Task-switching is a fundamental cognitive ability which requires animals to update their knowledge of current rules, allowing flexible behaviour in a changing environment1. This is often achieved through evaluating discrepancies between observed and expected events. The anterior cingulate cortex (ACC) has a key role in processing such discrepancies, or prediction errors2–12. However, the neural circuit mechanisms underlying task-switching are largely unknown. Here we show that activity in the ACC induced by the absence of expected stimuli is necessary for rapid task-switching. Mice trained to perform a block-wise set-shifting task typically required a single experience of an expectation violation, or prediction error to accurately switch between responding to the same stimuli using distinct rules. Neurons in the ACC explicitly represented these prediction errors, and their activity was predictive of successful one-shot behavioural transitions. Prediction error signals were projection targetspecific, constrained in their spatio-temporal spread across cortex, and heavily disrupted by VIP interneuron perturbation. Optogenetic silencing and single-trial un-silencing revealed that the requirement of the ACC in task-switching was restricted to the epochs when neural prediction error signals were observed. These results reveal a dedicated circuitry promoting the transition between distinct cognitive states.

Attentional modulation of sensory processing is a key feature of cognition, yet its neural circuit basis is poorly understood. A candidate mechanism is the disinhibition of pyramidal cells through vasoactive intestinal peptide (VIP) and somatostatin (SOM) positive interneurons. However, the interaction of attentional modulation and VIP-SOM disinhibition has never been directly tested. We used all-optical methods to bi-directionally manipulate VIP interneuron activity as mice performed an attention switching task. We measured the activity of VIP, SOM and parvalbumin (PV) positive interneurons and pyramidal neurons identified in the same tissue and found that although activity in all cell classes was modulated by both attention and VIP manipulation, their effects were orthogonal. Attention and VIP-SOM disinhibition relied on distinct patterns of changes in activity and reorganisation of interactions between inhibitory and excitatory cells. These results reveal the remarkable ability of cortical circuits to multiplex strong yet non-interacting modulations in the same neural population.