Computational signatures of uncertainty are reflected in motor cortex excitatory neurochemistry

N Nazia Jassim P Peter Thestrup Waade O Owen Parsons F Frederike H. Petzschner C Catarina Rua C Christopher T. Rodgers S Simon Baron-Cohen J John Suckling C Christoph Mathys R Rebecca P. Lawson

Abstract

Abstract 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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published November 04, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (10)

N

Nazia Jassim

P

Peter Thestrup Waade

O

Owen Parsons

F

Frederike H. Petzschner

C

Catarina Rua

C

Christopher T. Rodgers

S

Simon Baron-Cohen

J

John Suckling

C

Christoph Mathys

R

Rebecca P. Lawson