Dataset Information

The relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms.

ABSTRACT: Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and overwhelming anxiety about when another attack may strike. Patients with panic disorder and healthy individuals with a history of panic attacks show a hypersensitivity to unpredictable threats, suggesting a possible link between panic and sustained anxiety. The purpose of this study was to determine the degree to which induced symptoms of panic relate to fear and anxiety, as well as activity in the neural systems that mediate and regulate these affective states. Psychological and physiological symptoms of panic were assessed during an 8-min 7.5% CO2 challenge task. Psychological, physiological, and neural symptoms of fear and anxiety were measured during two sessions (one psychophysiology and one functional magnetic resonance imaging where subjects experienced several blocks of no threat (N), predictable shock (P), and unpredictable shock (U; NPU threat task). We used a principle component analysis to characterize panic susceptibility (PS), and found that PS significantly predicted dorsolateral prefrontal cortex (dlPFC) activity to the unpredictable cue during the NPU threat task. When examining the weighted beta coefficients from this analysis, we observed that self-reported fear/anxiety during the CO2 challenge negatively loaded onto dlPFC activity during the NPU task. Consistent with this observation, dlPFC activity during the unpredictable cue was also negatively correlated with anxiety during the NPU sessions. Together, these results suggest that panic symptoms and anxiety are regulated by the same prefrontal cognitive control system.

SUBMITTER: Balderston NL

PROVIDER: S-EPMC5802456 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The relationship between dlPFC activity during unpredictable threat and CO<sub>2</sub>-induced panic symptoms.

Balderston Nicholas L NL Liu Jeffrey J Roberson-Nay Roxann R Ernst Monique M Grillon Christian C

Translational psychiatry 20171130 12

Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and overwhelming anxiety about when another attack may strike. Patients with panic disorder and healthy individuals with a history of panic attacks show a hypersensitivity to unpredictable threats, suggesting a possible link between panic and sustained anxiety. The purpose of this study was to determine the degree to which induced symptoms of panic relate to fear and anxiety, as well as activity in the ne ...[more]

PMID: 29213110

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Project description:It has long been established that individuals with anxiety disorders tend to overgeneralize attributes of fearful stimuli to nonfearful stimuli, but there is little mechanistic understanding of the neural system that supports overgeneralization. To address this gap in our knowledge, this study examined effect of experimentally induced anxiety in humans on generalization using the behavioral pattern separation (BPS) paradigm. Healthy subjects of both sexes encoded and retrieved novel objects during periods of safety and threat of unpredictable shocks while we recorded brain activity with fMRI. During retrieval, subjects were instructed to differentiate among new, old, and altered images. We hypothesized that the hippocampus and dorsolateral prefrontal cortex (dlPFC) would play a key role in the effect of anxiety on BPS. The dlPFC, but not the hippocampus, showed increased activity for altered images compared with old images when retrieval occurred during periods of threat compared with safety. In addition, accuracy for altered items retrieved during threat was correlated with dlPFC activity. Together, these results suggest that overgeneralization in anxiety patients may be mediated by an inability to recruit the dlPFC, which mediates the cognitive control needed to overcome anxiety and differentiate between old and altered items during periods of threat.SIGNIFICANCE STATEMENT Anxiety and posttraumatic stress disorder patients generalize fear to nonfearful fear stimuli, making it difficult to regulate anxiety. Understanding how anxiety affects generalization is key to understanding the overgeneralization experienced by these patients. We examined this relationship in healthy subjects by studying how threat of shock affects neural responses to previously encountered stimuli. Although previous studies point to hippocampal involvement, we found that threat affected activity in the dorsolateral prefrontal cortex (dlPFC), rather than the hippocampus, when subjects encountered slightly altered versions of the previously encountered items. Importantly, this dlPFC activity predicted performance for these items. Together, these results suggest that the dlPFC is important for discrimination during elevated anxiety and that overgeneralization may reflect a deficit in dlPFC-mediated cognitive control.

Dataset Information

The relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms.

Publications

The relationship between dlPFC activity during unpredictable threat and CO<sub>2</sub>-induced panic symptoms.

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