Chapter 8 – General discussion 263 Identifying cognitive mechanisms under the umbrella of associative learning Learning as a non-unitary phenomenon While it is apparent that nocebo effects involve a vast array of brain structures and processes 13,14, upon a systematic and detailed inspection of research to date, in chapter 3, we were able to synthesize a complete summary of those reproducible findings that paint a more concise and accurate picture of nocebo neurobiology. Our comprehensive review of the neuroscientific nocebo literature highlights a small number of consistent neuroimaging findings that tend to implicate specific cognitive correlates in the processing of nocebo pain. When discounting for known pain processing and sensory discrimination areas such as the somatosensory cortices and thalamus, the brain structures consistently implicated in nocebo hyperalgesia indicate a central role of learning by experience and cognitive pain modulation. When different types of learning and pain integration become involved in this process, evident by imaging findings –including our own– nocebo hyperalgesia can broadly be seen as a complex cognitive-sensory mechanism that arises through the integration of negative association learning and nociception. While learning was shown to broadly underlie nocebo responses on pain in chapter 3, learning is not a unitary phenomenon, but rather it is shown to rely on distinct and often competing mechanisms 8,15,16. For instance, even in basic non-conscious systems such as polymer networks and magnetic spins in solids, learning networks have been shown to memorize associative patterns from their environment based on specific learning modes that depend on particular contextual and stimulusspecific factors 17. Higher order systems such as the human brain have been shown to learn and retrieve information based on distinct and often cooperating neural systems 18,19. In our experimental studies we set out to examine specific learning mechanisms and their unique
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