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Data Acquisition and Analysis In Brainstem Evoked Response Audiometry In Mice
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Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine

Lilian Aline Weber1, Sara Tomiello1, Dario Schöbi1

  • 1Translational Neuromodeling Unit, Institute for Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland.

Elife
|May 3, 2022
PubMed

Insights

Auditory mismatch negativity (MMN) responses in schizophrenia are differentially affected by cholinergic and dopaminergic systems. Biperiden, an acetylcholine antagonist, altered MMN, while amisulpride, a dopamine antagonist, did not, suggesting potential for personalized treatment prediction.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Auditory mismatch negativity (MMN) is a potential biomarker for NMDA receptor (NMDAR) dysfunction in schizophrenia.
  • Aberrant neuromodulator interactions with NMDARs may contribute to schizophrenia's clinical heterogeneity.

Purpose of the Study:

  • To investigate if auditory mismatch responses are sensitive to cholinergic and dopaminergic function modulation in schizophrenia.
  • To explore the differential effects of receptor antagonists and agonists on MMN under varying environmental stability.

Main Methods:

  • Two double-blind, placebo-controlled studies with 81 participants each.
  • Systematic testing of auditory mismatch responses with biperiden (muscarinic antagonist) and amisulpride (dopamine antagonist).
  • Assessment of galantamine (cholinergic enhancer) and levodopa (dopaminergic enhancer) effects on MMN.

Main Results:

  • A significant drug × mismatch interaction was observed.
  • Biperiden delayed and shifted MMN, especially in high environmental stability, unlike amisulpride.
  • Galantamine and levodopa did not significantly affect MMN.

Conclusions:

  • MMN shows differential sensitivity to muscarinic versus dopaminergic receptor modulation in schizophrenia.
  • These findings may aid in developing predictive tests for individual treatment responses in schizophrenia.
Keywords:
NMDA receptoracetylcholinedopaminehumanmismatch negativityneuroscienceschizophreniavolatility

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