Fear bradycardia and activation of the human periaqueductal grey

Animal models of predator defense distinguish qualitatively different behavioral modes that are activated at increasing levels of predation threat. A defense mode observed at intermediate threat levels is freezing: a cessation of locomotion that is characterized by a parasympathetically dominated autonomic nervous system response that causes heart rate deceleration, or fear bradycardia. Studies in rodents have shown that freezing depends on amygdalar projections to the periaqueductal grey (PAG). In humans, freezing-like behaviors are implicated in development and maintenance of psychopathology, but neural mechanisms underlying freezing or its characteristic autonomic response profile have not been identified. Here, we combined event-related blood oxygenation level-dependent functional MRI (BOLD-fMRI) with autonomic response measures in a picture viewing paradigm to probe activity and interconnectivity within the amygdala-PAG pathway and test for an association with parasympathetic as opposed to sympathetic activation. In response to negatively arousing pictures, we observed parasympathetic (bradycardia) and sympathetic (pupil dilation) autonomic responses, BOLD responses in the amygdala and PAG, and effective connectivity between these regions. Critically, BOLD responses in the PAG to negative pictures correlated on a trial-by-trial basis with bradycardia but not pupil dilation. This correlation with bradycardia remained significant when partialling out pupil dilation. Additionally, activity in regions associated with motor planning and inhibition mirrored the PAG response. Thus, our findings implicate the human PAG in a parasympathetically dominated defense mode that subserves a state of attentive immobility. Mechanistic insight into this qualitatively distinct defense mode may importantly advance translational models of anxiety disorders.