Bed Nucleus of the Stria Terminalis

Anatomy

• A group of nuclei around the anterior commissure, ventral to the lateral ventricle and lateral to the septum.
• Connected to the amygdala by the stria terminalis: this thin fiber bundle follows the C-shape of the caudate nucleus over the thalamus to reach the amygdala (a thin arc in the model).
• Together with the central amygdala and the accumbens shell it is called the “extended amygdala”.
• It has sexually dimorphic subnuclei.

Functions

• Sustained anxiety in response to uncertain, distant or unpredictable threats; the counterpart of the amygdala’s phasic fear response (Davis et al., 2010). In humans the BNST continuously tracks changes in threat level; in highly anxious individuals this tracking takes the form of hypervigilance (Somerville et al., 2010; 50 adults). B
• Regulation of the HPA axis (projection to the paraventricular nucleus).
• Maintenance of autonomic responses.
• Social, sexual and maternal behaviors; a bridge between the stress and reward systems.

Connections and chemistry

• Amygdala (stria terminalis)
• Hypothalamus PVN (HPA axis)
• PAG and brainstem autonomic nuclei
• Nucleus accumbens shell
• CRF, NPY, noradrenaline, oxytocin/vasopressin

Development

Developmental course through childhood and adolescence.

• Anxious temperament is partly heritable: in 592 young rhesus monkeys, the heritable risk was carried not by brain structure but by the metabolism of a prefrontal–limbic–midbrain circuit (Fox et al., 2015). A later study linked the metabolism of the central extended amygdala (central nucleus and BNST) to temperament. A model for the biology of behaviorally inhibited children. B
• In animal models, early-life stress has lasting effects on the CRF system in the BNST; pediatric human data are limited.

Clinical

• Generalized anxiety disorder: intolerance of uncertainty and sustained anticipatory anxiety.
• PTSD: constant hypervigilance, sustained threat response.
• In substance use, withdrawal and stress-triggered relapse (CRF).

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• SSRIs and CBT are first line in generalized anxiety disorder; benzodiazepines short term.
• CRF1 receptor antagonists reduced BNST-mediated anxiety in animal models but failed in humans: pexacerfont did not separate from placebo in generalized anxiety disorder (Coric et al., 2010), and no CRF1 antagonist has completed phase III. An example of the limits of translation from animals to humans. B
• CBT components targeting intolerance of uncertainty correspond to the BNST’s function (monitoring uncertain threat).

Assessment

Neuropsychological tasks and measures that probe this region's function.

• NPU threat task (neutral, predictable, unpredictable threat — Grillon)
• fMRI during threat anticipation
• Startle reflex in sustained fear

Lesions and damage

Clinical findings expected with damage or dysfunction.

• In animal studies, BNST lesions reduce the sustained anxiety response without impairing phasic fear.

In the model

How this structure is defined in the 3D model, and the data source.

CIT168 extended amygdala label (threshold 0.35). The stria terminalis is an approximate arc drawn by hand.

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Somerville LH, Whalen PJ, Kelley WM. Human bed nucleus of the stria terminalis indexes hypervigilant threat monitoring. Biol Psychiatry 2010;68(5):416–424. Search PubMed
2. Fox AS et al. Intergenerational neural mediators of early-life anxious temperament. PNAS 2015;112(29):9118–9122. Search PubMed
3. Coric V et al. Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder. Depress Anxiety 2010;27(5):417–425. Search PubMed