Functional MRI of the amygdala and bed nucleus of the stria terminalis during conditions of uncertainty in generalized anxiety disorder

Abstract

Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by constant worry or anxiety over every day life activities and events. The neurobiology of the disorder is thought to involve a wide cortical and subcortical network that includes but is not limited to the amygdala and the bed nucleus of the stria terminalis (BNST). These two regions have been hypothesized to play different roles in stress and anxiety; the amygdala is thought to regulate responses to brief emotional stimuli while the BNST is thought to be involved in more chronic regulation of sustained anxiety. In this study, we exposed medication-free GAD patients as well as non-anxious controls to a gambling game where one of the conditions involved non-contingent monetary loss. This condition of high uncertainty was intended to elicit a stressful response and sustained anxiety. Functional MRI scans were collected simultaneously to investigate BOLD activity in the amygdala and BNST during performance of this task. Compared to controls, we found that GAD patients demonstrated decreased activity in the amygdala and increased activity in the BNST. Skin conductance measures showed a consistent early versus late effect within block where GAD patients demonstrated higher arousal than controls late in the task blocks. Based on these results, we hypothesize that GAD patients disengage the amygdala and its response to acute stress earlier than non-anxious controls making way for the BNST to maintain a more sustained response. Future studies are needed to investigate the temporal dynamics of activation and deactivation in these regions.

Activation of Hypocretin-1/Orexin-A Neurons Projecting to the Bed Nucleus of the Stria Terminalis and Paraventricular Nucleus Is Critical for Reinstatement of Alcohol Seeking by Neuropeptide S

“…The third and most intriguing conclusion is that facilitation of cue-induced reinstatement by NPS appears to be mediated by Hcrt-1/Ox-A neurons innervating areas classically linked to stress (PVN and BNST) rather than to incentive motivation and reinforcement (VTA and LC). The BNST is, in fact, well known for mediating various affective and emotional aspects of stress (43,50), whereas the PVN is primarily involved in the regulation of hormonal responses to stress (45). Hence, considering that environmental conditioning factors and stress play additive roles in relapse in drug addicts (1,3), it is tempting to speculate that concerted regulation of NPS and Hcrt-1/Ox-A transmission may be responsible for the interaction between these two main relapse factors.…”

CGRP antagonist infused into the bed nucleus of the stria terminalis impairs the acquisition and expression of context but not discretely cued fear

“…There is now substantial evidence of BNST activation during evoked anxiety in humans (i.e., from imaging studies [Hasler et al 2007;Straube et al 2007;Somerville et al 2010Somerville et al , 2013Alvarez et al 2011;Yassa et al 2012]), and compelling evidence that electrical stimulation of a brain area lying at the junction of the anterior capsule, anterior commissure, and posterior ventral striatum-an area which corresponds very closely to the area targeted by our cannula-markedly reduces anxiety and depression in patients with otherwise intractable obsessive-compulsive disorder (Greenberg et al 2010). That pharmacological modulation of BNST might also prove therapeutic is an exciting prospect.…”

The Human BNST: Functional Role in Anxiety and Addiction

“…Spider phobics showed greater BNST activity during anticipation of spider images relative to the mushroom image. In a group of generalized anxiety disorder (GAD) patients, however, Yassa et al (2012) failed to show a statistically significant difference in BNST response to high vs low stress conditions relative to controls, although GAD patients showed marginally greater BNST activity (P = 0.10). Task differences between these two studies may be key-Yassa et al (2012) manipulated stress using a monetary loss task that may promote a very different brain response than threats such as shock or spiders.…”