Effective connectivity between bed nucleus of the stria terminalis and amygdala: Reproducibility and relation to anxiety

Abstract

In a previous study, we investigated the resting‐state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and the laterobasal (LB), centromedial (CM), and superficial (SF) amygdala. We found strong negative EC from all amygdala nuclei to the BNST, while the BNST showed positive EC to the amygdala. However, the validity of these findings remains unclear, since a reproduction in different samples has not been done. Moreover, the association of EC with measures of anxiety offers deeper insight, due to the known role of the BNST and amygdala in fear and anxiety. Here, we aimed to reproduce our previous results in three additional samples. We used spectral Dynamic Causal Modeling to estimate the EC between the BNST, the LB, CM, and SF, and its association with two measures of self‐reported anxiety. Our results revealed consistency over samples with regard to the negative EC from the amygdala nuclei to the BNST, while the positive EC from BNST to the amygdala was also found, but weaker and more heterogenic. Moreover, we found the BNST‐BNST EC showing a positive and the CM‐BNST EC, showing a negative association with anxiety. Our study suggests a reproducible pattern of negative EC from the amygdala to the BNST along with weaker positive EC from the BNST to the amygdala. Moreover, less BNST self‐inhibition and more inhibitory influence from the CM to the BNST seems to be a pattern of EC that is related to higher anxiety.

Dynamic effective connectivity among large‐scale brain networks mediates risk of anxiety

“…Their findings indicated that both high‐level cognitive networks and low‐level perceptual networks could contribute to estimating anxiety behaviors by their static functional profiles. Static effective connectivity studies further revealed abnormal effective connectivity associated with the amygdala, supporting a dysregulation of core structures in the affect control network of anxiety (Hofmann & Straube, 2021 ; Liao, Qiu, et al, 2010 ; Qiao et al, 2017 ). However, even in the resting state, the functional brain networks show significant time variability and dynamic reconstruction (Zhang et al, 2016 ).…”

“…The changes in effective connectivity patterns in emotional regulation regions may reflect directional neural communications, which provide deeper insights into anxiety (Hofmann & Straube, 2021). It is well known that the brain is highly dynamic rather than static.…”

“…Different from functional connectivity analysis, effective connectivity is a widely used method to explore directional time‐lagged relationships in nerve conduction pathways. The changes in effective connectivity patterns in emotional regulation regions may reflect directional neural communications, which provide deeper insights into anxiety (Hofmann & Straube, 2021 ). It is well known that the brain is highly dynamic rather than static.…”

Mental Resilience and Coping With Stress: A Comprehensive, Multi-level Model of Cognitive Processing, Decision Making, and Behavior

“…Conversely, intense stress can hyperactivate the LC that is associated with anxiety (Borodovitsyna et al, 2018;Morris et al, 2020) due to limbic dysregulation (e.g., Herman et al, 2005). In particular, it is related to the functional connectivity between the bed nucleus of the stria terminalis (BNST) and amygdala (e.g., Clauss, 2019;Knight and Depue, 2019;Hofmann and Straube, 2021). The nuances are that the amygdala is involved in explicit threat processing (i.e., threat confrontation), whereas the BNST is involved in ambiguous threat processing (i.e., threat anticipation; Herrmann et al, 2016;Klumpers et al, 2017;Naaz et al, 2019; see also Fox et al, 2015;Fox and Shackman, 2019;Luyck et al, 2019).…”

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System

“…The stria terminalis connects the BNST to the amygdala by a C-shaped course (Kamali et al 2015 ; Dzafic et al 2019 ; Hofmann and Straube 2021 ). Direct projections were also detected from the occipital cortex to the BNST in the human brain (Catani et al 2003 ; Avery et al 2014 , Kamali et al 2020b ).…”