Dread of uncertain pain: An event-related potential study.

Humans experience more stress about uncertain situations than certain situations. However, the neural mechanism underlying the uncertainty of a negative stimulus has not been determined. In the present study, event-related potential was recorded to examine neural responses during the dread of unpredictable pain. We used a cueing paradigm in which predictable cues were always followed by electric shocks, unpredictable cues by electric shocks at a 50/50 ratio and safe cues by no electric shock. Visual analogue scales following electric shocks were presented to quantify subjective anxiety levels. The behavioral results showed that unpredictable cues evoked high-level anxiety compared with predictable cues in both painful and unpainful stimulation conditions. More importantly, the ERPs results revealed that unpredictable cues elicited a larger P200 at parietal sites than predictable cues. In addition, unpredictable cues evoked larger P200 compared with safe cues at frontal electrodes and compared with predictable cues at parietal electrodes. In addition, larger P3b and LPP were observed during perception of safe cues compared with predictable cues at frontal and central electrodes. The similar P3b effect was also revealed in the left sites. The present study underlined that the uncertain dread of pain was associated with threat appraisal process in pain system. These findings on early event-related potentials were significant for a neural marker and development of therapeutic interventions.