mGluR5 binding changes during a mismatch negativity task in PET/MR-EEG
10th January 2022
Cláudia Régio Brambilla,Tanja Veselinović, Ravichandran Rajkumar, Jörg Mauler, Andreas Matusch, Andrej Ruch, Linda Orth, Shukti Ramkiran, Hasan Sbaihat, Nicolas Kaulen, Nibal Yahya Khudeish, Christine Wyss, Karsten Heekeren, Wolfram Kawohl, Elena Rota Kops, Lutz Tellmann, Jürgen Scheins, Frank Boers, Bernd Neumaier, Johannes Ermert, Markus Lang, Stefan Stüsgen, Hans Herzog, Karl-Josef Langen, N. Jon Shah, Christoph W. Lerche and Irene Neuner
Glutamate is a chemical used by nerve cells to send signals to other cells and is generally acknowledged as the most important excitatory neurotransmitter for normal brain function. This is supported by an increasing number of studies that have confirmed abnormal glutamatergic neurotransmission in several mental disorders, such as schizophrenia, depression, mood disorders, sleep deprivation, and addiction. As a result, interventions targeting the glutamate system are currently under development.
In this context, the metabotropic glutamate receptor 5 (mGluR5) is the subject of several lines of research and is of great interest as a target for positron-emission tomography (PET).
The focus of this particular study was on the feasibility of using [11C]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.
The effect of MMN was assessed by comparing the changes in nondisplaceable binding potential (BPND) prior to (baseline) and during the task in 17 healthy subjects by applying a bolus/infusion protocol. Both anatomical and functional regions were analysed, and a small change in BPND 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 found to be 0.3. The motor cortex was used as a control region for the task and did not show any significant BPND changes.
These exploratory analyses provide evidence of a reduction in glutamatergic receptor binding during an MMN task and indirectly show an active alteration in glutamatergic neurotransmission during auditory information processing in healthy subjects for the first time. In light of this, further replication is planned, along with investigations into whether the extent of the changes recorded is related to cognitive abilities, or in the case of patients, whether there is a correlation with clinical symptomatology. Thus, the approach may be applied to further investigate the role of glutamatergic neurotransmission in healthy subjects and in patients with various mental disorders.
Origional publication: mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [11C]ABP688 PET/MR-EEG