Prefrontal cortex resting-state connectivity is moderated by hunger expectations induced by a placebo intervention in healthy female participants.
Placebo effects, in which a patient's symptoms and subjective well-being improve in response to an inactive treatment, medication, or intervention (a placebo), are well known in clinical research. Basic research in human cognition and neuroscience has shown that these effects are linked to prognostic expectations of effectiveness and to recruitment of prefrontal cortex regions, including the medial (mPFC), ventromedial (vmPFC), and dorsolateral prefrontal cortex (dlPFC). Here, we examined how the intrinsic functional connectivity of these three brain regions at rest, in the absence of any explicit task, was affected by internal beliefs such as placebo-induced hunger expectations. We conducted a seed-based resting-state functional connectivity analysis in 60 healthy female participants who underwent a placebo intervention targeting their hunger. In line with previously published results, the intervention induced hunger expectations and biased hunger sensations. Importantly, these effects were underpinned by attenuated functional connectivity between the mPFC and the angular gyrus within the default mode network the more participants expected the placebo to decrease their hunger. Hunger-increasing expectations attenuated connectivity between the vmPFC and the dm/dlPFC within the frontoparietal network and increased connectivity between the dlPFC and the thalamus. These results suggest that placebo-induced hunger expectations shift the way the prefrontal cortex connects to other brain regions associated with valuation, cognitive control, and interoception. This evidence sheds light on how the brain may translate incoming sensory information into biased sensations under placebo conditions and improves our understanding of the neural and psychological factors that influence a person's response to a placebo.