Jensen Karin B, Kaptchuk Ted J, Chen Xiaoyan, Kirsch Irving, Ingvar Martin, Gollub Randy L, Kong Jian
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA Program in Placebo Studies, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA.
Program in Placebo Studies, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA.
Cereb Cortex. 2015 Oct;25(10):3903-10. doi: 10.1093/cercor/bhu275. Epub 2014 Dec 1.
Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science.
人类行为的基本方面在意识觉知之外发挥作用。然而，人类的条件反应理论，如安慰剂和反安慰剂对疼痛的影响，非常强调对触发反应的情境线索的意识识别。在此，我们利用功能磁共振成像对健康参与者进行研究，以探究参与条件性疼痛反应非意识激活的神经通路。与条件性安慰剂镇痛的意识激活相比，非意识激活与眶额皮质的激活增加有关，眶额皮质是一个与情感脑区和基本奖赏处理有直接联系的结构。在非意识反安慰剂效应期间，丘脑、杏仁核和海马体的激活增加。与之前关于人类条件作用的假设相反，我们的结果表明，条件性疼痛反应可以在独立于意识觉知的情况下被诱发，并且我们的结果表明非意识和意识条件反应的神经通路存在分层激活。证明人类大脑具有对条件线索做出反应的非意识机制，对联想学习在行为医学和精神病学中的作用具有重要意义。我们的结果也可能为从动物到人类的转化研究开辟新的途径，因为人类意识和动物认知是所有行为科学中固有的悖论。
