Experiential, autonomic, and neural responses during threat anticipation vary as a function of threat intensity and neuroticism

Abstract

Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses.

Figure 1

Study 1: Effects of shock anticipation on (A) continuous ratings of anxiety and (B) skin conductance response across three levels of shock intensity. Paired t-tests indicated significant differences between the conditions for both (A) and (B) (all ps < .001). Error bars = SEM.

Figure 1

Study 1: Effects of shock anticipation on (A) continuous ratings of anxiety and (B) skin conductance response across three levels of shock intensity. Paired t-tests indicated significant differences between the conditions for both (A) and (B) (all ps < .001). Error bars = SEM.

Figure 2

Study 1: The effect of neuroticism (median split) on continuous ratings of anxiety. Repeated-measures ANOVAs showed a significant effect of neuroticism on anxiety ratings (p=.004).

Figure 3

Study 2: Effects of shock anticipation on neural responses for (A) the contrast shock anticipation > safe (starting top left and moving clockwise, slices are displayed at x=36, x=0, z=40 , z=11) and (B) the conjunction analysis with strong shock anticipation > medium shock anticipation (top slice is displayed at x=0, bottom slice at z=11). Contrasts displayed at corrected p<.05, t=3.5, color bar indicates t statistic. Coordinates for all regions showing a main effect of shock anticipation are displayed in Table 1.

Figure 4

Study 2: Neural response to threat varies as a function of neuroticism. (A) the relationship between BOLD response to each condition and neuroticism (median split) in right BA 46 (brain slice depicted in (B), the contrast strong shock anticipation > medium shock anticipation). Regions which correlate with neuroticism for the contrast strong shock anticipation > medium shock anticipation, using a whole-brain regression at corrected p < .05, T=3.5, color bar indicates R² value: (B) right BA 46 (anterior cluster; x=-3, y=-4, z=53), (C) right insula (x=45, y=13, z=22). Coordinates for regions showing a significant correlation with neuroticism are displayed in Table 2.

Figure 4

Study 2: Neural response to threat varies as a function of neuroticism. (A) the relationship between BOLD response to each condition and neuroticism (median split) in right BA 46 (brain slice depicted in (B), the contrast strong shock anticipation > medium shock anticipation). Regions which correlate with neuroticism for the contrast strong shock anticipation > medium shock anticipation, using a whole-brain regression at corrected p < .05, T=3.5, color bar indicates R² value: (B) right BA 46 (anterior cluster; x=-3, y=-4, z=53), (C) right insula (x=45, y=13, z=22). Coordinates for regions showing a significant correlation with neuroticism are displayed in Table 2.