Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders.

ABSTRACT: The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases. Most research on stress and psychiatric diseases has focused on the amygdala, which regulates immediate responses to fear. However, the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic-pituitary-adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities. In this review, we will look in-depth at the anatomy and projections of the BNST, and provide an overview of the current literature on the relevance of BNST dysregulation in psychiatric diseases.

SUBMITTER: Lebow MA

PROVIDER: S-EPMC4804181 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Intrinsic functional connectivity of the central nucleus of the amygdala and bed nucleus of the stria terminalis.

Project description:The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST.

| S-EPMC5630489 | biostudies-literature

Threat bias and resting state functional connectivity of the amygdala and bed nucleus stria terminalis.

Project description:BACKGROUND:Previous research has distinguished the activations of the amygdala and bed nucleus of stria terminalis (BNST) during threat-related contingencies. However, how intrinsic connectivities of the amygdala and BNST relate to threat bias remains unclear. Here, we investigated how resting state functional connectivity (rsFC) of the amygdala and BNST in healthy controls (HC) and patients with anxiety-related disorders (PAD) associate with threat bias in a dot-probe task. METHODS:Imaging and behavioral data of 30 PAD and 83 HC were obtained from the Nathan Kline Institute - Rockland sample and processed according to published routines. All imaging results were evaluated at voxel p < 0.001 and cluster p < 0.05, FWE corrected in SPM. RESULTS:PAD and HC did not show differences in whole brain rsFC with either the amygdala or BNST. In linear regressions threat bias was positively correlated with amygdala-thalamus/anterior cingulate cortex (ACC) rsFC in HC but not PAD, and with BNST-caudate rsFC in PAD but not HC. Slope tests confirmed group differences in the correlations between threat bias and amygdala-thalamus/ACC as well as BNST-caudate rsFC. LIMITATIONS:As only half of the patients included were diagnosed with comorbid anxiety, the current findings need to be considered with the clinical heterogeneity and require replication in populations specifically with anxiety disorders. CONCLUSIONS:Together, these results suggest amygdala and BNST connectivities as new neural markers of anxiety disorders. Whereas amygdala-thalamus/ACC rsFC support adaptive regulation of threat response in the HC, BNST-caudate rsFC may reflect maladaptive neural processes that are dominated by anticipatory anxiety.

| S-EPMC7010552 | biostudies-literature

Effective connectivity between bed nucleus of the stria terminalis and amygdala: Reproducibility and relation to anxiety.

Project description:In a previous study, we investigated the resting-state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and the laterobasal (LB), centromedial (CM), and superficial (SF) amygdala. We found strong negative EC from all amygdala nuclei to the BNST, while the BNST showed positive EC to the amygdala. However, the validity of these findings remains unclear, since a reproduction in different samples has not been done. Moreover, the association of EC with measures of anxiety offers deeper insight, due to the known role of the BNST and amygdala in fear and anxiety. Here, we aimed to reproduce our previous results in three additional samples. We used spectral Dynamic Causal Modeling to estimate the EC between the BNST, the LB, CM, and SF, and its association with two measures of self-reported anxiety. Our results revealed consistency over samples with regard to the negative EC from the amygdala nuclei to the BNST, while the positive EC from BNST to the amygdala was also found, but weaker and more heterogenic. Moreover, we found the BNST-BNST EC showing a positive and the CM-BNST EC, showing a negative association with anxiety. Our study suggests a reproducible pattern of negative EC from the amygdala to the BNST along with weaker positive EC from the BNST to the amygdala. Moreover, less BNST self-inhibition and more inhibitory influence from the CM to the BNST seems to be a pattern of EC that is related to higher anxiety.

| S-EPMC7814768 | biostudies-literature

Resting-state fMRI effective connectivity between the bed nucleus of the stria terminalis and amygdala nuclei.

Project description:The bed nucleus of the stria terminalis (BNST) and the laterobasal nucleus (LB), centromedial nucleus (CM), and superficial nucleus (SF) of the amygdala form an interconnected dynamical system, whose combined activity mediates a variety of behavioral and autonomic responses in reaction to homeostatic challenges. Although previous research provided deeper insight into the structural and functional connections between these nuclei, studies investigating their resting-state functional magnetic resonance imaging (fMRI) connectivity were solely based on undirected connectivity measures. Here, we used high-quality data of 391 subjects from the Human Connectome Project to estimate the effective connectivity (EC) between the BNST, the LB, CM, and SF through spectral dynamic causal modeling, the relation of the EC estimates with age and sex as well as their stability over time. Our results reveal a time-stable asymmetric EC structure with positive EC between all amygdala nuclei, which strongly inhibited the BNST while the BNST exerted positive influence onto all amygdala nuclei. Simulation of the impulse response of the estimated system showed that this EC structure shapes partially antagonistic (out of phase) activity flow between the BNST and amygdala nuclei. Moreover, the BNST-LB and BNST-CM EC parameters were less negative in males. In conclusion, our data points toward partially separated information processing between BNST and amygdala nuclei in the resting-state.

| S-EPMC6865382 | biostudies-literature

Human bed nucleus of the stria terminalis indexes hypervigilant threat monitoring.

Project description:BackgroundThough a key symptom underlying many anxiety disorders is hypervigilant threat monitoring, its biological bases in humans remain poorly understood. Animal models suggest that anxious processes such as hypervigilant threat monitoring are distinct from cued fear-like responses and mediated by the bed nucleus of the stria terminalis (BNST). Here, we applied psychophysiological and neuroimaging methodologies sensitive to sustained arousal-based responses to test the role of the human BNST in mediating environmental threat monitoring, a potential experimental model for sustained anxiety symptoms.MethodsHealthy participants (n = 50) with varying trait anxiety performed an environmental threat-monitoring task during functional magnetic resonance imaging where a stimulus line continuously fluctuated in height, providing information relevant to subsequent risk for electric shocks. Skin conductance was collected in a separate cohort (n = 47) to validate task-evoked modulation of physiological arousal.ResultsA forebrain region consistent with the BNST showed greater overall recruitment and exaggerated tracking of threat proximity in individuals with greater anxiety. The insular cortex tracked threat proximity across all participants, showed exaggerated threat proximity responding with greater anxiety, and showed enhanced recruitment when threat proximity was ostensibly controllable.ConclusionsActivity in the BNST and insula continuously monitored changes in environmental threat level and also subserved hypervigilant threat-monitoring processes in more highly trait anxious individuals. These findings bridge human and animal research informing the role of the BNST in anxious-related processes. In addition, these findings suggest that continuous functional magnetic resonance imaging paradigms offer promise in further elucidating the neural circuitries supporting sustained anticipatory features of anxiety.

| S-EPMC2921460 | biostudies-literature

Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder.

Project description:Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD.

| S-EPMC5714227 | biostudies-literature

Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals.

Project description:The bed nucleus of the stria terminalis (BNST) has been implicated in conditioned fear and anxiety, but the specific factors that engage the BNST in defensive behaviors are unclear. Here we examined whether the BNST mediates freezing to conditioned stimuli (CSs) that poorly predict the onset of aversive unconditioned stimuli (USs) in rats. Reversible inactivation of the BNST selectively reduced freezing to CSs that poorly signaled US onset (e.g., a backward CS that followed the US), but did not eliminate freezing to forward CSs even when they predicted USs of variable intensity. Additionally, backward (but not forward) CSs selectively increased Fos in the ventral BNST and in BNST-projecting neurons in the infralimbic region of the medial prefrontal cortex (mPFC), but not in the hippocampus or amygdala. These data reveal that BNST circuits regulate fear to unpredictable threats, which may be critical to the etiology and expression of anxiety.

| S-EPMC6456295 | biostudies-literature

Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior.

Project description:Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2 -/- ) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA ? BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.

| S-EPMC6233075 | biostudies-literature

Dissociation between amygdala and bed nucleus of the stria terminalis during threat anticipation in female post-traumatic stress disorder patients.

Project description:Feelings of uncontrollability and anxiety regarding possibly harmful events are key features of post-traumatic stress disorder (PTSD) symptomatology. Due to a lack of studies, the neural correlates of anticipatory anxiety in PTSD are still poorly understood. During functional magnetic resonance imaging, female PTSD patients with interpersonal violence trauma and healthy controls (HC) anticipated the temporally unpredictable presentation of aversive (human scream) or neutral sounds. Based on separate analysis models, we investigated phasic and sustained brain activations. PTSD patients reported increased anxiety during anticipation of aversive versus neutral sounds. Furthermore, we found both increased initial, phasic amygdala activation and increased sustained activation of the bed nucleus of the stria terminalis (BNST) during anticipation of aversive versus neutral sounds in PTSD patients in comparison to HC. PTSD patients as compared with HC also showed increased phasic responses in mid-cingulate cortex (MCC), posterior cingulate cortex (PCC), mid-insula and lateral prefrontal cortex (PFC) as well as increased sustained responses in MCC, PCC, anterior insula and lateral and medial PFC. Our results demonstrate a relationship between anticipatory anxiety in PTSD patients and hyperresponsiveness of brain regions that have previously been associated with PTSD symptomatology. Additionally, the dissociation between amygdala and BNST indicates distinct temporal and functional characteristics and suggests that phasic fear and sustained anxiety responses are enhanced during unpredictable anticipation of aversive stimuli in PTSD. Hum Brain Mapp 38:2190-2205, 2017. © 2017 Wiley Periodicals, Inc.

| S-EPMC6866898 | biostudies-literature

The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice.

Project description:Drug-associated stimuli are considered important factors in relapse to drug use. In the absence of drug, these cues can trigger drug craving and drive subsequent drug seeking. One structure that has been implicated in this process is the bed nucleus of the stria terminalis (BNST), a chief component of the extended amygdala. Previous studies have established a role for the BNST in cue-induced cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking of other abused drugs such as ethanol. In the present set of experiments, BNST involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using the conditioned place preference procedure (CPP). The BNST was inhibited during CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and activation of inhibitory designer receptors exclusively activated by designer drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of ethanol CPP was reduced significantly by each of these techniques. Notably, infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3 showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is involved in the modulation of cue-induced ethanol-seeking behavior.

| S-EPMC4668125 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data