enhance fear extinction and foster stress resilience.

Trial registration: ClinicalTrials.gov NCT01488422.

Keywords: Extinction; Extinction retrieval; Fear memory; Hippocampus; Mindfulness; fMRI.

Conflict of interest statement

Disclosures

All authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1 A.

Study design B. Fear Conditioning and Extinction Paradigm C. Changes in outcome measures. Error bars reflect standard deviations. Both interventions decreased perceived levels of stress, however MBSR was associated with further improvements in anxiety and emotion regulation levels.

Figure 2. A.

ROI analyses showing BOLD signal in hippocampus (left) during recall of extinguished stimuli for all participants at baseline. B. Regression plot showing a positive correlation between the extinction retention index and parameter estimates extracted from the hippocampus (using peak from Milad et al. 2007). B. Parameter estimates extracted from second-level one sample t-tests for each group and condition using the CS+E vs CS−contrasts. Error bars reflect standard errors.

Figure 3. A.

The results of group-by-time analysis mapped onto Conte69 atlas via Connectome Workbench using trilinear interpolation. B. Parameter estimates extracted from the peak [56, −40, 24], BA 40 using second-level one sample t-tests for each group and condition using the CS+E vs CS−contrasts. Compared to the control intervention, the MBSR intervention was associated with the higher engagement of a cluster in SMG/ posterior parietal cortex. C. Neural activity (parameter estimates of BOLD signal extracted from the peak following MBSR intervention) correlate with total amount of home meditation practice during the MBSR intervention. D. Changes in hippocampal functional connectivity during extinction recall following MBSR.

Figure 4.

Structural change in the hippocampus from pre to post predict increased functional connectivity between the hippocampus and dorsolateral prefrontal and retrosplenial cortices during the early phases recall at post for the MBSR group. The graphs show connectivity values between the hippocampus and (i) the dorsolateral prefrontal and (ii) retrosplenial cortices as they co-vary with symmetrized percent change in hippocampal signal intensity. X- axis depicts symmetrized percent change in hippocampal signal intensity, while Y-axis depicts the Fisher transformed correlation coefficient of connectivity between the hippocampus and the relevant cluster.