How cognitive and reactive fear circuits optimize escape decisions in humans

Abstract

Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost-benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking "virtual predators" constrain escape decisions. We show that rapid escape decisions rely on "reactive fear" circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with "cognitive fear" circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility. Using a Bayesian decision-making model, we further show that optimization of escape decisions under rapid flight were localized to the MCC, a region involved in adaptive motor control, while the hippocampus is implicated in optimizing decisions that update and control slower escape initiation. These results demonstrate an unexplored link between defensive survival circuits and their role in adaptive escape decisions.

Back to the Basics: Resting State Functional Connectivity of the Reticular Activation System in PTSD and its Dissociative Subtype

“…Deep-layer neuronal circuits that control innate and learned reflexive responses as well as arousal [99][100][101] are becoming increasingly important in the neurobiological conceptualization of PTSD. 1,2,[14][15][16]18,19,[65][66][67][99][100][101][102][103] Crucially, these fundamental neuronal circuits determine the general arousal state of the organism, laying the foundation for reflexive actions. 26 The present investigation provides novel evidence that as compared to both control subjects and individuals with PTSD, participants with PTSDþDS showed stronger rsFC of the PPN with the amygdala, the parahippocampal gyrus, the anterior cingulate cortex, and the ventromedial prefrontal cortex.…”

Dissociable neural systems for unconditioned acute and sustained fear

“…Our main finding was that acute threat elicited consistent activity in a distributed set of cortical, limbic, and cerebellar regions, most notably the prefrontal cortex, paracentral lobule, amygdala, cingulate cortex, insula, PAG, parrahippocampus, and thalamus. These regions have been previously identified as being active in response to threat (Mobbs et al, 2007;Qi et al, 2018;Zhu & Thagard, 2002). However, the activity of these regions was not associated with slower-frequency experience of fear, despite the high pass filter of 256s optimizing the GLM analysis to detect the low energy changes in fear ratings, which peaked at around 0.01Hz.…”

“…Instead, they work in concert throughout threat evaluation that gradually shifts from one to the other as threat increases in proximity. This insight would not have been possible using conventional model based approaches that require controlled stimuli discretely categorized into anticipatory and reactionary stimuli, and which would inevitably lead to the description of a binary system of pre and post threat onset (e.g., Mobbs et al, 2007;Qi et al, 2018). Instead, using naturalistic stimuli and a data driven approach that permits the reliability of neural activity to be established whilst accommodating the complex and dynamic nature of the neural signal and the realistic stimuli that elicits it Hasson et al, 2004), we were nevertheless able to not only confirm these systems, but reveal how they functionally interact during a fearful situation.…”

“…Several recent studies have shown that spatiotemporally distant threats elicit activity in the ventromedial prefrontal cortex, posterior cingulate cortex, hippocampus and amygdala, which are associated with a cognitive mechanism of fear that reflects the need for complex information processing and memory retrieval to generate an adaptive and flexible response. A threat that is proximal in space or time, on the other hand, elicits a reactive fear response of immediate action and fight or flight, and which elicits activity in the periaqueductal gray, amygdala, hypothalamus, and middle cingulate cortex (Mobbs et al, 2007;Qi, Hassabis, Sun, Guo, Daw, & Mobbs, 2018).…”

Distinct medial-temporal lobe mechanisms of encoding and amygdala-mediated memory reinstatement for disgust and fear

“…Likewise, it is known that disgust is a relatively complex, multifaceted emotion originating in distaste but extending to social domains and moral disgust, resulting in multisensory features specific to this emotion 76,77 . In contrast, fear may take different forms characterized as reactive or cognitive, and in case of slow escape decisions engage brain areas related to memory or threat anticipation, such as posterior cingulate cortex, HC, and ventromedial prefrontal cortex 78 . Moreover, both disgust and fear imply avoidance, but for different reasons 37 .…”