Resting state connectivity of the bed nucleus of the stria terminalis at ultra‐high field

Abstract

The bed nucleus of the stria terminalis (BNST), a portion of the ‘extended amygdala’, is implicated in the pathophysiology of anxiety and addiction disorders. Its small size and connection to other small regions prevents standard imaging techniques from easily capturing it and its connectivity with confidence. Seed-based resting state functional connectivity is an established method for mapping functional connections across the brain from a region of interest. We therefore mapped the BNST resting state network with high spatial resolution using 7 Tesla fMRI, demonstrating the in vivo reproduction of many human BNST connections previously described only in animal research. We identify strong BNST functional connectivity in amygdala, hippocampus and thalamic subregions, caudate, periaqueductal gray, hypothalamus and cortical areas such as the medial PFC and precuneus. This work, which demonstrates the power of ultra-high field for mapping functional connections in the human, is an important step towards elucidating cortical and subcortical regions and subregions of the BNST network.

Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies

“…Classic studies, mostly performed in rodents, define the EAc in part, by: 1) ‘symmetric’ organization of the BSTL and Ce subdivisions in terms of neuropeptide and transmitter markers (Alheid and Heimer 1988; McDonald 2003); 2) robust connections among the BSTL, Ce and SLEAc (Grove 1988a; Grove 1988b); and 3) many common afferent and efferent projections (Gray and Magnuson 1987; Gray and Magnuson 1992; McDonald et al 1999; Moga et al 1990; Nagy and Pare 2008; Reynolds and Zahm 2005; Rinaman et al 2000; Wallace et al 1992). These anatomical features, together with functional imaging studies (Birn et al 2014; Oler et al 2012; Torrisi et al 2015) suggest that the EAc is both a structural and functional unit. However, few anatomic data exist to validate these concepts in primates.…”

Contributions of the Central Extended Amygdala to Fear and Anxiety

“…More recent tracing and diffusion imaging studies in monkeys have not only confirmed that the Ce and BSTL are structurally interconnected via these two direct pathways (primarily Ce ¡ BSTL) but have also identified a novel indirect pathway in the SLEA (Ce 7 SLEA 7 BSTL) (deCampo and Fudge, 2013;Oler et al, 2016b). In both monkeys and humans, the Ce and BST also show persistently high levels of physiological coupling Avery et al, 2014;Birn et al, 2014;Torrisi et al, 2015;Oler et al, 2016b), suggesting that they represent an evolutionarily conserved functional circuit.…”

“…1, 2). In human fMRI studies, many of these downstream regions (e.g., hypothalamus, periaqueductal gray) also show robust functional connectivity with the BST (Torrisi et al, 2015).…”

“…Although imaging studies reporting amygdala activation number in the thousands, far fewer studies report activations in the BST. This discrepancy partially reflects the fact that automated tools for assigning anatomical labels to activation clusters do not yet include the BST, although probabilistic anatomical masks have recently become available (Avery et al, 2014;Torrisi et al, 2015). As a consequence, investigators without a strong background in neuroanatomy may not realize that a cluster encompasses the BST or may mis-assign it to neighboring regions in the basal ganglia.…”

The Neurobiology of Dispositional Negativity and Attentional Biases to Threat: Implications for Understanding Anxiety Disorders in Adults and Youth

“…Although investigators need to be cautious when assigning specific labels (e.g., BL, BST, Ce) to activation clusters in imaging studies, we encourage them to describe the relative position of activation peaks (e.g., dorsal-posterior amygdala) and interpret their results on the basis of the most likely subcomponent of the extended amygdala (e.g., ‘in the region of the BST’). The use of high-field MRI or specialized analytic approaches (e.g., using spatially unsmoothed data) may also prove useful (Avery et al, 2014; Sladky et al, 2013; Torrisi et al, 2015; van der Zwaag, Da Costa, Zurcher, Adams, & Hadjikhani, 2012). …”