Scott et al. (2007) examined the role of the nucleus accumbens (NAC), a region of the brain involved with reward expectation, in the formation of expectancy effects (placebo effects). Using functional molecular imaging, activation of NAC dopamine (DA) release was observed during placebo administration and related to its anticipated effects and placebo effect development. In additional functional MRI studies, the expectation of monetary gain increased NAC synaptic activity proportional to placebo- induced DA release. This research demonstrates strong support for the magnitude of expectation in relation to brain reward mechanisms.
Volkow et al. (2003) investigated how expectation affects the response to the stimulant drug methylphenidate in 25 cocaine abusers. The effects of the drug on brain glucose metabolism and on its reinforcing effects (self-reports of drug effects) were evaluated in four conditions: (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving the drug; (3) expecting the drug and receiving the drug methylphenidate; (4) expecting the drug and receiving placebo. The results indicated increases in metabolism were 50% larger when methylphenidate was expected than when it was not. These differences were significant in cerebellum (vermis) and thalamus. In contrast, unexpected methylphenidate showed larger increases in left lateral orbitofrontal cortex than when it was expected. Drug-induced increases in self-reports of being high were also 50% greater when subjects expected to receive it than when they did not. Self-reports of being high were significantly correlated with the metabolic increases in thalamus but not in cerebellum. A key finding in this study is that expectation heightens the effects of methylphenidate in the brain and its reinforcing effects.
An event-related fMRI study was used to measure the effects of cognitive (semantic) priming on the neural responses to a delivery of odors (de Araujo, Rolls, Velazco, Margot, Cayeux, 2005). Odors were presented with descriptors on a screen. A test odor was labeled on different trials as “cheddar cheese” or “body odor.” The same labels were paired with delivery of clean air in different trials. Alpha-ionone (pleasant, labeled “flowers”) and Octanol (unpleasant, labeled “burned plastic”) were used as references for pleasant and unpleasant stimuli for the psychophysics and neuroimaging. The participants rated the test odor as significantly more unpleasant when labeled “body odor” than when labeled “cheddar cheese.” The fMRI showed that the rostral anterior cingulate cortex / medial orbitofrontal cortex was significantly more activated by the test stimulus and by clean air when labeled “cheddar cheese” than when labeled “body odor.” Recent neuroimaging studies have demonstrated that pleasant odors preferentially activate medial orbitofrontal regions, while unpleasant odors activate lateral regions. The findings of this study suggest expectation of odor may have an influence on flavor perception, as smell is a key component involved with flavor perception.
References available upon request