using-threat-probability-task-to-assess-anxiety-fear-during-uncertain

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

Fear of certain threat and anxiety about uncertain threat are distinct emotions with unique behavioral, cognitive-attentional, and neuroanatomical ...

University of Wisconsin-Madison

Classical fear-conditioning is central to many etiologic accounts of panic disorder (PD), but few lab-based conditioning studies in PD have been conducted. One conditioning perspective proposes associative-learning deficits characterized by deficient safety learning among PD patients. The current study of PD assesses acquisition and retention of discriminative aversive conditioning using a fear-potentiated startle paradigm. This paradigm was chosen for its specific capacity to independently assess safety- and danger learning in the service of characterizing putative anomalies in each type of learning among those with PD. Though no group difference in fear-potentiated startle was found at retention, acquisition results demonstrate impaired discriminative learning among PD patients as indexed by measures of conditioned startle-potentiation to learned safety and danger cues. Importantly, this discrimination deficit was driven by enhanced startle-potentiation to the learned safety cue rather than aberrant reactivity to the danger cue. Consistent with this finding, PD patients relative to healthy individuals reported higher expectancies of dangerous outcomes in the presence of the safety cue, but equal danger expectancies during exposure to the danger cue. Such results link PD to impaired discrimination learning, reflecting elevated fear responding to learned safety cues.

Impaired discriminative fear-conditioning resulting from elevated fear responding to learned safety cues among individuals with panic disorder.

Recent research on classical fear-conditioning in the anxiety disorders has identified overgeneralization of conditioned fear as an important conditioning correlate of anxiety pathology. Unfortunately, only one human neuroimaging study of classically conditioned fear generalization has been conducted, and the neural substrates of this clinically germane process remain largely unknown. The current generalization study employs a clinically validated generalization gradient paradigm, modified for the fMRI environment, to identify neural substrates of classically conditioned generalization that may function aberrantly in clinical anxiety. Stimuli include five rings of gradually increasing size with extreme sizes serving as cues of conditioned danger (CS+) and safety (CS-). The three intermediately sized rings serve as generalization stimuli (GSs) and create a continuum-of-size from CS+ to CS-. Results demonstrate 'positive' generalization gradients, reflected by declines in responding as the presented stimulus differentiates from CS+, in bilateral anterior insula, dorsomedial prefrontal cortex, and bilateral inferior parietal lobule. Conversely, 'negative' gradients, reflected by inclines in responding as the presented stimulus differentiates from CS+ were instantiated in bilateral ventral hippocampus, ventromedial prefrontal cortex and precuneus cortex. These results as well as those from connectivity analyses are discussed in relation to a working neurobiology of conditioned generalization centered on the hippocampus.

Neural substrates of classically conditioned fear-generalization in humans: a parametric fMRI study.

Stress response dampening is an important motive for alcohol use. However, stress reduction via alcohol (alcohol SRD) is observed inconsistently in the laboratory, and this has raised questions about the precise mechanisms and boundary conditions for these effects. Emerging evidence indicates that alcohol SRD may be observed selectively during uncertain but not certain threats. In a final sample of 89 participants, we measured stress response via potentiation of defensive startle reflex in response to threat of shock in blocks with certain (low and high) and uncertain shock intensity. Our alcohol-administration procedure produced blood alcohol concentrations (BACs) across a broad range (0.00%-0.12%) across participants. Increasing BACs were associated with linearly decreasing startle potentiation and self-reported anxiety. This SRD effect was greater during uncertain than certain threat. More broadly, these results suggest that distinct mechanisms are involved in response to threats of uncertain intensity and threats of certain intensity.

How bad could it be? Alcohol dampens stress responses to threat of uncertain intensity.

General startle reactivity reflects defensive reactivity independent of affective foreground. We examined the relationship between general startle reactivity and startle response to threat in three tasks with distinct manipulations of threat uncertainty. General startle reactivity was a stronger predictor of startle response during threat (vs. no threat) and uncertain (vs. certain threat). These results confirm that including general startle reactivity in our analyses can increase the power and/or precision to test effects of other focal experimental manipulations or grouping variables. Moreover, this suggests that individual differences in defensive reactivity moderate responding to threats of various types in our environment. As such, individual differences in general startle reactivity may index important psychological attributes related to trait affectivity, premorbid vulnerability for psychopathology, and manifest psychopathology.

Article	Year
Impaired discriminative fear-conditioning resulting from elevated fear responding to learned safety cues among individuals with panic disorder. Behaviour research and therapy\| PubMed ID: 19027893	2009
Neural substrates of classically conditioned fear-generalization in humans: a parametric fMRI study. Social cognitive and affective neuroscience\| PubMed ID: 23748500	2014
How bad could it be? Alcohol dampens stress responses to threat of uncertain intensity. Psychological science\| PubMed ID: 24145332	2013
Not just noise: individual differences in general startle reactivity predict startle response to uncertain and certain threat. Psychophysiology\| PubMed ID: 24611542	2014

Daniel E. Bradford

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