The Neural Mechanism Of Fear Memory Consolidation And Reconsolidation

Fear is closely related to the evolution of the basic emotions, it is biologically adaptive responses to environmental threat. Classical fear conditioning is regarded as a model paradigm to study the neural systems of fear. Using this paradigm, researchers have been able to map the pathways of the neural mechanisms of fear learning and extinction. Extensive neurophysiological and brain imaging research have established several key regions involved in fear learning and expression processes, including the amygdala, insula, dorsal anterior cingulate (dACC), prefrontal cortex and temporal cortex. The neural circuit involved in fear extinction processes included the amygdala, hippocampus (Hip), ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulated cortex (dACC). From fear acquisition to extinction, there are another two steps of fear process:consolidation and reconsolidation. As the fear memory consolidation and reconsolidation was automatic and the methodology was not fully developed yet, little is known about brain regions and functional networks of automatic memory consolidation and reconsolidation of fear conditioning when the brain is "at rest" following fear acquisition. However, a wealth of behavioral research suggested that the window of automatic memory consolidation and reconsolidation as well as experimental manipulation (mainly "reactivation" or "no reactivation") were play crucial role in fear extinction. Resting-state functional magnetic resonance imaging (rs-fMRI) was regarded as important tools to examine spontaneous brain activity and the integrity of interregional functional coupling. Therefore, using rs-fMRI, from the plastic perspective, the present study attempted to examine neural substrates and functional networks of automatic memory consolidation, reconsolidation and extinction (long-term extinction temporarily extinction) of fear conditioning. The present research mainly focus on two the problems:(1) The neural mechanism of automatic memory consolidation;(2) The ready state of the brain and the fear extinction (long-term extinction temporarily extinction) effected by reactivation or no reactivation during fear memory reconsolidation.In research Ⅰ, using rs-fMRI, the present study attempted to examine neural substrates and functional networks of automatic memory consolidation of fear conditioning. The experiment began with a baseline rest condition (REST1,10min), then participants completed fear acquisition task (40min) before the experimental rest condition (REST2,10min). Our study yielded four main findings. First, in line with prior researches, several key regions (amygdala, dACC, mPFC, insula, thalamus and temporal lobe) which labeled as the neural biomarkers of fear acquisition were emerged in our task design. Second, the neural circuit involved in automatic memory consolidation of fear conditioning processes included the amygdala, dACC and mPFC; Third, functional connectivity analysis showed that amygdala-dACC and hippocampus-insula functional connectivity was enhanced, whereas the amygdala-mPFC coupling was decreased during fear memory consolidation. Finally, the change in amygdala-mPFC functional connectivity (REST2versus REST1) could predict the subjective fear. Besides, increased vmPFC-insula coupling was positively correlated with the level of trait anxiety. Therefore, the amygdala, dACC, mPFC serves a key role in the automatic consolidation of fear memory, and the changes of functional connectivity not only indicated the plasticity of fear neural network, but also reflects the effect of the fear memory consolidation.In research Ⅱ, the participants in the experimental group (the first day) were divided into two groups. In one of groups (n=20) the fear memory was reactivated before extinction. The other (n=20) was not reminded of the fear memory before extinction training. We investigated the ready state of the brain and the fear extinction (long-term extinction temporarily extinction) effected by reactivation or no reactivation during fear memory reconsolidation. Our study yielded four main findings. Firstly, some brain areas showed greater activation in the reminder group than in no reminder group, including vmPFC and dACC. Second, functional connectivity analysis revealed that the reminder group was greater functional connectivity between vmPFC and amygdala comparing with the no reminder group. Thirdly, there was no significant difference in brain activity between the two groups during the stage of fear memory extinction (the second day). Finally, significantly greater activity was evident bilaterally in the basolateral amygdala in the reminder group as compared with the non-reminder group during the stage of fear memory re-extinction (the third day). Therefore, extinction conducted during the reconsolidation window of an old fear memory prevented the spontaneous recovery or the reinstatement of fear responses. Moreover, this manipulation selectively affected only the reactivated conditioned stimulus while leaving fear memory to the other non-reactivated conditioned stimulus intact. However, the ready state of the brain (the activation of the vmPFC) was play key role in the extinction. Moreover, the vmPFC mediates the activation of other brain regions, including amygdala and dACC.Combined, the present study revealed that:(1) amygdala, dACC and mPFC serve crucial role in automatic memory consolidation of fear conditioning;(2) the changes of functional connectivity not only indicated the plasticity of fear neural network, but also reflects the effect of the fear memory consolidation;(3) the ready state of the brain (the activation of the vmPFC) was play key role in the extinction. Moreover, the vmPFC mediates the activation of other brain regions, including amygdala and dACC;(4) following the reminder of the fear memory, the extinction can prevent the return of the fear, the effect may last a long time, but in respected to the extinction without the reminder of the fear memory, the fear memory may spontaneously recover. From the plastic perspective, we investigated the neural mechanism of the consolidation, the reconsolidation and the extinction. Accordingly, the present study provides a new perspective for understanding fear memory consolidation and reconsolidation. It also may represent a first step towards understanding the early phase of psychological trauma etiology.