Phasic norepinephrine is a neural interrupt signal for unexpected events in rapidly unfolding sensory sequences - evidence from pupillometry

The ability to track the statistics of our surroundings is a key computational challenge. A prominent theory (Dayan & Yu, 2006) proposes that the brain monitors for 'unexpected uncertainty' - events which deviate substantially from model predictions, indicating model failure. Norepinephrine (NE) is thought to play a key role in this process by serving as an interrupt signal, initiating model-resetting. However, evidence is from paradigms where participants actively monitored stimulus statistics. To determine whether NE routinely reports the statistical structure of our surroundings, even when not behaviourally relevant, we used rapid tone-pip sequences that contained perceptually salient pattern-changes associated with abrupt structural violations vs. emergence of regular structure. Phasic pupil dilations (PDR) were monitored to assess NE. We reveal a remarkable specificity: When not behaviourally relevant, only abrupt structural violations evoked a PDR. The results demonstrate that NE tracks 'unexpected uncertainty' on rapid time scales relevant to sensory signals.