Changes in Resting-State Functional Connectivity Following Delay and Trace Fear Conditioning Acquisition and Extinction

Abstract

Consolidation is the process of stabilizing a recently acquired memory into a more permanent or durable form. Several studies with laboratory animals have uncovered valuable information about the process of consolidation, but less is known about the process of consolidation in healthy humans. The current study examined the consolidation of emotional memories in different brain circuits in healthy humans using resting-state fMRI. We used the acquisition and extinction of two variations of Pavlovian fear conditioning, delay and trace, which rely on slightly different circuits to examine changes in functional connectivity related to a general fear learning process and also to examine how these changes may differ in these circuits. We found that the acquisition of delay and trace fear conditioning involves similar circuitry including the amygdala, but that trace conditioning involves the addition of a few more brain regions to the general circuit including the hippocampus. Twenty-four hours following acquisition there was an increase in functional connectivity between the amygdala and several other brain areas including the hippocampus and medial prefrontal cortex for both the delay and trace groups suggesting that these changes reflect the consolidation of a general fear memory. We also observed changes in connectivity that were specific to the trace group in brain regions thought to be specifically involved in trace conditioning including the medial prefrontal cortex and the retrosplenial cortex. By seven days after acquisition most of the changes in connectivity had returned to baseline. Extinction data revealed that the ventromedial prefrontal cortex was involved in forming this inhibitory memory and that connectivity between the amygdala and a region of ventromedial prefrontal cortex increased for the trace group following extinction. These results suggest that consolidation can be measured in healthy humans using resting-state fMRI and that these processes occur in the same circuits that are responsible during training.