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 [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. We analyzed the effect of MMN 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. Anatomical and functional regions were analyzed. 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 0.3. The motor cortex was used as a control region for the task and did not show any significant BPND changes. There was a significant ΔBPND 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 ΔBPND 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.

The growing demand for precise and reliable biomarkers in psychiatry is fueling research interest in the hope that identifying quantifiable indicators will improve diagnoses and treatment planning across a range of mental health conditions. The individual properties of brain networks at rest have been highlighted as a possible source for such biomarkers, with the added advantage that they are relatively straightforward to obtain. However, an important prerequisite for their consideration is their reproducibility. While the reliability of resting-state (RS) measurements has often been studied at standard field strengths, they have rarely been investigated using ultrahigh-field (UHF) magnetic resonance imaging (MRI) systems. We investigated the intersession stability of four functional MRI RS parameters-amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; representing the spontaneous brain activity), regional homogeneity (ReHo; measure of local connectivity), and degree centrality (DC; measure of long-range connectivity)-in three RS networks, previously shown to play an important role in several psychiatric diseasesthe default mode network (DMN), the central executive network (CEN), and the salience network (SN). Our investigation at individual subject space revealed a strong stability for ALFF, ReHo, and DC in all three networks, and a moderate level of stability in fALFF. Furthermore, the internetwork connectivity between each network pair was strongly stable between CEN/SN and moderately stable between DMN/SN and DMN/SN. The high degree of reliability and reproducibility in capturing the properties of the three major RS networks by means of UHF-MRI points to its applicability as a potentially useful tool in the search for disease-relevant biomarkers.Tanja Veselinovi c and Irene Neuner equally contributed to this study.