Explicit and Ambiguous Threat Processing: Functionally Dissociable Roles of the Amygdala and Bed Nucleus of the Stria Terminalis

2019 ◽  
Vol 31 (4) ◽  
pp. 543-559 ◽  
Author(s):  
Farah Naaz ◽  
Lindsay K. Knight ◽  
Brendan E. Depue

Highly influential models have proposed that responses to different types of threat are mediated by partially segregated neural systems, with the amygdala underlying phasic responses to explicit threat (fear) and the bed nucleus of the stria terminalis (BNST) mediating sustained responses to ambiguous threat (anxiety). However, newer models have suggested similar recruitment of both regions across a wide spectrum of threat. Therefore, to empirically test these models and further elucidate the activation profiles and connectivity patterns of the amygdala and the BNST during threat processing, 20 participants were scanned using high-resolution fMRI (1.5 mm3). Using fearful faces and human screams as aversive stimuli, two threat conditions were created: Explicit Threat in which threats were certain and predictable (fear) and Ambiguous Threat in which threats were uncertain and unpredictable (anxiety). Results indicated that, although the amygdala and the BNST both showed heightened engagement across both threat conditions, the amygdala showed preferential engagement during Explicit Threat and displayed functional connectivity with regions involved in stimulus processing and motor response. By contrast, the BNST preferentially responded during Ambiguous Threat and exhibited functional connectivity with prefrontal regions underlying interoception and rumination. Furthermore, correlations with questionnaires measuring trait anxiety, worry, and rumination suggested that individual differences in affective style play a modulatory role in regional recruitment and network connectivity during threat processing.

NeuroImage ◽  
2018 ◽  
Vol 166 ◽  
pp. 110-116 ◽  
Author(s):  
Leonie Brinkmann ◽  
Christine Buff ◽  
Katharina Feldker ◽  
Paula Neumeister ◽  
Carina Y. Heitmann ◽  
...  

Author(s):  
Brendan M. O’Flaherty ◽  
Chia-Chun Hsu ◽  
M. Anzar Abbas ◽  
Donald G. Rainnie

Fear is a critical emotional response that allows an organism to safely navigate through dangerous environments. The neural systems underlying the fear response have been well characterized, and include the amygdala, hippocampus, prefrontal cortex, bed nucleus of stria terminalis, nucleus accumbens, and others. While normally these brain regions coordinate to produce an appropriate fear response, the fear network in humans can become dysregulated after a traumatic event. The resulting phenotype of hyperarousal, avoidance, and re-experiencing of fear known as post-traumatic stress disorder (PTSD) is a growing problem in the United States. This chapter focuses on the role of the basolateral complex (BLC) of the amygdala, which has been implicated in the neuropathology of PTSD, particularly the hyperarousal, fear generalization, and fear extinction deficits characteristic of the disorder, as well as aspects of the microcircuitry, network connectivity, and neuromodulation of the BLC that may be involved in the pathophysiology of PTSD.


2017 ◽  
Author(s):  
Rachael M. Tillman ◽  
Melissa D. Stockbridge ◽  
Brendon M. Nacewicz ◽  
Salvatore Torrisi ◽  
Andrew S. Fox ◽  
...  

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


NeuroImage ◽  
2018 ◽  
Vol 168 ◽  
pp. 392-402 ◽  
Author(s):  
Adam X. Gorka ◽  
Salvatore Torrisi ◽  
Alexander J. Shackman ◽  
Christian Grillon ◽  
Monique Ernst

2017 ◽  
Vol 47 (15) ◽  
pp. 2675-2688 ◽  
Author(s):  
L. Brinkmann ◽  
C. Buff ◽  
K. Feldker ◽  
S. V. Tupak ◽  
M. P. I. Becker ◽  
...  

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.


2017 ◽  
Vol 48 (6) ◽  
pp. 919-928 ◽  
Author(s):  
M. Cano ◽  
P. Alonso ◽  
I. Martínez-Zalacaín ◽  
M. Subirà ◽  
E. Real ◽  
...  

BackgroundThe assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive–compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity.MethodsEighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses.ResultsIn comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus.ConclusionsThis study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.


Sign in / Sign up

Export Citation Format

Share Document