Nature Communications

Computational signatures of uncertainty are reflected in motor cortex excitatory neurochemistry

2025-11-04

How individuals process and respond to uncertainty has important implications for cognition and mental health. Here, we use computational phenotyping to examine inter-individual differences in uncertainty processing in relation to neurometabolites and trait anxiety in humans. We introduce a categorical state-transition extension of the Hierarchical Gaussian Filter to model individuals’ evolving beliefs about transition probabilities in a four-choice probabilistic sensorimotor learning task with a reversal. Using 7-Tesla Magnetic Resonance Spectroscopy, we measure neurotransmitter levels in the primary motor cortex. Model-based results reveal dynamic belief updating in response to environmental changes. We further find region-specific relationships between baseline primary motor cortex glutamate+ glutamine levels and prediction errors and volatility beliefs. High trait anxiety is associated with faster post-reversal responses. This study establishes a direct neurochemical correlate of hierarchical belief updating, identifying motor cortex glutamate + glutamine as an important neural marker of inter-individual differences in uncertainty processing.

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DOI https://doi.org/10.1038/s41467-025-64702-6