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A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.
Cereb Cortex. 2015 Oct; 25(10):3903-10.CC

Abstract

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.

Authors+Show Affiliations

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.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 School of Psychology, Plymouth University, Plymouth PL4 8AA, UK.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm 17176, Sweden.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25452576

Citation

Jensen, Karin B., et al. "A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses." Cerebral Cortex (New York, N.Y. : 1991), vol. 25, no. 10, 2015, pp. 3903-10.
Jensen KB, Kaptchuk TJ, Chen X, et al. A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses. Cereb Cortex. 2015;25(10):3903-10.
Jensen, K. B., Kaptchuk, T. J., Chen, X., Kirsch, I., Ingvar, M., Gollub, R. L., & Kong, J. (2015). A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses. Cerebral Cortex (New York, N.Y. : 1991), 25(10), 3903-10. https://doi.org/10.1093/cercor/bhu275
Jensen KB, et al. A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses. Cereb Cortex. 2015;25(10):3903-10. PubMed PMID: 25452576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses. AU - Jensen,Karin B, AU - Kaptchuk,Ted J, AU - Chen,Xiaoyan, AU - Kirsch,Irving, AU - Ingvar,Martin, AU - Gollub,Randy L, AU - Kong,Jian, Y1 - 2014/12/01/ PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2016/7/2/medline KW - amygdala KW - conditioning KW - nocebo effect KW - placebo effect KW - subliminal perception SP - 3903 EP - 10 JF - Cerebral cortex (New York, N.Y. : 1991) JO - Cereb. Cortex VL - 25 IS - 10 N2 - 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. SN - 1460-2199 UR - https://www.unboundmedicine.com/medline/citation/25452576/A_Neural_Mechanism_for_Nonconscious_Activation_of_Conditioned_Placebo_and_Nocebo_Responses_ L2 - https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bhu275 DB - PRIME DP - Unbound Medicine ER -