Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety

Abstract

In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para-hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat.

Keywords: amygdala; dmPFC; functional connectivity; precuneus; trait anxiety; uncertainty and anticipation model of anxiety (UAMA).

Figure 1

Task design. The paradigm presented to subjects during fMRI scanning. In each trial, subjects viewed an “X” (negative anticipation) or “O” (uncertain anticipation) or “?” (neutral anticipation) for 2 s, followed by a 2–8 s ISI, then, for “X” or “O”, followed by an aversive picture or neutral picture in a 100% for 2 s, for “?”, followed by either an aversive or neutral picture at exactly a 50/50 ratio for 2 s, finally a 2–8 s ISI following [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Brain systems showing significant main effect of uncertainty. Representative clusters show significant activation (coded in red) during contrasting between uncertain condition and certain condition, color bar represents T values. Parameter estimates of uncertain condition and certain condition for the high anxiety (coded in red) and low anxiety (coded in blue) group. Notes: HA, high anxiety; LA, low anxiety; a.u., arbitrary units; dmPFC, dorso‐medial prefrontal cortex; IFG, inferior frontal gyrus; Prec, precuneus; Ins, insula; Hippo, hippocampus; MTG, middle temporal gyrus; MOG, middle occipital gyrus. Error bars, SEM [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Brain systems showing significant main effects of trait anxiety. Representative clusters show significant activation (coded in red) during contrasting between the high anxiety group and low anxiety group across anticipation conditions, color bar represents T values. Parameter estimates of uncertain condition and certain condition for the high anxiety (coded in red) and low anxiety (coded in blue) group. Notes: HA, high anxiety; LA, low anxiety; a.u., arbitrary units; dlPFC, dorso‐lateral prefrontal cortex; IPS, inferior parietal sulcus; PHA, para‐hippocampus; L, left; R, right. Error bars, SEM [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Correlation between activation of regions in the main effects of group and trait anxiety levels. Brain activation in the main effects of group versus trait anxiety scores. For each column, correlations were showed for uncertain condition (upper) and certain condition (lower). In each panel, the solid lines represent linear fitting of the correlation, the shadows indicate one standard error. Notes: MFG, middle frontal gyrus (dorso‐lateral prefrontal cortex); IPS, inferior parietal sulcus; PHA, para‐hippocampus; L, left; R, right [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Brain regions showing significant interaction effect between anticipation conditions and anxiety groups. Representative clusters show significant activation (coded in red) in interaction contrast, color bar represents T values. Parameter estimates of uncertain condition and certain condition for the high anxiety (coded in red) and low anxiety (coded in blue) group. Notes: HA, high anxiety; LA, low anxiety; a.u., arbitrary units; dmPFC, dorso‐medial prefrontal cortex; Prec, precuneus; MTG, middle temporal gyrus; L, left; R, right. Error bars, SEM [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 6

Correlation between activation of regions in the interaction effects and trait anxiety levels. Brain activation in the interaction effects versus trait anxiety scores. For each column, correlations were showed for uncertain condition (upper) and certain condition (lower). The solid lines represent linear fitting of the correlation, the shadows indicate one standard error. Notes: Notes: HA, high anxiety; LA, low anxiety; dmPFC, dorso‐medial prefrontal cortex; Prec, precuneus; MTG, middle temporal gyrus; L, left; R, right [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 7

Brain region showing significant functional connectivity with amygdala in interaction effect between anticipation conditions and anxiety groups. (a) Representative clusters show significant connection with amygdala. (b) Parameter estimates of uncertain condition and certain condition for the high anxiety (coded in red) and low anxiety (coded in blue) group. Notes: HA, high anxiety; LA, low anxiety; dlPFC, dorso‐lateral prefrontal cortex; STG, superior temporal gyrus; IOL, inferior occipital lobe. Error bars, SEM [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 8

Correlation between amygdala‐related connectivity and trait anxiety levels. Brain connectivity versus trait anxiety scores. For each column, correlations were showed for uncertain condition (upper) and certain condition (lower). The solid lines represent linear fitting of the correlation, the shadows indicate one standard error. Notes: HA, high anxiety; LA, low anxiety; dlPFC, dorso‐lateral prefrontal cortex; STG, superior temporal gyrus; IOL, inferior occipital lobe [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 9

Brain region showing significant functional connectivity with dmPFC in interaction effect between anticipation conditions and anxiety groups. (a) Representative clusters show significant connection with dmPFC. (b) Parameter estimates of uncertain condition and certain condition for the high anxiety (coded in red) and low anxiety (coded in blue) group. Notes: HA, high anxiety; LA, low anxiety; a.u., arbitrary units; dmPFC, dorso‐medial prefrontal cortex; vmPFC, ventral‐medial prefrontal cortex. Error bars, SEM [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 10

Brain systems showing significant functional connectivity with precuneus in interaction effect between anticipation conditions and anxiety groups. (a) Representative clusters show significant connection with precuneus. (b) Parameter estimates of uncertain condition and certain condition for the high anxiety (coded in red) and low anxiety (coded in blue) group. Notes: HA, high anxiety; LA, low anxiety; a.u., arbitrary units; Prec, precuneus; dlPFC, dorso‐lateral prefrontal cortex; IPS, inferior parietal sulcus; Ins, insula; PHA, para‐hippocampus; MTG, middle temporal gyrus; L, left; R, right. Error bars, SEM [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 11

Correlation between dmPFC‐related and precuneus‐related connectivity and trait anxiety levels. Brain connectivity versus trait anxiety scores. For each column, correlations were showed for uncertain condition (upper) and certain condition (lower). The solid lines represent linear fitting of the correlation, the shadows indicate one standard error. Notes: Notes: HA, high anxiety; LA, low anxiety; dmPFC, dorso‐medial prefrontal cortex; vmPFC, ventral‐medial prefrontal cortex; Prec, precuneus; dlPFC, dorso‐lateral prefrontal cortex; IPS, inferior parietal sulcus; Ins, insula; PHA, para‐hippocampus; MTG, middle temporal gyrus; L, left; R, right [Color figure can be viewed at http://wileyonlinelibrary.com]