From Fear to Safety and Back: Reversal of Fear in the Human Brain
From Fear to Safety and Back: Reversal of Fear in the Human Brain
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DOI：
10.1523/jneurosci.2265-08.2008
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发表时间：
2008-11-05
影响因子：
5.3
通讯作者：
Phelps, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Schiller, Daniela;Levy, Ifat;Phelps, Elizabeth A.
恐惧学习是一个快速而持久的过程，可以促进对威胁的防御，减少重新学习危险的需要。然而，当环境发生变化时，灵活地调整恐惧行为也很重要。事实上，不能适应不断变化的环境可能会导致焦虑症。恐惧调节的一个核心但被忽视的方面是，当曾经具有威胁性的刺激变得安全，或者曾经安全的刺激变得具有威胁性时，人们能够灵活地将恐惧反应从一种刺激转移到另一种刺激。在这些情况下，恐惧的抑制和恐惧反应的发展同时发生，但针对不同的目标，需要在持续的压力下做出准确的反应。迄今为止，对恐惧调节的研究主要集中在通过使用灭绝等范式从恐惧转向安全，从而减少恐惧。本研究的目的是追踪当这些转变同时发生时，从恐惧到安全以及从安全到恐惧的动态转变。我们将功能性神经成像与恐惧调节逆转范式结合使用。我们的研究结果揭示了腹内侧前额叶皮层在先前预测危险的安全刺激和“幼稚”安全刺激之间的独特分离。我们发现杏仁核和纹状体的反应跟踪恐惧预测刺激，灵活地从一个预测刺激切换到另一个预测刺激。此外，与反转学习相关的预测误差与纹状体激活相关。这些结果阐明了恐惧是如何重新调整以适当地跟踪环境变化的，以及灵活控制恐惧的大脑机制。
Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a "naive" safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear.