The brain's representation of fear information is an adaptive mechanism that facilitates animals to avoid threats and gain a chance for survival. However, when the threat environment is transformed into a safe environment, the fear memory that is difficult to extinguish may affect the survival and quality of life of the animals. Intracranial electrophysiological researches in model animals suggest that the neural oscillations in the medial prefrontal cortex (mPFC)-amygdala pathway play a key role in the acquisition and extinction of fear memory. Theta activity of the amygdala and mPFC (eg, increased theta activity in the amygdala and mPFC after fear acquisition), and the interaction between them (eg, increased theta input from the mPFC to the amygdala after fear extinction) constitute the basic neural mechanism underpinning fear memory processing. The roles and neural activity characteristics of two functionally separated subregions of the human mPFC, the dorsal anterior cingulated (dACC) and the ventromedial prefrontal cortex (vmPFC) during fear memory processing in humans remain unclear. In addition, the directionality of information transmission in the human mPFC-amygdala pathway during fear acquisition and extinction need to be further explored. In this research, we investigated the characteristics and directionality of theta(4-8Hz) activity in the amygdala and mPFC during fear acquisition and extinction learning by using intracranial electroencephalography (EEG) with high temporal and spatial resolution, high signal-to-noise ratio and multi-site synchronous recording. Our results suggest that : (1) the enhanced theta activity of the amygdala can serve as a kind of stable neural representation of threat signals; (2) the enhancement of theta activity directionality from the vmPFC to the amygdala is a kind of stable connectivity representation of safety signals; (3) the implicit trial design rules during acquisition affect the subsequent CS+ representation of the current reinforced CS+ trial: compared with the first CS+ trial after the current enhanced CS+ trial, the theta activity of the amygdale in the second CS+ trial can be a more stable neural representation of the threat signals; (4) with the advancement of the extinction learning process, theta activity of the amygdala under CS+ becomes more and more like the theta activity representation of safety signal. This research made a preliminary exploration of the theta activity patterns of the amygdala and mPFC subregions and the directionality of information
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