Journal
CEREBRAL CORTEX
Volume 25, Issue 10, Pages 3903-3910Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhu275
Keywords
amygdala; conditioning; nocebo effect; placebo effect; subliminal perception
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Funding
- COFAS Marie Curie Postdoc Program and Osher Center for Integrative Medicine at Karolinska Institutet [R01AT006364, R21AT004497, R03AT218317, K24 AT004095, R01AT005280, UL1 RR025758-01, P41RR14075]
- Karolinska Institute
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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.
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