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Updated: Jan 26, 2026

Social Isolation Model: A Noninvasive Rodent Model of Stress and Anxiety
Published on: November 11, 2022
Social anxiety is associated with BNST response to unpredictability
Jacqueline A Clauss1, Suzanne N Avery2, Margaret M Benningfield2
1Department of Psychiatry, Massachusetts General and McLean Hospitals, Harvard Medical School, Boston, Massachusetts.
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.
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Anxiety: Overview
Individuals with anxiety often experience a range of physical and emotional symptoms, including sweating, trembling, tachycardia, and disturbances in sleep patterns. These symptoms vary in intensity and frequency but are generally disruptive and distressing.

