Bed nucleus of the stria terminalis and amygdala responses to unpredictable threat in children

Dev Psychobiol. 2021 Dec;63(8):e22206. doi: 10.1002/dev.22206.


Substantial evidence from studies in humans suggests the amygdala is pivotal for anxiety. Findings from animal models and translational studies suggests the bed nucleus of the stria terminalis (BNST) is also critical for anxiety and the anticipation of unpredictable threat in adults. However, it remains unknown whether the BNST is involved in unpredictable threat anticipation in children. Forty-two 8-10-year-olds completed resting-state functional magnetic resonance imaging (fMRI) scans and an unpredictable threat fMRI task in which they were trained to associate cues with images. Intrinsic connectivity analyses were performed to establish functional BNST and amygdala networks. BNST and amygdala activation to cues and images was tested. Significant findings were followed by task-based functional connectivity analyses. Children showed evidence for BNST and amygdala intrinsic connectivity that was similar to previous patterns observed in adults. In response to unpredictable cues relative to neutral face cues, children had a significant amygdala response but no response in the BNST. The amygdala, but not the BNST, also showed a significantly greater response to fear face images relative to neutral images. Thus, unpredictable threat activated the amygdala, but not BNST, in children. This finding is contrary to studies showing robust BNST activation to unpredictable threat in adults and may suggest that the BNST's role in threat processing emerges later in development.

Keywords: anxiety; childhood; extended amygdala; fear; uncertainty.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / diagnostic imaging
  • Animals
  • Anticipation, Psychological / physiology
  • Anxiety Disorders
  • Fear / physiology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Septal Nuclei* / diagnostic imaging
  • Septal Nuclei* / physiology