The role of the ventromedial prefrontal cortex (vmPFC) in human pavlovian threat conditioning has been relegated largely to the extinction or reversal of previously acquired stimulus–outcome associations. However, recent neuroimaging evidence questions this view by also showing activity in the vmPFC during threat acquisition. Here we investigate the casual role of vmPFC in the acquisition of pavlovian threat conditioning by assessing skin conductance response (SCR) and declarative memory of stimulus–outcome contingencies during a differential pavlovian threat-conditioning paradigm in eight patients with a bilateral vmPFC lesion, 10 with a lesion outside PFC and 10 healthy participants (each group included both females and males). Results showed that patients with vmPFC lesion failed to produce a conditioned SCR during threat acquisition, despite no evidence of compromised SCR to unconditioned stimulus or compromised declarative memory for stimulus–outcome contingencies. These results suggest that the vmPFC plays a causal role in the acquisition of new learning and not just in the extinction or reversal of previously acquired learning, as previously thought. Given the role of the vmPFC in schema-related processing and latent structure learning, the vmPFC may be required to construct a detailed representation of the task, which is needed to produce a sustained conditioned physiological response in anticipation of the unconditioned stimulus during threat acquisition.

SIGNIFICANCE STATEMENT Pavlovian threat conditioning is an adaptive mechanism through which organisms learn to avoid potential threats, thus increasing their chances of survival. Understanding what brain regions contribute to such a process is crucial to understand the mechanisms underlying adaptive as well as maladaptive learning, and has the potential to inform the treatment of anxiety disorders. Importantly, the role of the ventromedial prefrontal cortex (vmPFC) in the acquisition of pavlovian threat conditioning has been relegated largely to the inhibition of previously acquired learning. Here, we show that the vmPFC actually plays a causal role in the acquisition of pavlovian threat conditioning.

腹侧前额叶皮层（vmPFC）在人类帕夫洛夫病威胁调节中的作用主要归因于先前获得的刺激-结果关联的消灭或逆转。但是，最近的神经影像证据还通过显示威胁获取期间vmPFC中的活动来质疑这种观点。在这里，我们通过评估八名双侧vmPFC病变患者中的皮肤电导反应（SCR）和在不同的帕夫洛夫病威胁条件范式中的刺激性结果预见性记忆来评估vmPFC在获得帕夫洛夫病威胁条件中的偶然作用，其中10例患者患有双侧vmPFC病变PFC以外的病变和10名健康参与者（每组包括女性和男性）。结果显示，vmPFC病变患者在威胁获取期间未能产生条件性SCR，尽管没有证据表明SCR受到无条件刺激的折衷或刺激-结果意外事件的声明式记忆的折衷。这些结果表明，vmPFC在获取新学习成果方面起着因果作用，而不仅仅是先前认为的消亡或逆转先前获得的学习成果。考虑到vmPFC在与模式相关的处理和潜在结构学习中的作用，可能需要vmPFC来构造任务的详细表示，这对于在威胁获取期间预期到无条件刺激时产生持续的有条件生理响应是必需的。这些结果表明，vmPFC在获取新学习成果方面起着因果作用，而不仅仅是先前认为的消亡或逆转先前获得的学习成果。考虑到vmPFC在与模式相关的处理和潜在结构学习中的作用，可能需要vmPFC来构造任务的详细表示，这对于在威胁获取期间预期到无条件刺激时产生持续的有条件生理响应是必需的。这些结果表明，vmPFC在获取新学习成果方面起着因果作用，而不仅仅是先前认为的消亡或逆转先前获得的学习成果。考虑到vmPFC在与模式相关的处理和潜在结构学习中的作用，可能需要vmPFC来构造任务的详细表示，这对于在威胁获取期间预期到无条件刺激时产生持续的有条件生理响应是必需的。

意义声明巴甫洛夫威胁调节是一种适应性机制，通过该机制，生物可以学会避免潜在威胁，从而增加其生存机会。了解哪些大脑区域对这种过程有贡献，对于理解适应性和不良适应性学习的机制至关重要，并且有可能为焦虑症的治疗提供信息。重要的是，腹侧前额叶皮层（vmPFC）在获得帕夫洛夫病威胁调节中的作用已被主要归因于抑制先前获得的学习。在这里，我们表明vmPFC实际上在获取巴甫洛夫威胁条件中起着因果作用。