The neurocomputational link between defensive cardiac states and approach-avoidance arbitration under threat.

Avoidance, a hallmark of anxiety-related psychopathology, often comes at a cost; avoiding threat may forgo the possibility of a reward. Theories predict that optimal approach-avoidance arbitration depends on threat-induced psychophysiological states, like freezing-related bradycardia. Here we used model-based fMRI analyses to investigate whether and how bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration under varying reward and threat magnitudes. We show that bradycardia states are associated with increased threat-induced avoidance and more pronounced reward-threat value comparison (i.e., a stronger tendency to approach vs. avoid when expected reward outweighs threat). An amygdala-striatal-prefrontal circuit supports approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating reward-threat value and bradycardia states. These findings highlight the role of human freezing states in value-based decision making, relevant for optimal threat coping. They point to a specific role for amygdala/dACC in state-value integration under threat.

Tackling Costly Fearful Avoidance Using Pavlovian Counterconditioning.

Avoidance behavior constitutes a major transdiagnostic symptom that exacerbates anxiety. It hampers fear extinction and predicts poor therapy-outcome. Pavlovian counterconditioning with a reward could alleviate avoidance better than traditional extinction by reducing negative valence of the feared situation. However, previous studies are scarce and did not consider that pathological avoidance is often costly and typically evolves from an approach-avoidance conflict. Therefore, we used an approach-avoidance conflict paradigm to model effects of counterconditioning on costly avoidance (i.e., avoidance that leads to missing out on rewards). Results from our preregistered Bayesian Mixed Model analyses in 51 healthy participants (43 females) indicated that counterconditioning was more effective in reducing negative valuation and decreasing costly avoidance than traditional extinction. This study supports application of a simple counterconditioning technique, shows that its efficacy transfers to more complex avoidance situations, and suggests treatment may benefit from increasing reward drive in combination with extinction to overcome avoidance. Application in a clinical sample is a necessary next step to assess clinical utility of counterconditioning.

Correction: Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.

[This corrects the article DOI: 10.1371/journal.pone.0260952.].

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.

Roles of the bed nucleus of the stria terminalis and amygdala in fear reactions.

The bed nucleus of the stria terminalis (BNST) plays a critical modulatory role in driving fear responses. Part of the so-called extended amygdala, this region shares many functions and connections with the substantially more investigated amygdala proper. In this chapter, we review contributions of the BNST and amygdala to subjective, behavioral, and physiological aspects of fear. Despite the fact that both regions are together involved in each of these aspects of fear, they appear complimentary in their contributions. Specifically, the basolateral amygdala (BLA), through its connections to sensory and orbitofrontal regions, is ideally poised for fast learning and controlling fear reactions in a variety of situations. The central amygdala (CeA) relies on BLA input and is particularly important for adjusting physiological and behavioral responses under acute threat. In contrast, the BNST may profit from more extensive striatal and dorsomedial prefrontal connections to drive anticipatory responses under more ambiguous conditions that allow more time for planning. Thus current evidence suggests that the BNST is ideally suited to play a critical role responding to distant or ambiguous threats and could thereby facilitate goal-directed defensive action.

Approach-Avoidance Decisions Under Threat: The Role of Autonomic Psychophysiological States.

Acutely challenging or threatening situations frequently require approach-avoidance decisions. Acute threat triggers fast autonomic changes that prepare the body to freeze, fight or flee. However, such autonomic changes may also influence subsequent instrumental approach-avoidance decisions. Since defensive bodily states are often not considered in value-based decision-making models, it remains unclear how they influence the decision-making process. Here, we aim to bridge this gap by discussing the existing literature on the potential role of threat-induced bodily states on decision making and provide a new neurocomputational framework explaining how these effects can facilitate or bias approach-avoid decisions under threat. Theoretical accounts have stated that threat-induced parasympathetic activity is involved in information gathering and decision making. Parasympathetic dominance over sympathetic activity is particularly seen during threat-anticipatory freezing, an evolutionarily conserved response to threat demonstrated across species and characterized by immobility and bradycardia. Although this state of freezing has been linked to altered information processing and action preparation, a full theoretical treatment of the interactions with value-based decision making has not yet been achieved. Our neural framework, which we term the Threat State/Value Integration (TSI) Model, will illustrate how threat-induced bodily states may impact valuation of competing incentives at three stages of the decision-making process, namely at threat evaluation, integration of rewards and threats, and action initiation. Additionally, because altered parasympathetic activity and decision biases have been shown in anxious populations, we will end with discussing how biases in this system can lead to characteristic patterns of avoidance seen in anxiety-related disorders, motivating future pre-clinical and clinical research.

Individual differences in costly fearful avoidance and the relation to psychophysiology.

Excessive avoidance behaviour is a cardinal symptom of anxiety disorders. Avoidance is not only associated with the benefits of avoiding threats, but also with the costs of missing out on rewards upon exploration. Psychological and psychophysiological mechanisms contributing to these costly avoidance decisions in prospect of mixed outcomes remain unclear. We developed a novel Fearful Avoidance Task (FAT) that resembles characteristics of real-life approach-avoidance conflicts, enabling to disentangle reward and threat effects. Using the FAT, we investigated individual differences in avoidance behaviour and anticipatory psychophysiological states (i.e. startle reflex and skin conductance) in a relatively large sample of 343 (78 females) participants. Avoidance under acute threat of shock depends on a trade-off between perceived reward and threat. Both increased startle and skin conductance in the absence of threat of shock emerged as predictors of increased avoidance (potentially indicative of fear generalization). Increased avoidance was also associated with female sex and trait anxiety, dependent on reward and threat levels. Our findings highlight distinct possible predictors of heightened avoidance and add to mechanistic understanding of how individual propensity for costly avoidance may emerge. Distinct avoidance typologies based on differential reward and threat sensitivities may have different mechanistic origins and thereby could benefit from different treatment strategies.