Proximal threats promote enhanced acquisition and persistence of reactive fear-learning circuits
Proximal threats promote enhanced acquisition and persistence of reactive fear-learning circuits
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DOI：
10.1073/pnas.2004258117
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发表时间：
2020-07-14
影响因子：
11.1
通讯作者：
LaBar, Kevin S.
中科院分区：
文献类型：
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作者：
Faul, Leonard;Stjepanovic, Daniel;LaBar, Kevin S.
身体上接近创伤性事件会增加伴随的压力症状的严重程度，这种影响让人想起基于威胁免疫的进化配置的恐惧反应。尽管恐惧条件反射被广泛采用为压力和焦虑障碍的模型系统，但研究尚未描述威胁接近如何影响人类大脑中恐惧获得和消除的机制。在功能磁共振成像（fMRI）中，我们利用三维（3D）虚拟现实技术来操纵健康成人在虚拟世界中导航时对同种威胁的自我中心距离。与理论预测一致，近端威胁通过将大脑中的条件学习从认知回路转移到反应性恐惧回路，并在恐惧获得和消除过程中减少杏仁核-皮层连接，从而增强了恐惧获得。通过对习得阶段和消退阶段表征模式相似性的分析，我们进一步证明，近端威胁通过小脑中条件学习的持续多元表征损害了消退效果，这预示了对后来恐惧恢复的易感性。这些结果表明，在近距离接触时遇到的条件威胁对消退学习更有抵抗力，并表明典型的与恐惧学习相关的典型神经回路需要额外考虑更反应性的神经恐惧系统，以充分解释这种影响。
Physical proximity to a traumatic event increases the severity of accompanying stress symptoms, an effect that is reminiscent of evolutionarily configured fear responses based on threat immi-nence. Despite being widely adopted as a model system for stress and anxiety disorders, fear-conditioning research has not yet char-acterized how threat proximity impacts the mechanisms of fear acquisition and extinction in the human brain. We used three-dimensional (3D) virtual reality technology to manipulate the ego-centric distance of conspecific threats while healthy adult partici-pants navigated virtual worlds during functional magnetic resonance imaging (fMRI). Consistent with theoretical predictions, proximal threats enhanced fear acquisition by shifting conditioned learning from cognitive to reactive fear circuits in the brain and reducing amygdala-cortical connectivity during both fear acquisi-tion and extinction. With an analysis of representational pattern similarity between the acquisition and extinction phases, we fur-ther demonstrate that proximal threats impaired extinction effi-cacy via persistent multivariate representations of conditioned learning in the cerebellum, which predicted susceptibility to later fear reinstatement. These results show that conditioned threats encountered in close proximity are more resistant to extinction learning and suggest that the canonical neural circuitry typically associated with fear learning requires additional consideration of a more reactive neural fear system to fully account for this effect.