Deep brain stimulation in the bed nucleus of the stria terminalis: A symptom provocation study in patients with obsessive-compulsive disorder.

BACKGROUND: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant obsessive-compulsive disorder (OCD), and several targets for electrode implantation and contact selection have been proposed, including the bed nucleus of the stria terminalis (BST). Selecting the active electrode contacts (patients typically have four to choose from in each hemisphere), and thus the main locus of stimulation, can be a taxing process. Here, we investigated whether contact selection based purely on their neuroanatomical position in the BST is a worthwhile approach. For the first time, we also compared the effects of uni- versus bilateral BST stimulation. METHODS: Nine OCD patients currently receiving DBS participated in a double-blind, randomized symptom provocation study to compare no versus BST stimulation. Primary outcomes were anxiety and mood ratings in response to disorder-relevant trigger images, as well as ratings of obsessions, compulsions, tendency to avoid and overall wellbeing. Furthermore, we asked whether patients preferred the electrode contacts in the BST over their regular stimulation contacts as a new treatment setting after the end of the task. RESULTS: We found no statistically significant group differences between the four conditions (no, left, right and bilateral BST stimulation). Exploratory analyses, as well as follow-up data, did indicate that (bilateral) bipolar stimulation in the BST was beneficial for some patients, particularly for those who had achieved unsatisfactory effects through the typical contact selection procedure. CONCLUSIONS: Despite its limitations, this study suggests that selection of stimulation contacts in the BST is a viable option for DBS in treatment-resistant OCD patients.

It takes two: Bilateral bed nuclei of the stria terminalis mediate the expression of contextual fear, but not of moderate cued fear.

A growing body of research supports a prominent role for the bed nucleus of the stria terminalis (BST) in the expression of adaptive and perhaps even pathological anxiety. The traditional premise that the BST is required for long-duration responses to threats, but not for fear responses to distinct, short-lived cues may, however, be oversimplified. A thorough evaluation of the involvement of the BST in cued and contextual fear is therefore warranted. In a series of preregistered experiments using male Wistar rats, we first addressed the involvement of the BST in cued fear. Following up on earlier work where we found that BST lesions disrupted auditory fear while the animals were in a rather high stress state, we here show that the BST is not required for the expression of more specific fear for the tone under less stressful conditions. In the second part, we corroborate that the same lesion method does attenuate contextual fear. Furthermore, despite prior indications for an asymmetric recruitment of the BST during the expression of anxiety, we found that bilateral lesioning of the BST is required for a significant attenuation of the expression of contextual fear. A functional BST in only one hemisphere resulted in increased variability in the behavioral outcome. We conclude that, in animals that acquired a fear memory with an intact brain, the bilateral BST mediates the expression of contextual fear, but not of unambiguous cued fear.

Electrolytic post-training lesions of the bed nucleus of the stria terminalis block startle potentiation in a cued fear conditioning procedure.

Existing neuroanatomical models argue that the bed nucleus of the stria terminalis (BST) principally mediates sustained, long-lasting fear or anxiety responses, but not shorter, phasic fear responses, although recent studies paint a more complex picture. In the current study, we evaluated the effect of post-training electrolytic BST lesions in a cued fear conditioning protocol with relatively short (10 s) tones. We hypothesized that the BST would not play a crucial role in the expression of fear upon re-exposure to the conditioned tones. Tone fear memory was primarily assessed through fear-potentiated startle. In addition, freezing measurements were obtained throughout the test sessions. In a series of three experiments, we explored the effects of BST lesions, taking into consideration contextual influences on cued fear expression (using (dis)similar training and test contexts) and temporal involvement of the BST in the consolidation of fear learning (lesion induction 3 or 27 h after fear conditioning). In all three experiments, we found that post-training electrolytic lesions of the BST significantly reduced fear-potentiated startle, implying a deficit in differentiation between tone and context. These results are surprising and challenge the general consensus on the lack of BST involvement in cued fear. We discuss several alternative explanations that may account for these unexpected findings.