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

Abstract

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.

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

“…This suggests a unique role for BNST-projecting neurons of the IL [which 423 appear to be glutamatergic: (Crowley et al, 2016;Glangetas et al, 2017)] in processing excitatory 424 backwards CSs. There is growing evidence for a regulatory role for prefrontal connections to the 425 BNST in stress and anxiety-like behavior (Fox et al, 2010;Glangetas et al, 2017Glangetas et al, , 2013Johnson 426 et al, 2018;Kinnison et al, 2012;Motzkin et al, 2015;Naaz et al, 2019;Radley et al, 2009), the 427 present data adds to this work by suggesting that the IL may be involved in generating freezing 428 and/or stress responding to the backward CS. This would stand in contrast to considerable data 429 indicating that the IL is involved in the inhibition of freezing behavior after extinction, for example 430 (Milad and Quirk, 2002;Quirk and Mueller, 2008).…”

“…This contrasts with prior work suggesting that the BNST 367 only mediates freezing behavior to long-duration cues or contexts (Hammack et al, 2015;Waddell 368 et al, 2006). However, recent data in other paradigms suggest a role for the BNST in the processing 369 of responses to relatively brief threat stimuli (Brinkmann et al, 2018;Choi et al, 2014;Haufler et 370 al., 2013;Kinnison et al, 2012;Kiyokawa et al, 2015;Klumpers et al, 2017;Luyck et al, 2018bLuyck et al, , 371 2018aNaaz et al, 2019). Together, these data suggest that stimulus duration is not necessarily a 372 determinant of BNST involvement.…”

Stria terminalis, amygdala, and temporoparietal junction networks facilitate efficient emotion processing under expectations

“…Evidence suggests that these two regions have distinct roles in threat perception, specifically phasic versus sustained response(Alvarez, Chen, Bodurka, Kaplan, & Grillon, 2011;Herrmann et al, 2016;Naaz, Knight, & Depue, 2019). In sum, we provide evidence that the extended amygdala circuitry facilitates speed of response in threatening situations and, for the first time, highlight a key role for the stria terminalis in the efficient recognition of emotion under threat.…”

“…The extended amygdala network includes the amygdala and the BNST. Evidence suggests that these two regions have distinct roles in threat perception, specifically phasic versus sustained response (Alvarez, Chen, Bodurka, Kaplan, & Grillon, 2011;Herrmann et al, 2016;Naaz, Knight, & Depue, 2019). The most recent paper by Naaz et al (2019) found that the amygdala is involved in phasic responses to explicit (cued) threat and the BNST involved in sustained responses to ambiguous threat.…”

“…S5 [Color figure can be viewed at wileyonlinelibrary.com]response times for happy videos. The most recent paper byNaaz et al (2019) found that the amygdala is involved in phasic responses to explicit (cued) threat and the BNST involved in sustained responses to ambiguous threat. Furthermore, we advance on current knowledge by demonstrating differential influence of the rAMY-limbic and rTPJ-ventral attention network on fast processing of anger, depending on if anger is congruent or incongruent with prior expectations, respectively.We found that both functional and structural connectivity within the extended amygdala network facilitate speed of emotion processing in threatening conditions.…”