Social anxiety is associated with BNST response to unpredictability

Abstract

Background: Anxiety disorders are highly prevalent and cause substantial suffering and impairment. Whereas the amygdala has well-established contributions to anxiety, evidence from rodent and nonhuman primate models suggests that the bed nucleus of the stria terminalis (BNST) may play a critical, and possibly distinct, role in human anxiety disorders. The BNST mediates hypervigilance and anticipatory anxiety in response to an unpredictable or ambiguous threat, core symptoms of social anxiety, yet little is known about the BNST's role in social anxiety.

Methods: Functional magnetic resonance imaging was used to measure neural responses during a cued anticipation task with an unpredictable, predictable threat, and predictable neutral cues followed by threat or neutral images. Social anxiety was examined using a dimensional approach (N = 44 adults).

Results: For unpredictable cues, higher social anxiety was associated with lower BNST-amygdala connectivity. For unpredictable images, higher social anxiety was associated with greater connectivity between the BNST and both the ventromedial prefrontal cortex and the posterior cingulate cortex and lower connectivity between the BNST and postcentral gyrus. Social anxiety moderated the BNST-amygdala dissociation for unpredictable images; higher social anxiety was associated with BNST > amygdala response to unpredictable threat relative to unpredictable neutral images.

Conclusions: Social anxiety was associated with alterations in BNST responses to unpredictability, particularly in the BNST's interactions with other brain regions, including the amygdala and prefrontal cortex. To our knowledge, these findings provide the first evidence for the BNST's role in social anxiety, which may be a potential new target for prevention and intervention.

Keywords: BST, amygdala, anxiety, fMRI, uncertainty.

Figure 1.

BNST activation to cues and images. Left: The BNST shows significantly higher activation to unpredictable threat cues relative to predictable threat and predictable neutral cues (p < .05). Right: BNST response is consistently similar to baseline across all image conditions, with no significant effect of image type or valence. Horizontal lines indicate significant group differences.

Figure 2.. Social anxiety moderates BNST task-related connectivity to cues and images.

In the brain images, regions in blue represent negative correlations and regions in yellow represent positive correlations. The scatterplots illustrate the correlations with social anxiety by cue type, image valence, or image type; connectivity values were extracted from the significant clusters. Brain regions are labelled: dACC = dorsal anterior cingulate cortex; vmPFC = ventromedial prefrontal cortex; PCG = post-central gyrus; PCC = posterior cingulate cortex. The hemisphere of the seed region is indicated by text (L BNST or R BNST) under each image. For the scatterplots: Red = unpredictable, Blue = Threat, Green = Neutral, Teal = Predictable.

Figure 3.. BNST and amygdala responses to cues and image.

The BNST and amygdala show a significant dissociation by cue type (region × cue type interaction, p = .02), which represents a significant region effect for the unpredictable cue. In contrast, there are no significant regional differences by image type (predictable vs unpredictable) or valence (threat vs neutral).

Figure 4.. Social anxiety moderates BNST vs amygdala responses to unpredictable threat images.

Left: Social anxiety scores are positively correlated with a difference between the BNST and amygdala responses to unpredictable (threat – neutral) images. Right: Social anxiety scores were binned into tertiles to illustrate the shift from amygdala > BNST to BNST > amygdala responses to unpredictable threat.