Extended-amygdala intrinsic functional connectivity networks: A population study

Pre-clinical and human neuroimaging research implicates the extended-amygdala (ExtA) (including the bed nucleus of the stria terminalis [BST] and central nucleus of the amygdala [CeA]) in networks mediating negative emotional states associated with stress and substance-use behaviours. The extent to which individual ExtA structures form a functionally integrated unit is controversial. We utilised a large sample (n > 1,000 healthy young adult humans) to compare the intrinsic functional connectivity networks (ICNs) of the BST and CeA using task-free functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. We assessed whether inter-individual differences within these ICNs were related to two principal components representing negative disposition and alcohol use. Building on recent primate evidence, we tested whether within BST-CeA intrinsic functional connectivity (iFC) was heritable and further examined co-heritability with our principal components. We demonstrate the BST and CeA to have discrete, but largely overlapping ICNs similar to previous findings. We found no evidence that within BST-CeA iFC was heritable; however, post hoc analyses found significant BST iFC heritability with the broader superficial and centromedial amygdala regions. There were no significant correlations or co-heritability associations with our principal components either across the ICNs or for specific BST-Amygdala iFC. Possible differences in phenotype associations across task-free, task-based, and clinical fMRI are discussed, along with suggestions for more causal investigative paradigms that make use of the now well-established ExtA ICNs.

Automated summary

Pre-clinical and human neuroimaging research indicates that the extended-amygdala (ExtA) plays a role in regulating negative emotional states and substance-use behaviors. A study with a large sample of healthy young adults found that the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (CeA) have overlapping intrinsic functional connectivity networks (ICNs), but no evidence of heritability within the BST-CeA connection was found. Additionally, there were no significant correlations or co-heritability associations with negative disposition and alcohol use across the ICNs or for specific BST-amygdala intrinsic functional connectivity.