hide
Free keywords:
-
Abstract:
Introduction:
The Bed Nucleus of the Stria Terminalis (BNST) is a basal forebrain structure that surrounds the anterior commissure near its decussation. Repeated investigation of its anatomy, connectivity, and function has provided a multitude of theories concerning its role as a central relay of the extended amygdala [1]. The BNST has been shown to be involved in processing threat and stress, especially if they are sustained and contextual [8], to regulate emotional and hormonal reactions by influencing the hypothalamo-pituitary-adrenal hormone axis [4], to be responsible for the affective aspect of withdrawal [7], and therefore to promote the emergence and upkeep of addictive behavior [3]. In the present study, we aimed at depicting its connectivity profile, for the first time in living humans, by using diffusion tensor imaging based probabilistic tractography.
Methods:
Diffusion weighted imaging (DWI) data (30 directions; b-value 1000 s/mm²; voxel size 2×2×2 mm³; 2 acquisitions) was acquired from 23 participants at 3T. The region of interest was defined according to anatomical data [9]; due to the proximity of the ventral BNST to other grey matter structures (accumbens nucleus, preoptic area, substantia innominata, etc.), the seed region was restricted to the supracommissural BNST. Anatomical data was segmented and normalized, and binary grey matter seed masks (see Fig. 1) were created using SPM8. DWI data was corrected for eddy currents and averaged across the two acquisitions. Probabilistic fiber tracking, accounting for crossing fibers in each voxel [2], was performed using FSL, starting 5000 times from each voxel of the seed mask; fiber tracking was not restricted by target or waypoint masks. Normalized binary connectivity maps (thresholded at 1 of the maximum value) of the individual subjects were added and fiber projections present in more than 25, 50 and 75 of the subjects were displayed using FSLView and 3DSlicer.
Results:
Three main fiber tracts were identified (Fig 2): 1) A posterior bundle, situated in a sulcus between the ventricular borders of the caudate nucleus and the thalamus along the ventrolateral margin of the anterior horn of the lateral ventricle (LV), taking a curve around the posterior edge of the thalamus, then running in the roof of the inferior horn of the LV to the lateral margin of the amygdala; this pathway corresponds to the stria terminalis. 2) A ventral bundle entering the substantia innominata, where it diverges to terminate (a) in the hypothalamus and (b) at the medial margin of the amygdala; the latter branch is consistent with descriptions of the ansa peduncularis. 3) A rostral pathway, running through the transition zone of caudate and accumbens nucleus (see Fig. 4), to the medial and orbital prefrontal cortex. The latter appears discontinuous when displaying only fiber tracts common to more than 50 of the subjects (see Fig. 3); this is due to inter-individual differences in the exact course of this bundle, as this connection was found in 19 and 13 subjects in the right and left hemisphere, respectively.
Conclusions:
Tracer studies of fiber pathways connected to the BNST require invasive procedures on the living brain and thus are restricted to animal research. Therefore, the BNST's connectivity profile has not been investigated in humans yet. BNST connections to amygdala, hypothalamus, and further structures of the basal forebrain, as seen in the present data, have been described in animals. Animal studies also revealed connections to the brainstem, which are thought to play a role in the BNST's involvement in monoaminergic systems; however, we could only find these pathways in a few subjects, probably due to limitations of probabilistic fiber tracking in regions with multiple fiber directions. The fiber tract to the OFC is of particular interest, as it has not yet been described in lower mammals, but is consistent with the results of fMRI studies in primates that suggest functional connectivity between the BNST and OFC [5].
