Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function

  1. Lilian Aline Weber  Is a corresponding author
  2. Sara Tomiello
  3. Dario Schöbi
  4. Katharina V. Wellstein
  5. Daniel Mueller
  6. Sandra Iglesias
  7. Klaas Enno Stephan
  1. University of Zurich, Switzerland
  2. University Hospital of Zurich, Switzerland

Abstract

The auditory mismatch negativity (MMN) has been proposed as a biomarker of NMDA receptor (NMDAR) dysfunction in schizophrenia. Such dysfunction may be caused by aberrant interactions of different neuromodulators with NMDARs, which could explain clinical heterogeneity among patients. In two studies (N=81 each), we used a double-blind placebo-controlled between-subject design to systematically test whether auditory mismatch responses under varying levels of environmental stability are sensitive to diminishing and enhancing cholinergic vs. dopaminergic function. We found a significant drug x mismatch interaction: while the muscarinic acetylcholine receptor antagonist biperiden delayed and topographically shifted mismatch responses, particularly during high stability, this effect could not be detected for amisulpride, a dopamine D2/D3 receptor antagonist. Neither galantamine nor levodopa, which elevate acetylcholine and dopamine levels, respectively, exerted significant effects on MMN. This differential MMN sensitivity to muscarinic versus dopaminergic receptor function may prove useful for developing tests that predict individual treatment responses in schizophrenia.

Data availability

All raw data (EEG data, behavior) used for this manuscript are available at https://research-collection.ethz.ch/handle/20.500.11850/477685, adhering to the FAIR (Findable, Accessible, Interoperable, and Re-usable) data principles. The analysis code that reproduces the results presented here is publicly available on the GIT repository of ETH Zurich at https://gitlab.ethz.ch/tnu/code/weber-muscarinic-mmn-erp-2021.

The following data sets were generated

Article and author information

Author details

  1. Lilian Aline Weber

    Translational Neuroimaging Unit (TNU), Institute for Biomedical EngineeringInstitute for Biomedical Engineering, University of Zurich, Zurich, Switzerland
    For correspondence
    weber@biomed.ee.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9727-9623
  2. Sara Tomiello

    Translational Neuroimaging Unit (TNU), Institute for Biomedical Engineering, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Dario Schöbi

    Translational Neuroimaging Unit (TNU), Institute for Biomedical Engineering, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Katharina V. Wellstein

    Translational Neuroimaging Unit (TNU), Institute for Biomedical Engineering, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel Mueller

    Institute for Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Sandra Iglesias

    Translational Neuroimaging Unit (TNU), Institute for Biomedical Engineering, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1778-7239
  7. Klaas Enno Stephan

    Translational Neuroimaging Unit (TNU), Institute for Biomedical Engineering, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8594-9092

Funding

University of Zurich (N/A)

  • Klaas Enno Stephan

René und Susanne Braginsky Stiftung (N/A)

  • Klaas Enno Stephan

Max Planck Institute for Metabolism Research (open access funding)

  • Klaas Enno Stephan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All participants gave written informed consent prior to data acquisition and were financially reimbursed for their participation. The study was approved by the cantonal Ethics Committee of Zurich (KEK-ZH-Nr. 2011-0101/3).

Reviewing Editor

  1. Jonas Obleser, University of Lübeck, Germany

Version history

  1. Preprint posted: March 20, 2021 (view preprint)
  2. Received: October 25, 2021
  3. Accepted: April 26, 2022
  4. Accepted Manuscript published: May 3, 2022 (version 1)
  5. Version of Record published: May 12, 2022 (version 2)

Copyright

© 2022, Weber et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lilian Aline Weber
  2. Sara Tomiello
  3. Dario Schöbi
  4. Katharina V. Wellstein
  5. Daniel Mueller
  6. Sandra Iglesias
  7. Klaas Enno Stephan
(2022)
Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function
eLife 11:e74835.
https://doi.org/10.7554/eLife.74835

Share this article

https://doi.org/10.7554/eLife.74835

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