Resting-State Prefrontal Connectivity Varies With Placebo-Induced Hunger Expectations in Healthy Women

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). However, how these expectations influence intrinsic resting-state brain connectivity remains unclear. Here, we conducted seed-based resting-state functional connectivity analyses in 60 healthy, fasting female participants undergoing a placebo intervention that induced hunger expectations. In line with previously published results, the intervention induced hunger expectations and biased hunger sensations. We found that decreased hunger expectations attenuated mPFC-angular gyrus connectivity within the default mode network, while increased hunger expectations reduced vmPFC-dlPFC connectivity and enhanced dlPFC-thalamus coupling within frontoparietal and interoceptive networks. These results suggest that placebo-induced hunger expectations modulate prefrontal cortex connections with regions involved in valuation, cognitive control, and interoception. This modulation may reflect neural mechanisms by which beliefs shape bodily sensations under placebo conditions, advancing understanding of the neural substrates of expectation-driven sensory experiences.