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Comparative Study
. 2007 Jun 6;27(23):6313-9.
doi: 10.1523/JNEUROSCI.5369-06.2007.

Cerebral Blood Flow in Immediate and Sustained Anxiety

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Free PMC article
Comparative Study

Cerebral Blood Flow in Immediate and Sustained Anxiety

Gregor Hasler et al. J Neurosci. .
Free PMC article

Abstract

The goal of this study was to compare cerebral blood flow (CBF) changes associated with phasic cued fear versus those associated with sustained contextual anxiety. Positron emission tomography images of CBF were acquired using [O-15]H2O in 17 healthy human subjects as they anticipated unpleasant electric shocks that were administered predictably (signaled by a visual cue) or unpredictably (threatened by the context). Presentation of the cue in either threat condition was associated with increased CBF in the left amygdala. A cue that specifically predicted the shock was associated with CBF increases in the ventral prefrontal cortex (PFC), hypothalamus, anterior cingulate cortex, left insula, and bilateral putamen. The sustained threat context increased CBF in the right hippocampus, mid-cingulate gyrus, subgenual PFC, midbrain periaqueductal gray, thalamus, bilateral ventral striatum, and parieto-occipital cortex. This study showed distinct neuronal networks involved in cued fear and contextual anxiety underlying the importance of this distinction for studies on the pathophysiology of anxiety disorders.

Figures

Figure 1.
Figure 1.
Example of CBF image acquisition trial. Each trial followed an instructed threat procedure in which one of three conditions (N, P, or U) was presented for ∼1.5 min. Each condition was preceded and followed by 30 s of filler that was not included in analyses. In the N condition, no unpleasant events (shocks) were delivered. In the P condition (shown), unpleasant events were administered only in the presence of a threat cue. In the U condition, unpleasant events were delivered at any time. During each trial, two 10-s-duration cues were presented. Cues consisted of different colored shapes (color omitted here). The cues signaled the possibility of receiving an aversive stimulus in the P condition but had no signal value in the other conditions. Throughout each trial, a computer monitor apprised participants of the current condition by displaying one of the following messages: “No Unpleasant Event” (neutral), “Unpleasant Event Only During Red Square” (predictable), or “Unpleasant Event at Any Time” (unpredictable). This information, in the absence of a cue, constituted the context for each condition. One shock was administered during each trial involving a P or U condition. The shocks were delivered simultaneously with the offset of a cue in the P condition and in the absence of the cue in the U condition. Two CBF images were acquired in each condition: one when the cue was displayed along with the instructions and another when the cue was absent (i.e., during the context only). Thus, one CBF scan was acquired per trial.
Figure 2.
Figure 2.
Self-reported anxiety levels classified by condition (N, P, U) and stimulus (cue, context).
Figure 3.
Figure 3.
Merged PET–MRI sections illustrating CBF increases in mesiotemporal brain structures displayed on a canonical brain. A, CBF activations during the cue predicting an electric shock at p < 0.005. B, CBF activations during the threat context at p < 0.005

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