Distributed and Multifaceted Effects of Threat and Safety

Abstract

In the present fMRI study, we examined how anxious apprehension is processed in the human brain. A central goal of the study was to test the prediction that a subset of brain regions would exhibit sustained response profiles during threat periods, including the anterior insula, a region implicated in anxiety disorders. A second important goal was to evaluate the responses in the amygdala and the bed nucleus of the stria terminals, regions that have been suggested to be involved in more transient and sustained threat, respectively. A total of 109 participants performed an experiment in which they encountered “threat” or “safe” trials lasting approximately 16 sec. During the former, they experienced zero to three highly unpleasant electrical stimulations, whereas in the latter, they experienced zero to three benign electrical stimulations (not perceived as unpleasant). The timing of the stimulation during trials was randomized, and as some trials contained no stimulation, stimulation delivery was uncertain. We contrasted responses during threat and safe trials that did not contain electrical stimulation, but only the potential that unpleasant (threat) or benign (safe) stimulation could occur. We employed Bayesian multilevel analysis to contrast responses to threat and safe trials in 85 brain regions implicated in threat processing. Our results revealed that the effect of anxious apprehension is distributed across the brain and that the temporal evolution of the responses is quite varied, including more transient and more sustained profiles, as well as signal increases and decreases with threat.

Acute nicotine abstinence amplifies subjective withdrawal symptoms and threat-evoked fear and anxiety, but not extended amygdala reactivity

“…While the Region × Threat Certainty interaction was only marginally significant (p=0.10), focal comparisons indicated that that the Ce showed an indiscriminate pattern of reactivity, with statistically indistinguishable levels of heightened activation during the anticipation of certain and uncertain threat. In contrast, the BST showed preferential activation during the anticipation of uncertain threat, consistent with a recent large-scale (n=109) study that employed anatomical ROIs (Murty et al, 2022). These observations are broadly consistent with the influential model of Davis and colleagues-which suggests that the Ce is involved in responding to both kinds of threat-but run counter to the popular double dissociation model (Ce: Certain >> Uncertain ≈ 0;…”

How many brain regions are needed to elucidate the neural bases of fear and anxiety?

“…In an influential model, the BST was proposed to be engaged by diffuse threat, whereas the central amygdala was proposed to be engaged by immediate threat (Davis and Whalen, 2001). This purported dissociation has been challenged by some researchers (Gungor and Pare, 2016;Shackman and Fox, 2016;Fox and Shackman, 2019), but the precise contributions of the BST and the central amygdala to sustained versus phasic processes, respectively, remains unresolved (for examples in humans, see Hur et al, 2020;Murty et al, 2022).…”

Brainstem networks construct threat probability and prediction error from neuronal building blocks

“…Our finding of widespread and organized brainstem threat signaling calls for the abandonment of the historical division of labor view. In its place, we must embrace a brain-wide view of threat computation 36 – 38 in which brainstem networks are not limited to organizing fear behavior but are integral to estimating threat.…”