Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test)

Schmitz, Anja; Grillon, Christian

doi:10.1038/nprot.2012.001

Cited by 338 publications

(432 citation statements)

References 34 publications

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“…As such, there is considerable flexibility in cue-shock contingencies and shock characteristics that can support a program of research with strong conceptual replications. For example, the Threat Probability Task is a derivative of the previously validated No-Shock, Predictable Shock, Unpredictable shock task 21 . The NPU task manipulates uncertainty regarding both IF (shock probability) and WHEN (shock timing) shocks will occur.…”

Section: Discussionmentioning

confidence: 99%

“…The Threat Probability Task was inspired by Grillon and colleagues when these researchers introduced the use of startle potentiation to study anxiety and fear in humans with the No-shock, Predictable-shock, Unpredictable-shock (NPU) task 21 . In the Predictable condition of the NPU task, shocks are 100 percent cue-contingent and occur at a consistent, known time (end of brief cue presentation).…”

Section: Translational Research With Animals Using the Startle Responsementioning

confidence: 99%

“…Calculate startle potentiation for uncertain shock as the difference between mean startle response to startle probes during 20% shock cues vs. no-shock cues (see Figure 6B). NOTE: Startle response to ITI probes during the 20% condition can also be measured to study effects of anticipation and sustained startle potentiation relevant to some conceptualizations of anxiety 6,21 . 2.…”

Section: Rectify the Filtered Continuous Emg (Seementioning

confidence: 99%

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Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat

Bradford

Magruder

Korhumel

et al. 2014

JoVE

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Fear of certain threat and anxiety about uncertain threat are distinct emotions with unique behavioral, cognitive-attentional, and neuroanatomical components. Both anxiety and fear can be studied in the laboratory by measuring the potentiation of the startle reflex. The startle reflex is a defensive reflex that is potentiated when an organism is threatened and the need for defense is high. The startle reflex is assessed via electromyography (EMG) in the orbicularis oculi muscle elicited by brief, intense, bursts of acoustic white noise (i.e., "startle probes"). Startle potentiation is calculated as the increase in startle response magnitude during presentation of sets of visual threat cues that signal delivery of mild electric shock relative to sets of matched cues that signal the absence of shock (no-threat cues). In the Threat Probability Task, fear is measured via startle potentiation to high probability (100% cue-contingent shock; certain) threat cues whereas anxiety is measured via startle potentiation to low probability (20% cue-contingent shock; uncertain) threat cues. Measurement of startle potentiation during the Threat Probability Task provides an objective and easily implemented alternative to assessment of negative affect via self-report or other methods (e.g., neuroimaging) that may be inappropriate or impractical for some researchers. Startle potentiation has been studied rigorously in both animals (e.g., rodents, non-human primates) and humans which facilitates animal-to-human translational research. Startle potentiation during certain and uncertain threat provides an objective measure of negative affective and distinct emotional states (fear, anxiety) to use in research on psychopathology, substance use/abuse and broadly in affective science. As such, it has been used extensively by clinical scientists interested in psychopathology etiology and by affective scientists interested in individual differences in emotion. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

Section: Translational Research With Animals Using the Startle Responsementioning

confidence: 99%

Section: Rectify the Filtered Continuous Emg (Seementioning

confidence: 99%

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Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat

Bradford

Magruder

Korhumel

et al. 2014

JoVE

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“…Therefore, the most direct translation from rodent paradigms to human research is anticipation of shock tasks that have been used in several studies. As one example, the NPU-threat task (no-shock/predictable-shock/unpredictableshock task) developed by the Grillon lab (Schmitz and Grillon, 2012) manipulates threat context to elicit safety, fear, and anxiety responses, respectively. In the no-shock/safe condition, no shocks are administered in a particular context, providing a baseline measure.…”

Section: Bnst Function During Anticipation Of Threatmentioning

confidence: 99%

The Human BNST: Functional Role in Anxiety and Addiction

Avery

Clauss

Blackford

2015

Neuropsychopharmacol

285

206

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The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region-the bed nucleus of the stria terminalis (BNST)-in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stressrelated disorders and identify novel neural targets for treatment.

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“…It also should be noted that we did not acquire physiological responses in this study (e.g., heart rate or skin conductance). The stress paradigm was adapted from a well-validated psychophysiological threat paradigm that reliably increases physiological concomitants of stress and anxiety (26), but acquisition of such variables in future research would be valuable.…”

Section: Fig 1 (A)mentioning

confidence: 99%

Stress increases aversive prediction error signal in the ventral striatum

Robinson

Overstreet

Charney

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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From job interviews to the heat of battle, it is evident that people think and learn differently when stressed. In fact, learning under stress may have long-term consequences; stress facilitates aversive conditioning and associations learned during extreme stress may result in debilitating emotional responses in posttraumatic stress disorder. The mechanisms underpinning such stress-related associations, however, are unknown. Computational neuroscience has successfully characterized several mechanisms critical for associative learning under normative conditions. One such mechanism, the detection of a mismatch between expected and observed outcomes within the ventral striatum (i.e., "prediction errors"), is thought to be a critical precursor to the formation of new stimulusoutcome associations. An untested possibility, therefore, is that stress may affect learning via modulation of this mechanism. Here we combine a translational model of stress with a cognitive neuroimaging paradigm to demonstrate that stress significantly increases ventral striatum aversive (but not appetitive) prediction error signal. This provides a unique account of the propensity to form threat-related associations under stress with direct implications for our understanding of both normal stress and stress-related disorders.threat of shock | punishment | anxiety | face perception L earning to associate cues with threat is adaptive because it allows future threat to be predicted and avoided (1). However, such associative learning also may lead to haunting and debilitating memories; the smell of stir-fry may evoke painful intrusive memories in Vietnam veterans. How aversive information is integrated to guide adaptive or maladaptive behavior, however, is not well understood. Here, we report that stress increases a key learning mechanism: the neural detection of a mismatch between an expected and observed aversive outcome within the ventral striatum, commonly referred to as the aversive prediction error (PE) signal (1, 2).Neurocomputational and neuroeconomic accounts of cognition posit that stimulus-outcome associations during conditioning are formed via temporal difference learning (1, 3, 4), in which learning depends upon comparing expectation to what is currently happening. New associations, it is argued, are driven by a difference between predicted and actual outcomes (i.e., "prediction errors"), with greater mismatch between expected and actual outcomes evoking greater PE, resulting in greater predictive learning. This mismatch gives rise to phasic dopamine release in the ventral striatum (1, 3-5) for both appetitive and aversive stimuli (1, 2, 6, 7). Little is known, however, about how PE processing might be affected by an organism's emotional state. Stress, for instance, is well known to facilitate aversive conditioning in both humans and animals (8, 9), raising the possibility that aversive PEs also might be increased by stress. This hypothesis, however, is untested. Therefore, here we used a translational stress induction method in healt...

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Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test)

Cited by 338 publications

References 34 publications

Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat

Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat

The Human BNST: Functional Role in Anxiety and Addiction

Stress increases aversive prediction error signal in the ventral striatum

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