TY - JOUR TI - Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function AU - Weber, Lilian Aline AU - Tomiello, Sara AU - Schöbi, Dario AU - Wellstein, Katharina V AU - Mueller, Daniel AU - Iglesias, Sandra AU - Stephan, Klaas Enno A2 - Obleser, Jonas A2 - Büchel, Christian VL - 11 PY - 2022 DA - 2022/05/03 SP - e74835 C1 - eLife 2022;11:e74835 DO - 10.7554/eLife.74835 UR - https://doi.org/10.7554/eLife.74835 AB - 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 × 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. KW - mismatch negativity KW - acetylcholine KW - dopamine KW - NMDA receptor KW - schizophrenia KW - volatility JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -