Abstract:

Fear is a biologically adaptive response to environmental threats, and fear learning plays a key role in adaptive function. However, maladaptive fear learning underlies emotional disorders, such as anxiety and posttraumatic stress disorder (PTSD). Together with the development of cognitive neuroscience and the integration of multidisciplinary research, the study on the cognitive neural mechanism of fear has become a hot topic in the field of emotion. Using the classical fear conditioning paradigm, researchers have identified the brain circuits of fear learning and extinction. Specifically, extensive imaging researches have revealed several key regions involved in fear acquisition, including the amygdala, insula, dorsal anterior cingulate (dACC) and thalamus. Moreover, the amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC) served key roles in fear memory consolidation and reconsolidation, and the amygdala, hippocampus, vmPFC, and dACC are required for fear extinction. Cumulative evidence has suggested that oxytocin plays a crucial role in the process of fear acquisition, fear consolidation and fear extinction. Therefore, firstly, we summarized the paradigms of fear acquisition and fear extinction as well as the cognitive neural mechanisms of fear acquisition and fear extinction based on the fingdings of corresponding meta-analyses. Secondly, we focused on the cognitive neural mechanisms underlying the impact of oxytocin on fear acquisition and fear extinction. Next, we summarized the neurobiological circuits of oxytocin influence on fear emotion processing. Finally, we prospected the future researches on the cognitive neural mechanisms underlying the impact of oxytocin on fear processing. The present study sheds insights into the cognitive neural mechanisms underlying the impact of oxytocin on fear processing. Moreover, the present study provides an potential treatment for the fear-related disorders.

Oxytocin has been shown to facilitate fear acquisition as it affects brain activity in several regions including amygdala, prefrontal cortex, anterior cingulate gyrus, insula and hippocampus, as well as the functional connectivity between them. Oxytocin also enhances fear extinction by regulating amygdala and medial prefrontal cortex activity, as well as enhancing the functional connectivity between prefrontal cortex and amygdala. Furthermore, oxytocin can regulate the activity of the amygdala, anterior cingulate gyrus, insula, hippocampus, vmPFC and other fear-related brain regions, thus affecting the processes of fear acquisition and extinction. Specifically, cumulative evidence has indicated that intranasal oxytocin attenuates amygdala (hyper)activity and enhances functional coupling of the amygdala with the vmPFC and hippocampus, resulting in increased top-down control over the fear response. In addition, intranasal oxytocin has also been found to attenuate amygdala—brainstem connectivity and to change activity and connectivity in nodes of the salience network (i.e., insula and dACC). Furthermore, oxytocin administration may enhance social behavior through modulating the hypothalamus—pituitary—adrenal (HPA) axis and autonomic nervous system (ANS) function, which may provide a potential treatment for the fear-related disorders. However, it should be noted that the dose, time and location of oxytocin injection might have different effects on the processes of fear acquisition and extinction.

Future studies should focus on gender differences, neural network underlying the impact of oxytocin on fear consolidation and reconsolidation and the pathological study examining oxytocin effect on fear emotion processing to better reveal the cognitive neural mechanisms underlying the impact of oxytocin on.

Key words: oxytocin, fear acquisition, fear extinction, amygdala, vmPFC