Prefrontal transthalamic uncertainty processing drives flexible switching.

Making adaptive decisions in complex environments requires appropriately identifying sources of error. The frontal cortex is critical for adaptive decisions, but its neurons show mixed selectivity to task features and their uncertainty estimates, raising the question of how errors are attributed to their most likely causes. Here, by recording neural responses from tree shrews (Tupaia belangeri) performing a hierarchical decision task with rule reversals, we find that the mediodorsal thalamus independently represents cueing and rule uncertainty. This enables the relevant thalamic population to drive prefrontal reconfiguration following a reversal by appropriately attributing errors to an environmental change. Mechanistic dissection of behavioural switching revealed a transthalamic pathway for cingulate cortical error monitoring to reconfigure prefrontal executive control. Overall, our work highlights a potential role for the thalamus in demixing cortical signals while providing a low-dimensional pathway for cortico-cortical communication.