mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [11C]ABP688 PET/MR-EEG

• Published in: Translational psychiatry Vol. 12; no. 1; p. 6
• Main Authors: Régio Brambilla, Cláudia, Veselinović, Tanja, Rajkumar, Ravichandran, Mauler, Jörg, Matusch, Andreas, Ruch, Andrej, Orth, Linda, Ramkiran, Shukti, Sbaihat, Hasan, Kaulen, Nicolas, Khudeish, Nibal Yahya, Wyss, Christine, Heekeren, Karsten, Kawohl, Wolfram, Rota Kops, Elena, Tellmann, Lutz, Scheins, Jürgen, Boers, Frank, Neumaier, Bernd, Ermert, Johannes, Lang, Markus, Stüsgen, Stefan, Herzog, Hans, Langen, Karl-Josef, Shah, N. Jon, Lerche, Christoph W., Neuner, Irene
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2022; Nature Publishing Group
• Subjects: 59/57; 59/78; 631/378/340; 692/53/2421; Behavioral Sciences; Biological Psychology; Brain research; Carbon Radioisotopes; Electroencephalography; Humans; Medicine; Medicine & Public Health; Mental disorders; Neurosciences; Oximes; Pharmacotherapy; Positron-Emission Tomography; Psychiatry; Psychotherapy; Pyridines; Receptor, Metabotropic Glutamate 5; Schizophrenia
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-021-01763-3

Currently, the metabotropic glutamate receptor 5 (mGluR5) is the subject of several lines of research in the context of neurology and is of high interest as a target for positron-emission tomography (PET). Here, we assessed the feasibility of using [ 11 C]ABP688, a specific antagonist radiotracer for an allosteric site on the mGluR5, to evaluate changes in glutamatergic neurotransmission through a mismatch-negativity (MMN) task as a part of a simultaneous and synchronized multimodal PET/MR-EEG study. We analyzed the effect of MMN by comparing the changes in nondisplaceable binding potential (BP ND ) prior to (baseline) and during the task in 17 healthy subjects by applying a bolus/infusion protocol. Anatomical and functional regions were analyzed. A small change in BP ND was observed in anatomical regions (posterior cingulate cortex and thalamus) and in a functional network (precuneus) after the start of the task. The effect size was quantified using Kendall’s W value and was 0.3. The motor cortex was used as a control region for the task and did not show any significant BP ND changes. There was a significant ΔBP ND between acquisition conditions. On average, the reductions in binding across the regions were - 8.6 ± 3.2% in anatomical and - 6.4 ± 0.5% in the functional network ( p  ≤ 0.001). Correlations between ΔBP ND and EEG latency for both anatomical ( p  = 0.008) and functional ( p  = 0.022) regions were found. Exploratory analyses suggest that the MMN task played a role in the glutamatergic neurotransmission, and mGluR5 may be indirectly modulated by these changes.