Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Biol Psychiatry. 2012 Aug 15;72(4):266-72. doi: 10.1016/j.biopsych.2012.03.007. Epub 2012 Apr 12.
Heightened fear and anxiety are core symptoms of a variety of neuropsychiatric disorders. They are associated with structural and activity changes throughout neural circuitry that includes the ventral and medial prefrontal cortices (PFC), the amygdala, and hippocampus. Although the contributions of the medial PFC, amygdala, and hippocampus to fear and anxiety have been studied extensively with animal models, the selective roles of the ventral PFC-including the ventrolateral prefrontal cortex (vlPFC) and orbitofrontal cortex-are poorly understood.
We investigated the effects of selective excitotoxic lesions of either the vlPFC or anterior orbitofrontal cortex (antOFC) on anxious behavior and Pavlovian conditioned autonomic and behavioral fear responses in the New World primate, the common marmoset.
Both vlPFC and antOFC lesions resulted in stronger, less adaptable conditioned fear responses. They also heightened the anxiety responses of a marmoset to a human intruder. In contrast, only a lesion of the vlPFC affected the coping style that a marmoset displayed in the presence of the human intruder, increasing the likelihood of proactive mobbing.
These results suggest that both the antOFC and vlPFC can downregulate fear and anxiety and, together, provide necessary but independent contributions to the top-down control of negative emotion.
高度的恐惧和焦虑是多种神经精神疾病的核心症状。它们与包括腹侧和内侧前额叶皮层（PFC）、杏仁核和海马体在内的整个神经回路的结构和活动变化有关。尽管动物模型已经广泛研究了内侧 PFC、杏仁核和海马体对恐惧和焦虑的贡献，但腹侧 PFC 的选择性作用——包括腹外侧前额叶皮层（vlPFC）和眶额皮层——知之甚少。
我们研究了选择性兴奋性毒性损伤 vlPFC 或前眶额皮层（antOFC）对新世界灵长类动物——普通狨猴的焦虑行为以及巴甫洛夫条件性自主和行为恐惧反应的影响。
vlPFC 和 antOFC 损伤均导致更强、适应性更差的条件性恐惧反应。它们还增加了狨猴对人类入侵者的焦虑反应。相比之下，只有 vlPFC 的损伤会影响狨猴在人类入侵者面前的应对方式，增加主动挑衅的可能性。
这些结果表明，antOFC 和 vlPFC 均可下调恐惧和焦虑，共同为负性情绪的自上而下控制提供必要但独立的贡献。
