Fear and Anxiety: Possible Roles of the Amygdala and Bed Nucleus of the Stria Terminalis

1998 ◽  
Vol 12 (3) ◽  
pp. 277-305 ◽  
Author(s):  
Michael Davis Young ◽  
Lim Lee
Keyword(s):  
Stria Terminalis ◽  
Bed Nucleus ◽  
Fear And Anxiety

scholarly journals Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex

1997 ◽  
Vol 352 (1362) ◽  
pp. 1675-1687 ◽  
Author(s):  
◽  
Michael Davis ◽  
David L. Walker ◽  
Younglim Lee
Keyword(s):  
Excitatory Amino Acid ◽  
Conditioned Fear ◽  
Acoustic Startle ◽  
Acoustic Startle Reflex ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Amino Acid Receptors ◽  
Sensory Modalities ◽  
Behavioural Tests ◽  
Fear And Anxiety

Neural stimuli associated with traumatic events can readily become conditioned so as to reinstate the memory of the original trauma. These conditioned fear responses can last a lifetime and may be especially resistant to extinction. A large amount of data from many different laboratories indicate that the amygdala plays a crucial role in conditioned fear. The amygdala receives information from all sensory modalities and projects to a variety of hypothalamic and brainstem target areas known to be critically involved in specific signs that are used to define fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviours that mimic natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear and local infusion of drugs into the amygdala have anxiolytic effects in several behavioural tests. Excitatory amino acid receptors in the amygdala are critical for the acquisition, expression and extinction of conditioned fear.

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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Travis D Goode ◽  
Reed L Ressler ◽  
Gillian M Acca ◽  
Olivia W Miles ◽  
Stephen Maren
Keyword(s):  
Conditioned Fear ◽  
Stria Terminalis ◽  
Conditioned Stimuli ◽  
Variable Intensity ◽  
Reversible Inactivation ◽  
Bed Nucleus ◽  
Defensive Behaviors ◽  
The Us ◽  
Specific Factors ◽  
Fear And Anxiety

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.

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

2018 ◽  
Author(s):  
Travis D. Goode ◽  
Reed L. Ressler ◽  
Gillian M. Acca ◽  
Olivia W. Miles ◽  
Stephen Maren
Keyword(s):  
Conditioned Fear ◽  
Stria Terminalis ◽  
Variable Intensity ◽  
Reversible Inactivation ◽  
Bed Nucleus ◽  
Defensive Behaviors ◽  
The Us ◽  
Specific Factors ◽  
Fear And Anxiety ◽  
Pathological Anxiety

ABSTRACTThe 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.IMPACT STATEMENTThe bed nucleus of the stria terminalis (BNST) is required for the expression of defensive behavior to unpredictable threats, a function that may be central to pathological anxiety.

scholarly journals Intrinsic functional connectivity of the central extended amygdala

2017 ◽  
Author(s):  
Rachael M. Tillman ◽  
Melissa D. Stockbridge ◽  
Brendon M. Nacewicz ◽  
Salvatore Torrisi ◽  
Andrew S. Fox ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
High Precision ◽  
Community Dwelling ◽  
Central Nucleus ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Extended Amygdala ◽  
Intrinsic Functional Connectivity ◽  
Multiband Imaging ◽  
Fear And Anxiety

ABSTRACTThe central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a key role in orchestrating states of fear and anxiety and is implicated in the development and maintenance of anxiety disorders, depression, and substance abuse. Although it is widely thought that these disorders reflect the coordinated actions of large-scale functional circuits in the brain, the architecture of the EAc functional network, and the degree to which the BST and the Ce show distinct patterns of intrinsic functional connectivity, remains incompletely understood. Here, we leveraged a combination of approaches to trace the connectivity of the BST and the Ce in 130 psychiatrically healthy, racially diverse, community-dwelling adults with enhanced power and precision. Multiband imaging, high-precision data registration techniques, and spatially unsmoothed data were used to maximize anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala (‘substantia innominata’), the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed significant coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed significantly stronger connectivity with prefrontal territories—including the vmPFC, anterior MCC and pregenual anterior cingulate cortex—as well as the thalamus, striatum, and the periaqueductal gray. The only regions showing stronger functional connectivity with the Ce were located in the anterior hippocampus and dorsal amygdala. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and highlight the value of several new approaches to image registration which may be particularly useful for researchers working with ‘de-identified’ neuroimaging data.GRAPHICAL ABSTRACTIntrinsic functional connectivity of bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce) in 130 psychiatrically healthy adults.HIGHLIGHTSBST and Ce implicated in normal and pathological fear and anxietyTraced the intrinsic functional connectivity of the BST and the Ce in 130 adultsMultiband imaging, high-precision registration, unsmoothed data, newly developed seedsBST and Ce show robust coupling with one another, hippocampus, insula, MCC, and vmPFCBST shows stronger coupling with prefrontal/cingulate territories and brainstem/PAG

Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder

2017 ◽  
Vol 47 (15) ◽  
pp. 2675-2688 ◽  
Author(s):  
L. Brinkmann ◽  
C. Buff ◽  
K. Feldker ◽  
S. V. Tupak ◽  
M. P. I. Becker ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Panic Disorder ◽  
Brain Regions ◽  
Panic Attacks ◽  
Anterior Cingulate ◽  
Stria Terminalis ◽  
Analysis Model ◽  
Bed Nucleus ◽  
Brain Responses ◽  
Fear And Anxiety

BackgroundPanic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD.MethodsUsing functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations.ResultsPD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks.ConclusionsWe demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

scholarly journals Social Isolation, Loneliness and Generalized Anxiety: Implications and Associations during the COVID-19 Quarantine

2021 ◽  
Vol 11 (12) ◽  
pp. 1620
Author(s):  
Linas Wilkialis ◽  
Nelson B. Rodrigues ◽  
Danielle S. Cha ◽  
Ashley Siegel ◽  
Amna Majeed ◽  
...  
Keyword(s):  
Social Isolation ◽  
Sedentary Lifestyle ◽  
Well Being ◽  
Generalized Anxiety ◽  
Stria Terminalis ◽  
Health Issues ◽  
Bed Nucleus ◽  
Anxiety Response ◽  
Anxious State ◽  
Fear And Anxiety

The COVID-19 pandemic has resulted in a predominantly global quarantine response that has been associated with social isolation, loneliness, and anxiety. The foregoing experiences have been amply documented to have profound impacts on health, morbidity, and mortality. This narrative review uses the extant neurobiological and theoretical literature to explore the association between social isolation, loneliness, and anxiety in the context of quarantine during the COVID-19 pandemic. Emerging evidence suggests that distinct health issues (e.g., a sedentary lifestyle, a diminished overall sense of well-being) are associated with social isolation and loneliness. The health implications of social isolation and loneliness during quarantine have a heterogenous and comorbid nature and, as a result, form a link to anxiety. The limbic system plays a role in fear and anxiety response; the bed nucleus of the stria terminalis, amygdala, HPA axis, hippocampus, prefrontal cortex, insula, and locus coeruleus have an impact in a prolonged anxious state. In the conclusion, possible solutions are considered and remarks are made on future areas of exploration.

scholarly journals The translational neural circuitry of anxiety

2019 ◽  
pp. jnnp-2019-321400 ◽  
Author(s):  
Oliver J Robinson ◽  
Alexandra C Pike ◽  
Brian Cornwell ◽  
Christian Grillon
Keyword(s):  
Treatment Outcomes ◽  
Neural Circuitry ◽  
Experimental Models ◽  
Future Research ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Subcortical Regions ◽  
Cortical Regions ◽  
Fear And Anxiety ◽  
Human Neuroimaging

Anxiety is an adaptive response that promotes harm avoidance, but at the same time excessive anxiety constitutes the most common psychiatric complaint. Moreover, current treatments for anxiety—both psychological and pharmacological—hover at around 50% recovery rates. Improving treatment outcomes is nevertheless difficult, in part because contemporary interventions were developed without an understanding of the underlying neurobiological mechanisms that they modulate. Recent advances in experimental models of anxiety in humans, such as threat of unpredictable shock, have, however, enabled us to start translating the wealth of mechanistic animal work on defensive behaviour into humans. In this article, we discuss the distinction between fear and anxiety, before reviewing translational research on the neural circuitry of anxiety in animal models and how it relates to human neuroimaging studies across both healthy and clinical populations. We highlight the roles of subcortical regions (and their subunits) such as the bed nucleus of the stria terminalis, the amgydala, and the hippocampus, as well as their connectivity to cortical regions such as dorsal medial and lateral prefrontal/cingulate cortex and insula in maintaining anxiety responding. We discuss how this circuitry might be modulated by current treatments before finally highlighting areas for future research that might ultimately improve treatment outcomes for this common and debilitating transdiagnostic symptom.

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