The study investigates the neural mechanisms underlying placebo analgesia through functional magnetic resonance imaging (fMRI) experiments. Placebo treatments, which have no intrinsic pharmacological effects, can reduce pain perception by altering expectations. The researchers hypothesized that placebo analgesia would be associated with decreased brain activity in pain-sensitive regions such as the thalamus, insula, and anterior cingulate cortex (ACC), and increased activity in the prefrontal cortex (PFC) during pain anticipation. Two fMRI studies were conducted, each involving 24 participants, to test these hypotheses. In Study 1, participants received electric shocks and were informed about a placebo cream that was either effective or ineffective. Placebo-induced reductions in reported pain were correlated with decreased neural activity in pain-sensitive regions. In Study 2, a stronger placebo induction and a different pain modality were used, allowing for the analysis of the time course of placebo effects. Placebo-induced reductions in reported pain were found in the late phase of pain, suggesting that placebo effects may require a period of pain to develop. The study also found that the PFC, particularly the dorsolateral prefrontal cortex (DLPFC), showed increased activity during pain anticipation, which correlated with placebo-induced reductions in pain activity in pain-sensitive regions. These findings provide evidence that placebo analgesia involves both sensory and cognitive processes, with the PFC playing a crucial role in modulating pain experience through expectation and cognitive control.The study investigates the neural mechanisms underlying placebo analgesia through functional magnetic resonance imaging (fMRI) experiments. Placebo treatments, which have no intrinsic pharmacological effects, can reduce pain perception by altering expectations. The researchers hypothesized that placebo analgesia would be associated with decreased brain activity in pain-sensitive regions such as the thalamus, insula, and anterior cingulate cortex (ACC), and increased activity in the prefrontal cortex (PFC) during pain anticipation. Two fMRI studies were conducted, each involving 24 participants, to test these hypotheses. In Study 1, participants received electric shocks and were informed about a placebo cream that was either effective or ineffective. Placebo-induced reductions in reported pain were correlated with decreased neural activity in pain-sensitive regions. In Study 2, a stronger placebo induction and a different pain modality were used, allowing for the analysis of the time course of placebo effects. Placebo-induced reductions in reported pain were found in the late phase of pain, suggesting that placebo effects may require a period of pain to develop. The study also found that the PFC, particularly the dorsolateral prefrontal cortex (DLPFC), showed increased activity during pain anticipation, which correlated with placebo-induced reductions in pain activity in pain-sensitive regions. These findings provide evidence that placebo analgesia involves both sensory and cognitive processes, with the PFC playing a crucial role in modulating pain experience through expectation and cognitive control.