Neural coding of choice and outcome are modulated by uncertainty in orbitofrontal but not secondary motor cortex

Juan Luis Romero-Sosa (), Alex Yeghikian, Andrew M. Wikenheiser, Hugh T. Blair and Alicia Izquierdo ()
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Juan Luis Romero-Sosa: Los Angeles
Alex Yeghikian: Los Angeles
Andrew M. Wikenheiser: Los Angeles
Hugh T. Blair: Los Angeles
Alicia Izquierdo: Los Angeles

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Orbitofrontal cortex (OFC) and secondary motor cortex (M2) are both implicated in flexible reward learning but the conditions that differentially recruit these regions are not fully understood. We imaged calcium activity from single neurons in rat OFC or M2 during de novo learning of increasingly uncertain reward probability schedules. Predictions of choice were decoded from M2 neurons with high accuracy under all certainty conditions, but were more accurately decoded from OFC neurons under greater uncertainty. Decoding accuracy of choice and outcome was predicted by behavioral strategies Win-Stay and Lose-Shift in OFC, but not M2. Whereas chemogenetic inhibition of OFC neurons attenuated learning across all schedules, M2 neurons were found to support learning in only the most certain reward schedule. Thus, OFC neurons preferentially encode choices and outcomes that foster a greater reliance on adaptive strategies under uncertainty. This reveals a functional heterogeneity within frontal cortex in support of flexible learning.

Date: 2025
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DOI: 10.1038/s41467-025-63866-5

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