Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function
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.
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.
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
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.
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).
- Jonas Obleser, University of Lübeck, Germany
- Preprint posted: March 20, 2021 (view preprint)
- Received: October 25, 2021
- Accepted: April 26, 2022
- Accepted Manuscript published: May 3, 2022 (version 1)
- Version of Record published: May 12, 2022 (version 2)
© 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.
- Page views
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Sensory neurons previously shown to optimize speed and balance in fish by providing information about the curvature of the spine show similar morphology and connectivity in mice.
Beta oscillations in human sensorimotor cortex are hallmark signatures of healthy and pathological movement. In single trials, beta oscillations include bursts of intermittent, transient periods of high-power activity. These burst events have been linked to a range of sensory and motor processes, but their precise spatial, spectral, and temporal structure remains unclear. Specifically, a role for beta burst activity in information coding and communication suggests spatiotemporal patterns, or travelling wave activity, along specific anatomical gradients. We here show in human magnetoencephalography recordings that burst activity in sensorimotor cortex occurs in planar spatiotemporal wave-like patterns that dominate along two axes either parallel or perpendicular to the central sulcus. Moreover, we find that the two propagation directions are characterised by distinct anatomical and physiological features. Finally, our results suggest that sensorimotor beta bursts occurring before and after a movement can be distinguished by their anatomical, spectral and spatiotemporal characteristics, indicating distinct functional roles.