Oscillatory correlates of threat imminence during virtual navigation.

The Predatory Imminence Continuum Theory proposes that defensive behaviors depend on the proximity of a threat. While the neural mechanisms underlying this proposal are well studied in animal models, it remains poorly understood in humans. To address this issue, we recorded EEG from 24 (15 female) young adults engaged in a first-person virtual reality Risk-Reward interaction task. On each trial, participants were placed in a virtual room and presented with either a threat or reward conditioned stimulus (CS) in the same room location (proximal) or different room location (distal). Behaviorally, all participants learned to avoid the threat-CS, with most using the optimal behavior to actively avoid the proximal threat-CS (88% accuracy) and passively avoid the distal threat-CS (69% accuracy). Similarly, participants learned to actively approach the distal reward-CS (82% accuracy) and to remain passive to the proximal reward-CS (72% accuracy). At an electrophysiological level, we observed a general increase in theta power (4-8 Hz) over the right posterior channel P8 across all conditions, with the proximal threat-CS evoking the largest theta response. By contrast, distal cues induced two bursts of gamma (30-60 Hz) power over midline-parietal channel Pz (200 msec post-cue) and right frontal channel Fp2 (300 msec post-cue). Interestingly, the first burst of gamma power was sensitive to the distal threat-CS and the second burst at channel Fp2 was sensitive to the distal reward-CS. Together, these findings demonstrate that oscillatory processes differentiate between the spatial proximity information during threat and reward encoding, likely optimizing the selection of the appropriate behavioral response.

Roles of the Amygdala and Basal Forebrain in Defense: a Reply to Luyck Et al. and Implications for Defensive Action.

The commentary by Luyck and colleagues on our paper provides many stimulating viewpoints and interpretations of our original study on dissociable responses in the amygdala and bed nucleus of the stria terminalis in threat processing. Here, we reply to some of the points raised and while agreeing with most of the comments also provide some alternative viewpoints. We end by putting forward a research agenda for how to further investigate the roles of these regions in threat processing, with an emphasis on studying their roles in defensive action.

The benefit of punishment sensitivity on motor performance under pressure.

OBJECTIVE: Humans are often required to perform demanding cognitive and motor tasks under pressure. However, in such environments there is considerable interindividual variability in the ability to successfully execute actions. Here, we consider how individual differences in self-reported sensitivity to punishment influence skilled motor performance under pressure and whether this relationship is moderated by the temporal detection of threat. METHOD: Across two studies, 160 UK participants (Study 1: N = 80, Mage = 21.6, 52 males; Study 2: N = 80, Mage = 24.95, 45 males) performed a precision-grip task and received either early or late warning of an upcoming stressful manipulation involving social evaluation and performance-dependent incentives. RESULTS: In both studies, we report an interaction where punishment sensitivity was adaptive for motor performance only when threats were detected early and there was opportunity to prepare for the upcoming stressor. Further, our results suggest that the benefits of punishment sensitivity are likely underpinned by the effective use of cognitive strategies. CONCLUSION: Heightened sensitivity to punishment is adaptive for performance under pressure, provided threats are detected early and effective cognitive strategies are implemented.

The convergence between defence and care in mammals.

The motivations to protect oneself and others have often been seen as conflicting. Here, we discuss recent evidence that self-defensive mechanisms may in fact be recruited to enable the helping of others. In some instances, the defensive response to a threat may even be more decisive in promoting helping than the response to a conspecific's distress (as predicted by empathy-altruism models). In light of this evidence, we propose that neural mechanisms implicated in self-defence may have been repurposed through evolution to enable the protection of others, and that defence and care may be convergent rather than conflicting functions. Finally, we present and discuss a working model of the shared brain mechanisms implicated in defence of both self and others.

Understanding anxiety symptoms as aberrant defensive responding along the threat imminence continuum.

Threat-anticipatory defensive responses have evolved to promote survival in a dynamic world. While inherently adaptive, aberrant expression of defensive responses to potential threat could manifest as pathological anxiety, which is prevalent, impairing, and associated with adverse outcomes. Extensive translational neuroscience research indicates that normative defensive responses are organized by threat imminence, such that distinct response patterns are observed in each phase of threat encounter and orchestrated by partially conserved neural circuitry. Anxiety symptoms, such as excessive and pervasive worry, physiological arousal, and avoidance behavior, may reflect aberrant expression of otherwise normative defensive responses, and therefore follow the same imminence-based organization. Here, empirical evidence linking aberrant expression of specific, imminence-dependent defensive responding to distinct anxiety symptoms is reviewed, and plausible contributing neural circuitry is highlighted. Drawing from translational and clinical research, the proposed framework informs our understanding of pathological anxiety by grounding anxiety symptoms in conserved psychobiological mechanisms. Potential implications for research and treatment are discussed.

Adaptation of Threat Responses Within the Negative Valence Framework.

External threats are a major source of our experience of negatively valanced emotion. As a threat becomes closer and more real, our specific behavior patterns and our experiences of negative affect change in response to the perceived imminence of threat. Recognizing this, the National Institute of Mental Health's Research Domain Criteria (RDoC) Negative Valence system is largely based around different levels of threat imminence. This perspective describes the correspondence between the RDoC Negative Valence System and a particular neurobiological/neuroecological model of reactions to threat, the Predatory Imminence Continuum (PIC) Theory. Using the COVID-19 pandemic as an illustration, we describe both adaptive and maladaptive behavior patterns from this perspective to illustrate how behavior in response to a crisis may get shaped. We end with suggestions on how further consideration of the PIC suggests potential modifications of the negative valence systems RDoC.

Negative valence systems: sustained threat and the predatory imminence continuum.

This review describes the relationship between the National Institute of Mental Health (U.S.A.) Research Domain Criteria (RDoC) Negative Valence System related to responses to threat and the Predatory Imminence Continuum model of antipredator defensive behavior. While the original RDoC constructs of Potential Threat (anxiety) and Acute Threat (fear) fit well with the pre-encounter and post-encounter defense modes of the predatory imminence model, the Sustained Threat construct does not. Early research on the bed nuclei of the stria terminalis (BST) suggested that when fear responding needed to be sustained for a prolonged duration this region was important. However, follow-up studies indicated that the BST becomes critical not because responses needed to be sustained but rather when the stimuli triggering fear were more difficult to learn about, particularly when aversive stimuli were difficult to accurately predict. Instead, it is argued that the BST and the hippocampus act to expand the range of conditions that can trigger post-encounter defense (Acute Threat). It is further suggested that sustained threat refers to situations where the predatory imminence continuum becomes distorted causing defensive behavior to intrude into times when organisms should be engaging in other adaptive behaviors. Stress is seen as something that can cause a long-term disturbance of the continuum and this disturbance is a state of sustained threat.

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.

Space, Time, and Fear: Survival Computations along Defensive Circuits.

Naturalistic observations show that decisions to avoid or escape predators occur at different spatiotemporal scales and that they are supported by different computations and neural circuits. At their extremes, proximal threats are addressed by a limited repertoire of reflexive and myopic actions, reflecting reduced decision and state spaces and model-free (MF) architectures. Conversely, distal threats allow increased information processing supported by model-based (MB) operations, including affective prospection, replay, and planning. However, MF and MB computations are often intertwined, and under conditions of safety the foundations for future effective reactive execution can be laid through MB instruction of MF control. Together, these computations are associated with distinct population codes embedded within a distributed defensive circuitry whose goal is to determine and realize the best policy.

Dynamics of Defensive Response Mobilization to Approaching External Versus Interoceptive Threat.

BACKGROUND: Excessive fear and anxiety are core features of anxiety disorders. Defensive response mobilization varies dynamically with threat proximity. METHODS: We analyzed defensive responses in 48 healthy students to an approaching external, predator-like threat (an electric shock resembling a predator attack) versus an approaching threat from inside the body (feeling of dyspnea as evoked by forced breath-holding). Threats either were inevitable or could be avoided by button press. RESULTS: Autonomic changes (heart rate, skin conductance), defensive reflex priming (startle eyeblink response), respiratory responses, and event-related potentials were assessed. Regardless of its source, when an approaching threat was inevitable, a defensive pattern emerged characterized by an increase in skin conductance, a potentiation of the startle reflex, and bradycardia. Minute ventilation increased only with approaching dyspnea. In preparation for active avoidance of either threat, startle magnitudes were inhibited and probe-elicited P3 wave amplitudes were reduced. Moreover, generation of avoidant action resulted in heart rate acceleration. CONCLUSIONS: This study demonstrates common and specific defensive activation patterns for approaching external and respiratory threats. The specific modulation in respiration in response to an inevitable respiratory threat may have important implications for our understanding of the etiology of anxiety disorders, especially panic disorder.

The Role of Learning in Threat Imminence and Defensive Behaviors.

Life threatening situations as urgent as defending against a predator precludes the use of slow trial and error strategies. Natural selection has led to the evolution of a behavioral system that has 3 critical elements. 1) When it is activated it limits the behaviors available to the organism to a set of prewired responses that have proven over phylogeny to be effective at defense. 2) A rapid learning system, called Pavlovian fear conditioning, that has the ability to immediately identify threats and promote prewired defensive behaviors. 3) That learning system has the ability to integrate several informational dimensions to determine threat imminence and this allows the organism to match the most effective defensive behavior to the current situation. The adaptive significance of conscious experiential states is also considered.

Reconciling RDoC and DSM approaches in clinical psychophysiology and neuroscience.

The Research Domain Criteria (RDoC) initiative endeavors to foster a science of psychopathology based around dimensions of brain-behavior relationships as opposed to subjectively based diagnostic categories. A rapidly accumulating array of transdiagnostic commonalities, across multiple objective and subjective measures, underscores the clear potential of this initiative. At the same time, a road map for guiding future RDoC research efforts is needed that draws upon the wealth of extant disorder-specific findings. In this issue, Hamm and colleagues provide an example of conceptualizing within-disorder processes in terms of dimensional brain-behavior relationships that advances the understanding of panic disorder with agoraphobia beyond the conventional nosological framework. Their findings and conceptual model are reviewed and discussed in terms of broader transdiagnostic implications.