82 Functional imaging Functional Magnetic Resonance Imaging (fMRI) is a technique that can map brain function by detecting blood-oxygen-level dependent (BOLD) changes and thereby indirectly measuring brain activity 52,53. The measurement of BOLD activity in the brain has helped researchers explore functional brain correlates, from sensory perception to higher cognitive functions such as the formation of expectations 1,54–56. When comparing the frequently used brain imaging techniques EEG and fMRI, fMRI provides higher spatial resolution whereas EEG provides greater temporal resolution. MRI also enables high resolution structural brain imaging. In the 12 studies reviewed below, fMRI has shed light onto some of the functional and anatomical similarities and differences between nocebo hyperalgesia and related effects such as placebo analgesia. These studies used various nocebo induction methods: 3 used conditioning 57–59, 4 used negative suggestions 8,20,60,61, and 5 used a combination of conditioning and negative suggestions 9,19,62–64. Studies that described nocebo effects in somatic pain, visceral pain, or spinal pain are summarized separately because of the methodological differences in the study designs and their proposed underlying mechanisms. Eight studies examined brain activation in response to nocebo hyperalgesia for somatic pain using fMRI. In a study by Keltner and colleagues (2006), participants were conditioned to associate two distinct visual cues (red or blue) with thermal pain stimuli of high and low intensity, respectively. The imaging data of the nocebo evocation phase revealed that during high intensity pain stimulation, high and low pain expectations produced differential brain activations. The caudal ACC, the cerebellum, and the dorsolateral pontomesencephalic region had increased BOLD activation when expectations were for higher pain intensity. During low intensity pain stimulation, the two expectation levels did however not yield significant differences in BOLD activations.
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