Temporal structure of brain oscillations predicts learned nocebo responses to pain

This study aimed to identify electrophysiological correlates of nocebo-augmented pain. Nocebo hyperalgesia (i.e., increases in perceived pain resulting from negative expectations) has been found to impact how healthy and patient populations experience pain and is a phenomenon that could be better understood in terms of its neurophysiological underpinnings. In this study, nocebo hyperalgesia was induced in 36 healthy participants through classical conditioning and negative suggestions. Electroencephalography was recorded during rest (pre- and post-acquisition) and during pain stimulation (baseline, acquisition, evocation) First, participants received baseline high thermal pain stimulations. During nocebo acquisition, participants learned to associate an inert gel applied to their forearm with administered high pain stimuli, relative to moderate intensity control stimuli administered without gel. During evocation, all stimuli were accompanied by moderate pain, to measure nocebo responses to the inert gel. Pre- to post-acquisition beta-band alterations in long-range temporal correlations (LRTC) were negatively associated with nocebo magnitudes. Individuals with strong resting LRTC showed larger nocebo responses than those with weaker LRTC. Nocebo acquisition trials showed reduced alpha power. Alpha power was higher while LRTC were lower during nocebo-augmented pain, compared to baseline. These findings support nocebo learning theories and highlight a role of nocebo-induced cognitive processing.