The Bed Nucleus of the Stria Terminalis:Connections, genetics, & trait associations

This thesis examines the functional and structural connections of the Bed Nucleus of the Stria Terminalis (BNST). The principal motivation in doing so stems from the documented gap in our knowledge between the prolific pre-clinical animal BNST research, and that of human BNST research (Lebow & Chen, 2016). Understanding the human BNST may prove to be clinically important, as animal models often implicate this structure as being key in processes underlying the stress-response, disorders of negative affect, and in substance misuse- particularly related to alcohol (Herman et al., 2020; Maita et al., 2021). Therefore I further set out to test BNST connectivity relationships with related psychological phenotypes and examine any genetic associations. Chapter 1 provides an overview of the relevant BNST literature and a brief summary of the methods used in this thesis. In Chapter 2 I use the Human Connectome Project young human adults sample (n = ~1000) to map the intrinsic connectivity network of the BNST. In addition, I compare this network to that of the central nucleus of the amygdala, an area anatomically and functionally associated with the BNST (Alheid, 2009). Next, I test for associations across this network with self-report traits relating to dispositional negativity and alcohol use. Finally, I examine the heritability of specific BNST- amygdala sub-region functional connectivity, and co-heritability with the selfreport traits. In Chapter 3 I use the large UK biobank sample (n = ~ 19,000) to run a genome-wide association analysis, aiming to uncover specific common genetic variants that may be linked with BNST – amygdala sub-region functional connectivity. In Chapter 4, I focus on structural connectivity and use a mixture of macaque tracttracing analysis, and human and macaque diffusion MRI probabilistic tractography to examine the evidence for a connection between the subiculum and the BNST. As well, I test for associations between measures of white-matter microstructure and self-report dispositional negativity and alcohol-use phenotypes. Finally, in the Discussion, I bring together the findings of the research, noting their implications within the wider BNST literature and making several suggestions for improving similar analysis in future.