Inter-individual differences in trait anxiety shape the functional connectivity between the bed nucleus of the stria terminalis and the amygdala during brief threat processing

Brinkmann, Leonie; Buff, Christine; Feldker, Katharina; Neumeister, Paula; Heitmann, Carina Yvonne; Hofmann, David; Bruchmann, Maximilian; Herrmann, Martin J.; Straube, Thomas

doi:10.1016/j.neuroimage.2017.10.054

Cited by 48 publications

(36 citation statements)

References 55 publications

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“…Further evidence for segregated information processing of the BNST as compared to the amygdala comes from several other studies that investigated the BOLD activity during induced states of phasic and sustained fear in humans. Those studies found the BNST to be activated during sustained fear states caused by unpredictable threat conditions (Alvarez, Chen, Bodurka, Kaplan, & Grillon, ), in anticipation of threatening events (e.g., Klumpers, Kroes, Baas, & Fernández, ; Somerville, Whalen, & Kelley, ) or aversive stimuli (e.g., Brinkmann, Buff, Feldker, et al, ; Brinkmann, Buff, Neumeister, et al, ; Brinkmann et al, ; Grupe, Oathes, & Nitschke, ; Herrmann et al, ; Somerville et al, ; Straube, Mentzel, & Miltner, ). Thus, the initiation of a general, longer lasting state of apprehension before and after a challenge to homeostasis has occurred, rather than immediate reactions to specific threats, seems to be a key difference between the amygdala and the BNST (Davis et al, ).…”

Section: Discussionmentioning

confidence: 99%

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

Hofmann

Straube

2019

Human Brain Mapping

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hofmann

Straube

2019

Human Brain Mapping

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“…In 343 particular, uncertainty about the timing of the onset of aversive events has been linked to measures 344 of anxiety in humans and other animals (Amadi et al, 2017;Bennett et al, 2018;Shankman et al, 345 2011). Interestingly, ambiguous threats (of varying types and degrees) are associated with 346 increases or changes in regional cerebral blood flow and functional connectivity in the primate 347 BNST (Alvarez et al, 2015(Alvarez et al, , 2011Brinkmann et al, 2018;Leonie 348 Brinkmann et al, 2017;Buff et al, 2017;Choi et al, 2014Choi et al, , 2012Coaster et al, 2011;Fox et al, 349 2018;Grupe et al, 2013;Herrmann et al, 2016;Kalin et al, 2008, Klumpers et al, 2017, 350 2015McMenamin et al, 2014;Meyer et al, 2018;Mobbs et al, 2010;Münsterkötter et al, 2015;351 Naaz et al, 2019;Pedersen et al, 2018Pedersen et al, , 2017Schlund et al, 2013;Sladky et al, 2018;Somerville 352 et al, 2010;Torrisi et al, 2018). In turn, BNST lesions or circuit inactivations reduce defensive 353 responding to contextual cues that poorly signal the imminence of the aversive US [ (Asok et al, 354 2018;Davis and Walker, 2014;Goode et al, 2015;Hammack et al, 2015;Luyten et al, 2011;355 Poulos et al, 2010;…”

Section: Backward Css Selectively Increase Fos Expression In Mpfc Affmentioning

confidence: 99%

“…Understanding the neural circuits underlying anxiety is important for 8 refining behavioral and pharmacotherapeutic treatments (Berridge, 2018;Deslauriers et al, 2017;9 Fanselow andPennington, 2018, 2017;Graham et al, 2014;LeDoux and Daw, 2018;Nees et al, 10 2015;Pine and LeDoux, 2017;Tye, 2018). Several recent studies have demonstrated changes in 11 the function of the bed nucleus of the stria terminalis (BNST) in individuals with post-traumatic 12 stress disorder (PTSD) and anxiety disorders (Andreescu et al, 2015;Brinkmann et al, 2018;L 13 Brinkmann et al, 2017;Leonie Brinkmann et al, 2017;Buff et al, 2017;Münsterkötter et al, 14 2015;Rabellino et al, 2018;Straube et al, 2007;Yassa et al, 2012). However, the conditions that 15 recruit the BNST to aversive learning and memory processes believed to underlie anxiety disorders 16 are still not understood (Avery et al, 2016(Avery et al, , 2014Ch'ng et al, 2018;Daniel and Rainnie, 2016;17 Davis et al, 2010;Fox and Shackman, 2017;Goode and Maren, 2017;Gungor and Paré, 2016;18 Lebow and Chen, 2016;Perusini and Fanselow, 2015;Shackman and Fox, 2016;Walker et al, 19 2009;Walker and Davis, 2008).…”

Section: Introductionmentioning

confidence: 99%

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

Goode

Ressler

Acca

et al. 2018

Preprint

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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.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.

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“…Although less intensively studied than the Ce, the BST is sensitive to emotional faces (Sladky et al, ), aversive images (Brinkmann et al, ), and a variety of threat‐related cues (Alvarez, Chen, Bodurka, Kaplan, & Grillon, ; Brinkmann et al, ; Choi, Padmala, & Pessoa, ; Grupe, Oathes, & Nitschke, ; Herrmann et al, ; Klumpers et al, ; McMenamin, Langeslag, Sirbu, Padmala, & Pessoa, ; Mobbs et al, ; Pedersen et al, ; Somerville, Whalen, & Kelley, ; Somerville et al, ). While imaging research hints at potential functional differences between the two regions (Alvarez et al, ; Fox et al, b; Meyer, Padmala, & Pessoa, ; Shackman et al, ; Somerville et al, ), methodological limitations preclude decisive inferences (Fox & Shackman, in press; Shackman & Fox, ).…”

Section: Introductionmentioning

confidence: 99%

“…While imaging research hints at potential functional differences between the two regions (Alvarez et al, ; Fox et al, b; Meyer, Padmala, & Pessoa, ; Shackman et al, ; Somerville et al, ), methodological limitations preclude decisive inferences (Fox & Shackman, in press; Shackman & Fox, ). Importantly, other work suggests that alterations in EAc function likely plays a key role in the development, maintenance, and recurrence of anxiety disorders, depression, and substance abuse (Avery et al, ; Brinkmann et al, , , ; Buff et al, ; Fox & Kalin, ; Kaczkurkin et al, ; Münsterkötter et al, ; Shackman et al, a, b; Stevens et al, ; Williams et al, ; Wise & Koob, ).…”

Section: Introductionmentioning

confidence: 99%

Intrinsic functional connectivity of the central extended amygdala

Tillman

Stockbridge

Nacewicz

et al. 2017

Human Brain Mapping

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The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a critical role in triggering fear and anxiety and is implicated in the development of a range of debilitating neuropsychiatric disorders. While it is widely believed that these disorders reflect the coordinated activity of widely distributed neural circuits, the functional architecture of the EAc network, and the degree to which the BST and the Ce show distinct patterns of functional connectivity, is unclear. Here, we used a novel combination of approaches to trace the connectivity of the BST and the Ce in 130 healthy, racially diverse, community-dwelling adults. Multiband imaging, high-precision registration techniques, and spatially unsmoothed data maximized 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, the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed stronger connectivity with the thalamus, striatum, periaqueductal gray, and several prefrontal territories. The only regions showing stronger functional connectivity with the Ce were neighboring regions of the dorsal amygdala, amygdalohippocampal area, and anterior hippocampus. 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 showcase image registration techniques which may be useful for researchers working with ‘de-identified’ neuroimaging data.

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Inter-individual differences in trait anxiety shape the functional connectivity between the bed nucleus of the stria terminalis and the amygdala during brief threat processing

Cited by 48 publications

References 55 publications

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

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

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

Intrinsic functional connectivity of the central extended amygdala

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