Three distinct fiber pathways of the bed nucleus of the stria terminalis to the amygdala and prefrontal cortex

Krüger, Oliver; Shiozawa, Thomas; Kreifelts, Benjamin; Scheffler, Klaus; Ethofer, Thomas

doi:10.1016/j.cortex.2015.02.007

Cited by 78 publications

(61 citation statements)

References 49 publications

(78 reference statements)

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“…Although the location of this connection is novel in humans, the limen insulae is comprised of agranular neurons homologous to the caudal agranular insula in rodents that shows strong reciprocal connections with the BNST (Ding et al, 2009;Reynolds and Zahm, 2005;Turner and Zimmer, 1984), suggesting that this is an evolutionarily conserved connection across species. A recent study replicated a similar structural connection between the BNST and temporal pole region in humans (Krüger et al, 2015). The post hoc analysis of the anterior and posterior insula, separately, revealed a significant connection with the anterior insula as well.…”

Section: Bnst Structural Connections In Humanssupporting

confidence: 65%

The Human BNST: Functional Role in Anxiety and Addiction

Avery

Clauss

Blackford

2015

Neuropsychopharmacol

268

206

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The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region-the bed nucleus of the stria terminalis (BNST)-in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stressrelated disorders and identify novel neural targets for treatment.

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Section: Bnst Structural Connections In Humanssupporting

confidence: 65%

The Human BNST: Functional Role in Anxiety and Addiction

Avery

Clauss

Blackford

2015

Neuropsychopharmacol

268

206

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“…For example, Pleil et al (2015) found an effect of chronic alcohol drinking on the BNST that was conserved between mice and monkeys. Importantly, recent neuroimaging studies have shown that the connectivity of the BNST in humans is in large part similar to that of rodents and non-human primates, with the addition of connections between the BNST and more rostral cortical areas such as the orbitofrontal cortex (Avery et al, 2014, Krüger et al, 2015. Functional imaging studies have shown that the BNST is hyperactive in patients with generalized anxiety disorder (Yassa et al, 2012) and in patients with specific-phobias (Straube et al, 2007), consistent with a role for the BNST in pathological anxiety in humans.…”

Section: Discussionmentioning

confidence: 85%

Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis

Daniel

Rainnie

2015

Neuropsychopharmacol

174

191

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The anterior bed nucleus of the stria terminalis (BNST) has been recognized as a critical structure in regulating trait anxiety, contextual fear memory, and appetitive behavior, and is known to be sensitive to stress manipulations. As one of the most complex structures in the central nervous system, the intrinsic circuitry of the BNST is largely unknown; however, recent technological developments have allowed researchers to begin to untangle the internal connections of the nucleus. This research has revealed the possibility of two opposing circuits, one anxiolytic and one anxiogenic, within the BNST, the relative strength of which determines the behavioral outcome. The balance of these pathways is critical in maintaining a normal physiological and behavioral state; however, stress and drugs of abuse can differentially affect the opposing circuitry within the nucleus to shift the balance to a pathological state. In this review, we will examine how stress interacts with the neuromodulators, corticotropin-releasing factor, norepinephrine, dopamine, and serotonin to affect the circuitry of the BNST as well as how synaptic plasticity in the BNST is modulated by stress, resulting in long-lasting changes in the circuit and behavioral state.

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“…The BNST plays an important role during sustained threat states (Davis and Shi, 1999; Walker et al, 2003), and has strong anatomical connections to the accumbens (Alheid et al, 1998; Brog et al, 1993; Delfs et al, 1998; Dong et al, 2001; Dong and Swanson, 2004; Georges and Aston-Jones, 2001; Krüger et al, 2015). Because the spatial resolution employed in our study was relatively coarse (3 mm isotropic voxels), the signals arising from accumbens and the BNST cannot be dissociated and we cannot determine whether or not the functional connectivity changes we have identified are specific to either particular brain structure.…”

Section: Discussionmentioning

confidence: 99%

Discovering networks altered by potential threat (“anxiety”) using quadratic discriminant analysis

McMenamin

Pessoa

2015

NeuroImage

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Researchers have only recently begun using functional neuroimaging to explore the human response to periods of sustained anxious anticipation, namely potential threat. Here, we investigated brain responses acquired with functional MRI during an instructed threat of shock paradigm used to create sustained periods of aversive anticipation. In this re-analysis of previously published data, we employed Quadratic Discriminant Analysis to classify the multivariate pattern of whole-brain functional connectivity and to identify connectivity changes during periods of potential threat. Our method identifies clusters with altered connectivity on a voxelwise basis, thus eschewing the need to define regions a priori. Classifier generalization was evaluated by testing on data from participants not used during training. Robust classification between threat and safe contexts was possible, and inspection of “diagnostic features” revealed altered functional connectivity involving the intraparietal sulcus, task-negative regions, striatum, and anterior cingulate cortex. We anticipate that the proposed method will prove useful to experimenters wishing to identify large-scale functional networks that distinguish between experimental conditions or groups.

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Three distinct fiber pathways of the bed nucleus of the stria terminalis to the amygdala and prefrontal cortex

Cited by 78 publications

References 49 publications

The Human BNST: Functional Role in Anxiety and Addiction

The Human BNST: Functional Role in Anxiety and Addiction

Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis

Discovering networks altered by potential threat (“anxiety”) using quadratic discriminant analysis

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