Network model of fear extinction and renewal functional pathways

Abstract

The objective of this study was to examine the opposite behavior responses of conditioned fear extinction and renewal and how they are represented by network interactions between brain regions. This work is a continuation of a series of brain mapping studies of various inhibitory phenomena, including conditioned inhibition, blocking and extinction. A tone–footshock fear conditioning paradigm in rats was used, followed by extinction and testing in two different contexts. Fluorodeoxyglucose autoradiography was used to compare mean regional brain activity and interregional correlations resulting from the presentation of the extinguished tone in or out of the extinction context. A confirmatory structural equation model, constructed from a neural network proposed to underlie fear extinction, showed a reversal from negative regional interactions during extinction recall to positive interactions during fear renewal. Additionally, the magnitude of direct effects was different between groups, reflecting a change in the strength of the influences conveyed through those pathways. The results suggest that the extinguished tone encountered outside of the extinction context recruits auditory and limbic areas, which in turn influence the interactions of the infralimbic cortex with the amygdala and ventrolateral periaqueductal gray. Interestingly, the results also suggest that two independent pathways influence conditioned freezing: one from the central amygdaloid nucleus and the other from the infralimbic cortex directly to the ventrolateral periaqueductal gray.