Prefrontal transthalamic uncertainty processing drives flexible switching.

Lam, Norman H; Mukherjee, Arghya; Wimmer, Ralf D; Nassar, Matthew R; Chen, Zhe Sage; Halassa, Michael M · Nature · 2025

basic_science · Level V

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Abstract

Making adaptive decisions in complex environments requires appropriately identifying sources of error<sup>1,2</sup>. The frontal cortex is critical for adaptive decisions, but its neurons show mixed selectivity to task features<sup>3</sup> and their uncertainty estimates<sup>4</sup>, 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<sup>5,6</sup> to reconfigure prefrontal executive control<sup>7</sup>. Overall, our work highlights a potential role for the thalamus in demixing cortical signals while providing a low-dimensional pathway for cortico-cortical communication.

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