Computational modeling of threat learning reveals links with anxiety and neuroanatomy in humans

Abstract

Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. We recorded skin-conductance data during a threat-learning task from individuals with and without anxiety disorders (N=251; 8-50 years; 116 females). Reinforcement-learning model variants quantified processes hypothesized to relate to anxiety: threat conditioning, threat generalization, safety learning, and threat extinction. We identified the best-fitting models for these processes and tested associations among latent learning parameters, whole-brain anatomy, and anxiety severity. Results indicate that greater anxiety severity related specifically to slower safety learning and slower extinction of response to safe stimuli. Nucleus accumbens gray-matter volume moderated learning-anxiety associations. Using a modeling approach, we identify computational mechanisms linking threat learning and anxiety severity and their neuroanatomical substrates.

Anxiety as a disorder of uncertainty: implications for understanding maladaptive anxiety, anxious avoidance, and exposure therapy

“…One explanation may be that fear-related symptoms and disorders are more related to these learning differences than distress-related disorders (Clark & Watson, 1991;McTeague & Lang, 2012b). Other learning differences in the studies reviewed in Table 2 indicate differences in learning from good versus bad outcomes, but this learning impairment also appears in studies of depression (Abend et al, 2022;Brown et al, 2021;Gagne et al, 2020;Lamba et al, 2020;Wise & Dolan, 2020). The direction of results in individual studies varies; a recent computational meta-analysis suggested that anxiety and depression show greater punishment learning rates (Pike & Robinson, 2022).…”

Broadening the scope: Multiple functional connectivity networks underlying threat and safety signaling

“…However, learning to accurately respond to a threat requires multiple learning episodes to appropriately understand threat contingencies. Deficits in appropriate threat identification or threat response can lead to behavioral outcomes resembling an anxiety disorder (Abend et al, 2022;Britton et al, 2011;Robinson et al, 2013). Consequently, fearand anxiety-related disorders are often thought to be characterized by aberrations in threat processing and conditioning (Craske et al, 2017;Fenster et al, 2018).…”

An ancient subcortical circuit decides when to orient to threat in humans

“…Until recently 1 , the understanding of cognitive and neural mechanisms related to fear and anxiety has depended on experimental paradigms in which the impact of fear-inducing stimuli on behavior and neural activity can be investigated in the laboratory. Despite their elegance and continuing and critical importance 2 , such paradigms do not capture an important feature of fear-related behavior in the everyday lives of humans and other animals: the balancing of attention between threat and reward. In everyday life people must attend vigilantly to stimuli that presage adverse events but also to the stimuli predictive of positive events.…”