State anxiety modulation of the amygdala response to unattended threat-related stimuli

Abstract

Findings from fear-conditioning studies in rats and functional neuroimaging with human volunteers have led to the suggestion that the amygdala is involved in the preattentive detection of threat-related stimuli. However, some neuroimaging findings point to attentional modulation of the amygdala response. The clinical-cognitive literature suggests that the extent to which the processing of threat-related stimuli is modulated by attention is crucially dependent on participants' anxiety levels. Here, we conducted a functional magnetic resonance imaging study with 27 healthy volunteers to examine whether amygdala responsivity to unattended threat-related stimuli varies with individual differences in state anxiety. Pairs of houses and faces (both fearful or neutral in expression) were presented, and participants attended to either the faces or the houses and matched these stimuli on identity. "Low-anxious" participants showed a reduced amygdala response to unattended versus attended fearful faces, but "high-anxious" participants showed no such reduction, having an increased amygdala response to fearful versus neutral faces regardless of attentional focus. These findings suggest that anxiety may interact with attentional focus to determine the magnitude of the amygdala response to threat-related stimuli.

Figure 1.

Example stimuli. On each trial, two faces and two houses were presented in vertical and horizontal pairs around a central fixation cross. Participants matched either faces or houses, as cued by spatial location. Faces could differ in identity, but both were always either neutral or fearful in expression. Face stimuli copyright Paul Ekman [Ekman and Friesen (1976), reprinted with permission].

Figure 2.

Amygdala activity to fearful versus neutral faces against participant state anxiety. A, Left and right amygdala ROIs (volume of each, 46 voxels, 368 mm³). Clusters extracted from analysis of localizer task data. B, Within the left amygdala ROI, the mean signal change (percentage of whole brain signal intensity) associated with the fearful versus neutral face contrast showed a positive relationship with participant state anxiety. This relationship is plotted for the peak voxel within the ROI (x, y, z =-14, -8, -22; Z = 2.48; p corrected <0.05).

Figure 3.

Anxiety influences attentional modulation of amygdala activity to fearful versus neutral faces. A, Amygdala activity to attended fearful (AF) faces versus attended neutral (AN) faces relative to unattended fearful (UF) faces versus unattended neutral (UN) faces against STAI state anxiety. Activation plotted is mean percentage signal change associated with this contrast for the peak voxel from the left amygdala ROI (x,y,z = -18, -10, -20; Z = 2.80; p corrected <0.02). A trend toward a similar relationship was observed with in the right amygdala ROI (x, y, z = 26, -12, -18; Z = 2.05; p corrected = 0.10). B, Amygdala activity to fearful versus neutral faces by attentional condition and anxiety level. Participants were divided into low- and high-anxious groups using a median split on STAI state anxiety scores. Amygdala activity is mean percentage signal change for the peak voxel from A.