How human amygdala and bed nucleus of the stria terminalis may drive distinct defensive responses
Number of pages
SourceThe Journal of Neuroscience, 37, 40, (2017), pp. 9645-9656
Article / Letter to editor
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SW OZ BSI KLP
Donders Centre for Cognitive Neuroimaging
PI Group Memory and Emotion
The Journal of Neuroscience
Subject130 000 Cognitive Neurology & Memory; Experimental Psychopathology and Treatment; Radboudumc 13: Stress-related disorders DCMN: Donders Center for Medical Neuroscience
The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we utilized data from two independent functional magnetic resonance imaging studies (N=108 males & N=70 (45 females)) to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from sample 2 (N=48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST towards the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance towards acute threat responding and via that route predispose for affective disorder.
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