Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function
- University of Zurich, Switzerland
- 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.
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Data from: Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor functionETH Research Collection, doi:10.3929/ethz-b-000477685.
Article and author information
Author details
Lilian Aline Weber
Klaas Enno Stephan
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).
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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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
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