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ORIGINAL RESEARCH article

Front. Neurosci.

Sec. Decision Neuroscience

Volume 19 - 2025 | doi: 10.3389/fnins.2025.1592015

This article is part of the Research TopicDecision making and its pathologies: a translational animal-to-human overviewView all articles

Anterior insula glutamate complex is associated with psychopathology scores through overestimating errors

Provisionally accepted
  • 1Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
  • 2Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
  • 3California Institute of Technology, Pasadena, California, United States

The final, formatted version of the article will be published soon.

Despite the insights provided by functional magnetic resonance spectroscopy (fMRS), the influence of neurochemical mechanisms on mental health and decision-making remains underexplored. This study examined whether baseline glutamate/glutamine (Glx) concentrations are related to general anxiety and depression and how these concentration change during learning involving gains and losses. We found that Glx concentration in the anterior insular cortex (AIC), but not the medial prefrontal cortex (mPFC), is positively associated with the general psychopathological factor score (G-score) for anxiety and depression. Moreover, the relationship between AIC Glx and G-score is mediated by error sensitivity. Post-hoc analysis revealed that AIC Glx levels decreased during gain learning. These findings suggest that Glx-related error sensitivity in the AIC is linked to general psychopathology, highlighting the AIC as a potential target for glutamate-mediated therapies for anxiety and depression.

Keywords: Reward Learning, General psychopathology, Functional MRS, Glutamate, Error sensitivity

Received: 11 Mar 2025; Accepted: 04 Jun 2025.

Copyright: © 2025 Park, Kim, Kim, Kim and Jeong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Bumseok Jeong, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

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