Threat Of Shock Research Articles

Supplemental Material for Threat of Shock and Aversive Inhibition: Induced Anxiety Modulates Pavlovian-Instrumental Interactions

Supplemental Material for Threat of Shock and Aversive Inhibition: Induced Anxiety Modulates Pavlovian-Instrumental Interactions

Relationships among attention networks and physiological responding to threat

Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We attempted to resolve these conflicts by examining relationships of attentional abilities with responding to predictable and unpredictable threat – related but distinct motivational process implicated in a number of anxiety disorders. Eighty-one individuals completed a behavioral task assessing efficiency of three components of attention – alerting, orienting, and executive control (Attention Network Test - Revised). We also assessed startle responding during anticipation of both predictable, imminent threat (of mild electric shock) and unpredictable contextual threat. Faster alerting and slower disengaging from non-emotional attention cues were related to heightened responding to unpredictable threat, whereas poorer executive control of attention was related to heightened responding to predictable threat. This double dissociation helps to integrate models of attention and anxiety and may be informative for treatment development.

Clinical anxiety promotes excessive response inhibition.

Laboratory tasks to delineate anxiety disorder features are used to refine classification and inform our understanding of etiological mechanisms. The present study examines laboratory measures of response inhibition, specifically the inhibition of a pre-potent motor response, in clinical anxiety. Data on associations between anxiety and response inhibition remain inconsistent, perhaps because of dissociable effects of clinical anxiety and experimentally manipulated state anxiety. Few studies directly assess the independent and interacting effects of these two anxiety types (state v. disorder) on response inhibition. The current study accomplished this goal, by manipulating state anxiety in healthy and clinically anxious individuals while they complete a response inhibition task. The study employs the threat-of-shock paradigm, one of the best-established manipulations for robustly increasing state anxiety. Participants included 82 adults (41 healthy; 41 patients with an anxiety disorder). A go/nogo task with highly frequent go trials was administered during alternating periods of safety and shock threat. Signal detection theory was used to quantify response bias and signal-detection sensitivity. There were independent effects of anxiety and clinical anxiety on response inhibition. In both groups, heightened anxiety facilitated response inhibition, leading to reduced nogo commission errors. Compared with the healthy group, clinical anxiety was associated with excessive response inhibition and increased go omission errors in both the safe and threat conditions. Response inhibition and its impact on go omission errors appear to be a promising behavioral marker of clinical anxiety. These results have implications for a dimensional view of clinical anxiety.

Impact of Panic on Psychophysiological and Neural Reactivity to Unpredictable Threat in Depression and Anxiety.

Exaggerated anxious responding to unpredictable threat (U-threat) is a core feature of panic disorder (PD). However, it is unknown whether this abnormality is specific to the diagnosis of PD or would manifest along a continuum of panic symptomatology (PS). Additionally, little is known about the neural processes underlying this abnormality among those high in PS. Finally, no studies have tested whether startle potentiation and limbic neural reactivity - commonly used indices of U-threat responsivity - are associated and therefore reflect common abnormalities. These questions were investigated in 42 adults with a range of PS. U-threat responding was measured twice during threat-of-shock - once with startle and once with functional magnetic resonance imaging (fMRI). As hypothesized, PS positively predicted startle potentiation and dACC reactivity to U-threat. Startle potentiation and dACC activation to U-threat were positively associated. These results suggest a biobehavioral profile of aberrant responding to U-threat associated with PS.

Desperately Seeking Support

Much is unknown about adult attachment style formation. We investigate whether negative reinforcement schedules promote hallmark features of secure and anxious attachment styles in a shock threat support-seeking paradigm. Participants ostensibly asked for help from another participant seated in another room. Each time a shock threat signal appeared they were to press a button to indicate their need for help. The supporter could then stop the imminent shock. The reliability of the supporters was varied such that some supporters were consistent (continuous reinforcement) whereas others were inconsistent (variable ratio reinforcement). Results indicated that inconsistently responsive others, reinforcing on a variable ratio schedule, led to heightened approach-related attentional biases toward the supporter, measured by event-related potentials, increased positive attachment associations with the supporter, implicitly measured via a lexical decision task, and more negative explicit evaluations of the supporter.

Distinct Responses to Predictable and Unpredictable Threat in Anxiety Pathologies: Effect of Panic Attack

BackgroundDelineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in nonmedicated anxiety patients with and without a history of panic attacks (PAs). MethodsIn this study, 143 adults (72 healthy control subjects; 71 patients with generalized, social, or both generalized and social anxiety disorders, 24 with and 47 without PAs) were exposed to three conditions: 1) predictable shocks signaled by a cue, 2) unpredictable shocks, and 3) no shock. Startle magnitude was used to assess aversive responses. ResultsAcross disorders, a history of PAs was specifically associated with hypersensitivity to unpredictable threat. By disorder, social anxiety disorder was associated with hypersensitivity to predictable threat, whereas generalized anxiety disorder was associated with exaggerated baseline startle. ConclusionsThese results identified three physiological patterns. The first is hypersensitivity to unpredictable threat in individuals with PAs. The second is hypersensitivity to predictable threat, which characterizes social anxiety disorder. The third is enhanced baseline startle in generalized anxiety disorder, which may reflect propensity for self-generated anxious thoughts in the absence of imminent danger. These results inform current thinking by linking specific clinical features to particular physiology profiles.

The effects of methylphenidate and propranolol on the interplay between induced-anxiety and working memory.

Research documents a reciprocal impact of anxiety on working memory (WM), although its strength and direction depend on factors like task difficulty. A better understanding of these factors may generate insights into cognitive mechanisms of action involved in anxiety, culminating into treatment implications. By blocking the physiological effects of anxiety, propranolol might also block anxiety interference on WM. Conversely, by improving task-directed attention, methylphenidate might reduce anxiety, or, alternatively, by improving cognitive efficiency and free up processing resources to compute anxiety. To investigate the interplay between induced anxiety and WM, we pharmacologically manipulated either anxiety or cognition, using single doses of 40mg propranolol (PRO), 20mg methylphenidate (MPH), or placebo (PLA). In this double-blind parallel-group design study, 60 healthy volunteers (20/drug group) performed a verbal WM task under three loads, 1-, 2- and 3-back, and in two conditions, threat of shock and safety. Startle electromyography (EMG) was used to measure anxiety. Findings were twofold: (1) MPH blocked anxiety interference only on the 3-back WM performance, while PRO or PLA had no effects on anxiety-WM interference, and (2) drugs had no effects on anxiety, but, after controlling for baseline anxiety, MPH enhanced anxiety-potentiated startle during the 3-back task. These findings support that MPH-related improvement of cognitive efficiency permits anxiety to be processed and expressed. In conclusion, MPH may be a useful tool to investigate the mechanisms of interaction between anxiety and WM, particularly those under catecholaminergic control.

State anxiety carried over from prior threat increases late positive potential amplitude during an instructed emotion regulation task.

Emotion regulation has important consequences for emotional and mental health (Saxena, Dubey & Pandey, 2011) and is dependent on executive function (Eisenberg, Smith & Spinrad, 2011). Because state anxiety disrupts executive function (Robinson, Vytal, Cornwell & Grillon, 2013), we tested whether state anxiety disrupts emotion regulation by having participants complete an instructed emotion regulation task, while under threat of unpredictable shock and while safe from shock. We used the late positive potential (LPP) component of the event related potential to measure emotion regulation success. We predicted that LPP responses to negatively valenced images would be modulated by participants' attempts to increase and decrease their emotions when safe from shock, but not while under threat of shock. Our manipulation check revealed an order effect such that for participants who completed the threat of shock condition first self-reported state anxiety carried over into the subsequent safe condition. Additionally, we found that although instructions to regulate affected participants' ratings of how unpleasant the images made them feel, instructions to regulate had no effect on LPP amplitude regardless of threat condition. Instead we found that participants who received the threat condition prior to safe had greater LPP responses to all images in the safe condition. We posit that the carryover of anxiety resulted in misattribution of arousal and potentiation of neural responses to the images in the safe condition. Thus, our results imply that physiological arousal and cognition combine to influence the basic neural response to emotional stimuli. (PsycINFO Database Record

The neural basis of improved cognitive performance by threat of shock.

Anxiety can have both detrimental and facilitatory cognitive effects. This study investigates the neural substrates of a replicated facilitatory effect of anxiety on sustained attention and response inhibition. This effect consisted of improved performance on the Sustained Attention to Response Task (a Go-NoGo task consisting of 91% Go and 9% NoGo trials) in threat (unpredictable electrical shock) vs safe (no shock) conditions. This study uses the same experimental design with fMRI and relies on an event-related analysis of BOLD signal changes. Findings reveal that threat-related cognitive facilitation (improved NoGo accuracy) is associated with greater activation of a right-lateralized frontoparietal group of regions previously implicated in sustained attention and response inhibition. Moreover, these same regions show decreased activation in the Go trials preceding NoGo errors. During NoGo trials, striatal activity is also greater in the threat vs safe condition, consistent with the notion of enhanced inhibitory processing under threat. These findings identify potential mechanisms by which threat of unpredictable shock can facilitate distinct cognitive functions. A greater understanding of the complex interaction of the anxious state and cognitive processes may have critical clinical implications.

Anxiety-potentiated amygdala–medial frontal coupling and attentional control

Anxiety disorders can be treated both pharmacologically and psychologically, but many individuals either fail to respond to treatment or relapse. Improving outcomes is difficult, in part because we have incomplete understanding of the neurobiological mechanisms underlying current treatments. In a sequence of studies, we have identified ‘affective bias-related' amygdala–medial cortical coupling as a candidate substrate underlying adaptive anxiety (that is, anxiety elicited by threat of shock in healthy individuals) and shown that it is also chronically engaged in maladaptive anxiety disorders. We have provided evidence that this circuit can be modulated pharmacologically, but whether this mechanism can be shifted by simple psychological instruction is unknown. In this functional magnetic resonance imaging study, we extend a previously used translational anxiety induction (threat of shock) in healthy subjects (N=43) and cognitive task to include an element of instructed attentional control. Replicating our previous findings, we show that induced anxiety engages ‘affective bias-related' amygdala-dorsal medial frontal coupling during the processing of emotional faces. By contrast, instructing subjects to attend to neutral shapes (and ignore faces) disengages this circuitry and increases putative ‘attentional control-related' coupling between the amygdala and a more rostral prefrontal region. These neural coupling changes are accompanied by corresponding modulation of behavioural performance. Taken together, these findings serve to further highlight the potential role of amygdala–medial frontal coupling in the pathogenesis of anxiety and highlight a mechanism by which it can be modulated via psychological instructions. This, in turn, generates hypotheses for future work exploring the mechanisms underlying psychological therapeutic interventions for anxiety.

Anxiety Patients Show Reduced Working Memory Related dlPFC Activation During Safety and Threat.

Anxiety patients exhibit deficits in cognitive tasks that require prefrontal control of attention, including those that tap working memory (WM). However, it is unclear whether these deficits reflect threat-related processes or symptoms of the disorder. Here, we distinguish between these hypotheses by determining the effect of shock threat versus safety on the neural substrates of WM performance in anxiety patients and healthy controls. Patients, diagnosed with generalized and/or social anxiety disorder, and controls performed blocks of an N-back WM task during periods of safety and threat of shock. We recorded blood-oxygen-level dependent (BOLD) activity during the task, and investigated the effect of clinical anxiety (patients vs. controls) and threat on WM load-related BOLD activation. Behaviorally, patients showed an overall impairment in both accuracy and reaction time compared to controls, independent of threat. At the neural level, patients showed less WM load-related activation in the dorsolateral prefrontal cortex, a region critical for cognitive control. In addition, patients showed less WM load-related deactivation in the ventromedial prefrontal cortex and posterior cingulate cortex, which are regions of the default mode network. Most importantly, these effects were not modulated by threat. This work suggests that the cognitive deficits seen in anxiety patients may represent a key component of clinical anxiety, rather than a consequence of threat.

Anxiety promotes memory for mood-congruent faces but does not alter loss aversion.

Pathological anxiety is associated with disrupted cognitive processing, including working memory and decision-making. In healthy individuals, experimentally-induced state anxiety or high trait anxiety often results in the deployment of adaptive harm-avoidant behaviours. However, how these processes affect cognition is largely unknown. To investigate this question, we implemented a translational within-subjects anxiety induction, threat of shock, in healthy participants reporting a wide range of trait anxiety scores. Participants completed a gambling task, embedded within an emotional working memory task, with some blocks under unpredictable threat and others safe from shock. Relative to the safe condition, threat of shock improved recall of threat-congruent (fearful) face location, especially in highly trait anxious participants. This suggests that threat boosts working memory for mood-congruent stimuli in vulnerable individuals, mirroring memory biases in clinical anxiety. By contrast, Bayesian analysis indicated that gambling decisions were better explained by models that did not include threat or treat anxiety, suggesting that: (i) higher-level executive functions are robust to these anxiety manipulations; and (ii) decreased risk-taking may be specific to pathological anxiety. These findings provide insight into the complex interactions between trait anxiety, acute state anxiety and cognition, and may help understand the cognitive mechanisms underlying adaptive anxiety.

Cognitive trait anxiety, stress and effort interact to predict inhibitory control

ABSTRACTFew studies have focussed on the link between anxiety and inhibitory control in the absence of stimulus-driven external threat. This two-part experiment examined the interactions between (1) somatic trait anxiety, somatic situational stress (i.e. threat of electric shock), and effort, and (2) cognitive trait anxiety, cognitive situational stress (i.e. ego-threat instructions), and effort, on inhibitory processes using a Go-No-Go paradigm. Trait anxiety was operationalised using questionnaire scores and effort was operationalised using a visual analogue scale. Performance effectiveness was measured using the d′ parameter from signal detection theory and processing efficiency was indexed by the ratio of d′ to response time on correct trials. Results indicated that somatic trait anxiety and stress did not predict effectiveness or efficiency. Cognitive trait anxiety and stress were associated with both inhibitory effectiveness and efficiency deficits; however, contrary to expectations these deficits were evident at higher rather than lower mental effort. Results suggest a distinction between how somatic and cognitive anxiety manifest on tasks involving inhibitory control.

It's all in the anticipation: How perception of threat is enhanced in anxiety.

The importance of top-down factors such as goals and expectations is well-established in both visual perception and anxiety. However, researchers have attributed the perceptual prioritization of threatening stimuli in anxiety to bottom-up, automatic processing of these stimuli while neglecting the role of prestimulus, top-down factors. Furthermore, different kinds of anxiety (dispositional versus induced) impact cognitive functions differently, suggesting that top-down factors may have distinct effects on threat perception. In the present study, we examined whether prestimulus representations of threatening stimuli facilitate perception differently, depending on induced and trait anxiety. Two groups of participants completed a cued discrimination task using threatening or neutral cues to identify subsequently presented fearful and neutral faces, degraded to each participant's perceptual threshold. In Group 1, threat of shock induced anxiety (n = 22; 12 men), whereas in Group 2, no anxiety was induced (n = 29; 7 men). The impact of induced anxiety on perception interacted with trait anxiety. Following fear cues, higher trait anxiety was associated with improved perceptual sensitivity and faster reaction time under threat of shock, and worse perceptual sensitivity and slower reaction time in absence of shock. The present findings represent an important advance in the literature because they elucidate the role of previously ignored top-down factors in threat perception for individuals with varying levels of anxiety and highlight the distinct impact that different types of anxiety have on the perception of threatening stimuli. Furthermore, these findings underline the importance of including top-down factors in future conceptualizations of perceptual bias toward threat in anxiety.

Freezing promotes perception of coarse visual features.

Freezing is an evolutionarily preserved defensive behavior, characterized by immobility and heart rate deceleration, which is thought to promote visual perception. Rapid perceptual assessment of threat is crucial in life-threatening situations; for example, when policemen need to make split-second decisions about the use of deadly force. Here, we hypothesized that freezing is specifically associated with better perception of rapidly processed coarse, low-spatial frequency (LSF) features. We used a visual discrimination task in which participants determined the orientation of LSF and high-spatial frequency (HSF) gratings under threat of shock and safe conditions. As predicted, threat anticipation improved perception of LSF at the expense of HSF gratings. Crucially, stronger decrease in heart rate, a parasympathetic physiological index of freezing, was linked to better perception of LSF. These results provide empirical evidence for the comobilization of physiological and perceptual processes, which may play an important role in decision making under acute stress.

Effect of anxiety on behavioural pattern separation in humans

ABSTRACTBehavioural pattern separation (BPS), the ability to distinguish among similar stimuli based on subtle physical differences, has been used to study the mechanism underlying stimulus generalisation. Fear overgeneralisation is often observed in individuals with posttraumatic stress disorder and other anxiety disorders. However, the relationship between anxiety and BPS remains unclear. The purpose of this study was to determine the effect of anxiety (threat of shock) on BPS, which was assessed across separate encoding and retrieval sessions. Images were encoded/retrieved during blocks of threat or safety in a 2 × 2 factorial design. During retrieval, participants indicated whether images were new, old, or altered. Better accuracy was observed for altered images encoded during periods of threat compared to safety, but only if those images were also retrieved during periods of safety. These results suggest that overgeneralisation in anxiety may be due to altered pattern separation.

Functional Connectivity under Anticipation of Shock: Correlates of Trait Anxious Affect versus Induced Anxiety.

Sustained anxiety about potential future negative events is an important feature of anxiety disorders. In this study, we used a novel anticipation of shock paradigm to investigate individual differences in functional connectivity during prolonged threat of shock. We examined the correlates of between-participant differences in trait anxious affect and induced anxiety, where the latter reflects changes in self-reported anxiety resulting from the shock manipulation. Dissociable effects of trait anxious affect and induced anxiety were observed. Participants with high scores on a latent dimension of anxious affect showed less increase in ventromedial pFC-amygdala connectivity between periods of safety and shock anticipation. Meanwhile, lower levels of induced anxiety were linked to greater augmentation of dorsolateral pFC-anterior insula connectivity during shock anticipation. These findings suggest that ventromedial pFC-amygdala and dorsolateral pFC-insula networks might both contribute to regulation of sustained fear responses, with their recruitment varying independently across participants. The former might reflect an evolutionarily old mechanism for reducing fear or anxiety, whereas the latter might reflect a complementary mechanism by which cognitive control can be implemented to diminish fear responses generated due to anticipation of aversive stimuli or events. These two circuits might provide complementary, alternate targets for exploration in future pharmacological and cognitive intervention studies.

The impact of threat of shock on the framing effect and temporal discounting: executive functions unperturbed by acute stress?

Anxiety and stress-related disorders constitute a large global health burden, but are still poorly understood. Prior work has demonstrated clear impacts of stress upon basic cognitive function: biasing attention toward unexpected and potentially threatening information and instantiating a negative affective bias. However, the impact that these changes have on higher-order, executive, decision-making processes is unclear. In this study, we examined the impact of a translational within-subjects stress induction (threat of unpredictable shock) on two well-established executive decision-making biases: the framing effect (N = 83), and temporal discounting (N = 36). In both studies, we demonstrate (a) clear subjective effects of stress, and (b) clear executive decision-making biases but (c) no impact of stress on these decision-making biases. Indeed, Bayes factor analyses confirmed substantial preference for decision-making models that did not include stress. We posit that while stress may induce subjective mood change and alter low-level perceptual and action processes (Robinson et al., 2013c), some higher-level executive processes remain unperturbed by these impacts. As such, although stress can induce a transient affective biases and altered mood, these need not result in poor financial decision-making.

Behavioral assessment of risk-taking under uncertain threat: Associations with affect and pain tolerance

Low levels of risk-taking behavior have been associated with anxiety, but variables that influence risk-averse decision-making are not well-understood. Given that uncertainty is inherent to risk-taking behavior, individual differences in the appraisal of uncertainty (e.g., intolerance of uncertainty (IU)) may affect risk-taking behavior. However, nuanced behavioral assessments of risk-taking that allow for the simultaneous examination of uncertainty avoidance, risk-averse, and high-risk behavior are lacking. To address this gap in the literature, a computerized courage task was developed and the associations between task behavior and IU were examined. An unselected student sample completed measures of IU and other distress intolerance constructs before completing a cold pressor task to behaviorally assess pain tolerance and the courage task in which they were asked to win money under threat of possible shock. Selecting larger amounts of money was associated with greater risk of shock; a ‘pass’ option to avoid choosing entirely, ensuring no shock or money, was provided every trial. Self-reported anxious reactivity was related to lower-risk monetary choices, whereas greater IU was incrementally related specifically to pass choices; IU was unrelated to pain tolerance. Results support IU's construct validity and suggest that it may have incremental utility for understanding risk-taking behavior in anxiety disorders.

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson's Disease.

BackgroundParadoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls.MethodsParticipants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure.ResultsOn trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings.ConclusionsWhen motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson’s disease.