Prefrontal transthalamic uncertainty processing drives flexible switching

Norman H. Lam, Arghya Mukherjee, Ralf D. Wimmer, Matthew R. Nassar, Zhe Sage Chen and Michael M. Halassa ()
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Norman H. Lam: Tufts University
Arghya Mukherjee: Tufts University
Ralf D. Wimmer: Tufts University
Matthew R. Nassar: Brown University
Zhe Sage Chen: New York University
Michael M. Halassa: Tufts University

Nature, 2025, vol. 637, issue 8044, 127-136

Abstract: Abstract Making adaptive decisions in complex environments requires appropriately identifying sources of error1,2. The frontal cortex is critical for adaptive decisions, but its neurons show mixed selectivity to task features3 and their uncertainty estimates4, 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 monitoring5,6 to reconfigure prefrontal executive control7. Overall, our work highlights a potential role for the thalamus in demixing cortical signals while providing a low-dimensional pathway for cortico-cortical communication.

Date: 2025
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DOI: 10.1038/s41586-024-08180-8

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