Can electrical stimulation of the human bed nucleus of the stria terminalis reduce contextual anxiety? An unanswered question

Citation: Luyck K and Luyten L (2015) Can electrical stimulation of the human bed nucleus of the stria terminalis reduce contextual anxiety? An unanswered question. In their paper, Baas et al. (2014), take the rather unique opportunity to conduct a human fear conditioning experiment in subjects with stimulation electrodes in the nucleus accumbens and internal capsule. Here, we argue that it might be premature to draw the strong conclusion that deep brain stimulation (DBS) does not impact contextual anxiety. We will elaborate on two aspects of the study that were not thoroughly discussed in the original paper, but that might help explain why no effects were found. Firstly, we will focus on the neuroanatomy and, secondly, on the behavioral procedure. The authors did not mention the precise location of the stimulation contact, but previous work from the same group allowed us to piece together a more detailed view of the actual stimulation site. While the distal lead tip was implanted in the nucleus accumbens, the active contact was located in the ventral part of the anterior limb of the internal capsule (ALIC) (van den Munckhof et al., 2013). The authors stated that these active contacts overlap with the bed nucleus of the stria termi-nalis (BST), or are at least in close proximity to this nucleus. Moreover, they hypothesized that they would be able to stimulate the BST and/or its connections and thereby affect contextual anxiety in their patients. However, a closer examination of the neuroanatomy shows that it is unlikely that the authors could sufficiently influence the BST (Figure 1). With monopolar stimulation, it can be estimated that the stimulated volume extends 4.4 mm (the average stimulation amplitude used in these patients was 4.4 V) from the center of the electrode (Mädler and Coenen, 2012). The anterior tip of the BST is located 3.4 mm from the active contact, in theory allowing the researchers to stimulate the most anterior millimeter of the BST (which has a total anterior-posterior extent of about 6.5 mm). Importantly, it appears that this most anterior BST portion is not the essential location with regard to (unpredictable) threat. Rather, it seems that more posterior parts of the BST, further away from the contact and outside of the stimulated volume, are involved in human threat paradigms (Figure 1) (Straube et al., 2007; Somerville et al., 2010; Alvarez et al., 2011). In line with this, we previously found …