Threat Vigilance and Intrinsic Amygdala Connectivity

A well documented amygdala-dorsomedial prefrontal circuit is theorized to promote attention to threat (‘threat vigilance’). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g. through threat-of-shock and movie-watching). In the present study, we predicted that—for those scoring high in self-reported anxiety and a behavioral measure of threat vigilance—this circuitry is chronically engaged, even in the absence of anxiogenic stimuli. Our analyses of resting-state fMRI data (N=639) did not, however, provide evidence for such a relationship. Nevertheless, in our planned exploratory analyses, we saw a relationship between threat vigilance behavior (but not self-reported anxiety) and intrinsic amygdala-periaqueductal gray connectivity. Here, we suggest this subcortical circuitry may be chronically engaged in hypervigilant individuals, but that the amygdala-prefrontal circuitry may only be engaged in response to anxiogenic stimuli.

Anxiety attenuates learning advantages conferred by statistical stability and induces loss of volatility-attuning in brain activity

Anxiety can alter an individual's perception of their external sensory environment. Previous studies suggest that anxiety can increase the magnitude of neural responses to unexpected (or surprising) stimuli. Additionally, surprise responses are reported to be boosted during stable compared to volatile environments. Few studies, however, have examined how learning is impacted by both threat and volatility. To investigate these effects, we used threat-of-shock to transiently increase subjective anxiety in healthy adults during an auditory oddball task, in which the regularity could be stable or volatile, while undergoing functional Magnetic Resonance Imaging (fMRI) scanning. We then used Bayesian Model Selection (BMS) mapping to pinpoint the brain areas where different models of anxiety displayed the highest evidence. Behaviourally, we found that threat-of-shock eliminated the accuracy advantage conferred by environmental stability over volatility in the task at hand. Neurally, we found that threat-of-shock led to both attenuation and loss of volatility-attuning of neural activity evoked by surprising sounds across most subcortical and limbic brain regions including the thalamus, basal ganglia, claustrum, insula, anterior cingulate, hippocampal gyrus and also the superior temporal gyrus. Conversely, within two small clusters in the left medial frontal gyrus and extrastriate area, threat-of-shock boosted the neural activity (relative to the safe and volatile condition) to the levels observed during the safe and stable condition, while also inducing a loss of volatility-attuning. Taken together, our findings suggest that threat eliminates the learning advantage conferred by statistical stability compared to volatility. Thus, we propose that anxiety disrupts behavioural adaptation to environmental statistics, and that multiple subcortical and limbic regions are implicated in this process.

The Mere Sight of Loved Ones Does Not Inhibit Psychophysiological Defense Mechanisms When Threatened

Looking at pictures of loved ones, such as one's romantic partner or good friends, has been shown to alleviate the experience of pain and reduce defensive reactions. However, little is known about such modulatory effects on threat and safety learning and the psychophysiological processes involved. Here, we explored the hypothesis that beloved faces serve as implicit safety cues and attenuate the expression of fear responses and/or accelerate extinction learning in a threatening context. Thirty-two participants viewed pictures of their loved ones (romantic partner, parents, and best friend) as well as of unknown individuals within contextual background colors indicating threat-of-shock or safety. Focusing on the extinction of non-reinforced threat associations (no shocks were given), the experiment was repeated on two more test days while the defensive startle-EMG, SCR, and threat ratings were obtained. Results confirmed pronounced defensive responding to instructed threat-of-shock relative to safety context (e.g., threat-enhanced startle reflex and SCR). Moreover, threat-potentiated startle response slowly declined across test days indicating passive extinction learning in the absence of shocks. Importantly, neither a main effect of face category (loved vs. unknown) nor a significant interaction with threat/safety instructions was observed. Thus, a long-term learning history of beneficial relations (e.g., with supportive parents) did not interfere with verbal threat learning and aversive apprehensions.

Intolerance of uncertainty and physiological responses during instructed uncertain threat: a multi-lab investigation

Individuals with high self-reported Intolerance of uncertainty (IU) tend to interpret uncertainty negatively. Recent research has been inconclusive on evidence of an association between IU and physiological responses during instructed uncertain threat. To address this gap, we conducted secondary analyses of IU and physiology data recorded during instructed uncertain threat tasks from two lab sites (Wisconsin-Madison; n = 128; Yale, n = 103). Higher IU was associated with: (1) greater corrugator supercilii activity to predictable and unpredictable threat of shock, compared to the safety from shock, and (2) poorer discriminatory skin conductance response between the unpredictable threat of shock, relative to the safety from shock. No IU-related effects were observed for the orbicularis oculi. These findings suggest that IU-related biases may be captured differently depending on the physiological measure during instructed uncertain threat. Implications of these findings for neurobiological models of uncertainty and anticipation in anxiety are discussed.

Central stress allostasis among deprived and continuing marijuana users and non-users

Objective: We examined central nervous system stress allostasis (i.e., stress responses) among deprived and continuing heavy marijuana users and non-users. Method: Participants (N=210; 46.7% female; mean age=21.99; 91.4% White, 94.3% Non-Hispanic) were heavy marijuana users (N=134) and non-users (N=76). Heavy users were randomly assigned to a 3-day marijuana deprivation condition (N=68) or to continue using regularly (N=66). Participants completed 2 threat-of-shock stressor tasks that manipulated stressor predictability by varying shock probability or timing. We measured central stress allostasis via startle potentiation (stressor conditions minus matched no-stressor condition). We examined two group contrasts (heavy use: all heavy users vs. non-users; deprivation: deprived vs. continuing heavy users) on startle potentiation overall and moderated by stressor predictability (unpredictable vs. predictable). Results: Deprivation did not affect startle potentiation overall (timing task: p=0.184; probability task: p=0.328) or by stressor predictability (timing task: p=0.340; probability task: p=0.488). Heavy use did not affect startle potentiation overall (timing task: p=0.213; probability task: p=0.843) or by stressor predictability (timing task: p=0.683; probability task: p=0.348). Post-hoc analyses showed a general startle reactivity X deprivation interaction on startle potentiation overall (timing task: p=0.019; probability task: p=0.056) and by stressor predictability in the probability task (p=0.022) but not in the timing task (p=0.374). Conclusions: A history of marijuana use or acute deprivation did not alter central stress allostasis despite prominent theoretical expectations. This study adds to growing research on central stress allostasis in individuals with a history of drug use and begins to parse moderating roles of individual differences and stressor characteristics.

Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during cue-signalled uncertainty of threat

Heightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. We sought to determine whether individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during cue-signalled uncertainty of threat (n = 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings of arousal and valence, skin conductance response (SCR), and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat versus safe cues. IU was not associated with greater arousal ratings, SCR, or amygdala activation to uncertain threat versus safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat versus safe cues. These findings suggest that during cue-signalled uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with cue-signalled uncertainty of threat, which may be relevant to models of anxiety-related pathology.

Defensive freezing and its relation to approach–avoidance decision-making under threat

Successful responding to acutely threatening situations requires adequate approach–avoidance decisions. However, it is unclear how threat-induced states—like freezing-related bradycardia—impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach–avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia (high-vs-low threat) interacted with subjective value, depending on the action-context (passive-vs-active). Specifically, in action-contexts incongruent with participants’ intrinsic action-tendencies, stronger bradycardia related to diminished effects of subjective value on choice across participants. These findings illustrate the relevance of testing approach–avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach–avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach–avoidance decision-making.

Out of fright, out of mind: impaired memory for information negated during looming threat

People often need to update representations of information upon discovering them to be incorrect, a process that can be interrupted by competing cognitive demands. Because anxiety and stress can impair cognitive performance, we tested whether looming threat can similarly interfere with the process of updating representations of a statement’s truthfulness. On each trial, participants saw a face paired with a personality descriptor. Each pairing was followed by a signal indicating whether the pairing was “true”, or “false” (a negation of the truth of the statement), and this signal could be followed by a warning of imminent electric shock (i.e., the looming threat). As predicted, threat of shock left memory for “true” pairings intact, while impairing people’s ability to label negated pairings as untrue. Contrary to our predictions, the pattern of errors for pairings that were negated under threat suggested that these mistakes were at least partly attributable to participants forgetting that they saw the negated information at all (rather than being driven by miscategorization of the pairings as true). Consistent with this, linear ballistic accumulator modelling suggested that this impaired recognition stemmed from weaker memory traces rather than decisional processes. We suggest that arousal due to looming threat may interfere with executive processes important for resolving competition between mutually suppressive tags of whether representations in memory are “true” or “false”.

How Does Threat Modulate the Motivational Effects of Reward on Attention?

Studies on attentional bias have overwhelmingly focused on the priority of different stimuli and have rarely manipulated the state of the observer. Recently, the threat of unpredictable shock has been utilized to experimentally induce anxiety and investigate how negative arousal modulates attentional control. Experimentally induced anxiety has been shown to reduce the attentional priority afforded to reward-related stimuli while enhancing the efficiency of goal-directed attentional control. It is unclear which of these two influences might dominate when attending to reward-related stimuli is consistent with task goals and by extension what the scope of the modulatory influence of threat on attention is. In contrast to paradigms in the visual domain, a novel auditory identification task has demonstrated a robust influence of target-value associations on selective attention. In the present study, we examined how the threat of shock modulates the influence of learned value on voluntary attention. In both threat and no-threat conditions, we replicate prior findings of voluntary prioritization of reward-associated sounds. However, unlike in studies measuring involuntary attentional capture, threat did not modulate the influence of reward on attention. Our findings highlight important limitations to when and how threat modulates the control of attention, contextualizing prior findings.