Strong mnemonic prediction errors increase cognitive control, attention, and arousal.

Ongoing experience is continuously processed in the context of past events. Divergence between current experience and memory-based predictions (i.e., a mnemonic prediction error; MPE) is theorized to be a signal for the hippocampus that encoding, as opposed to retrieval, should be prioritized. We asked how MPEs place demands on cognitive and neural resources beyond the hippocampus, and whether these demands differ as a function of prediction strength. We investigated these questions across two experiments, wherein we recorded scalp electroencephalography and/or pupillometry as 101 young human adults performed an associative memory task. Strong MPEs, more so than weak MPEs, increased physiological indices of cognitive control (frontal theta), attention (posterior alpha and pupil size), and arousal (pupil size). Trial-level pupil-linked MPE responses scaled with the amount of attention (posterior alpha) allocated during prediction generation. Finally, greater cognitive control (frontal theta) during strong MPEs promoted better learning of prediction violating (i.e., unexpected) stimuli. Collectively, these findings reveal how the mind and brain respond adaptively to violations of strong mnemonic predictions.