Chapter 8 – General discussion 257 bad outcome. These two groups, as expected, reported overall higher levels of fear of pain, and the higher-pain group also responded with significantly larger nocebo hyperalgesia. The results further indicated that more research is needed to unravel the intricacies of central pain integration with cognitive-emotional factors. The value of utilizing known imaging markers to measure fear of pain on a biobehavioral level, led to the novel approach of using electrophysiological biomarkers to further understand pain integration and processing under nocebo hyperalgesic conditions. In the next chapter, we thus applied imaging of the brain by use of EEG, in order to better understand how neurocognitive processing affects pain experiences under hyperalgesic conditions. Chapter 6 examines the electrophysiology of learned pain responses through the lens of the currently known markers of pain and of emotional processing. We utilized sophisticated EEG biomarkers to characterize complex electrophysiological patterns during baseline pain perception, learning, and then evocation of nocebo responses. We additionally measured and computed brain electrophysiology at rest, before and after the experimental paradigm, to explore baseline characteristics that may modulate the acquisition of hyperalgesic effects and to examine the changes from before to after nocebo acquisition. Indeed, we found that individuals who exhibit higher complexity of neuronal patterns of oscillations at baseline showed larger nocebo responses. At the same time, differences were also found in how the brain processes increased pain stimulation at baseline versus a noceboaugmented perceived pain increase. EEG provided several novel insights into the neurophysiological phenotype of nocebo hyperalgesia, enabling us to paint an initial broad picture of a complex neural signature of nocebo hyperalgesia. Questions were also raised by this study, as EEG methods encounter limitations in terms of localizing effects in the brain, as well as in measuring specific functional contributions of
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