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

Area of Science:

• Neuroscience
• Radiochemistry
• Neuroimaging

Background:

• Metabotropic glutamate receptor 5 (mGluR5) is a key target in neurological research.
• Positron-emission tomography (PET) is a valuable tool for in vivo imaging of neuroreceptors.
• Understanding glutamatergic neurotransmission changes is crucial for neurological disorders.

Purpose of the Study:

• To evaluate the feasibility of using [11C]ABP688 PET to measure changes in mGluR5 availability during a mismatch negativity (MMN) task.
• To investigate the relationship between mGluR5 binding potential and EEG measures during auditory oddball paradigms.
• To explore the role of mGluR5 in glutamatergic neurotransmission modulated by cognitive tasks.

Main Methods:

• Simultaneous multimodal PET/MR-EEG acquisition in 17 healthy subjects.
• Utilized [11C]ABP688, a specific mGluR5 antagonist radiotracer.
• Analyzed nondisplaceable binding potential (BPND) changes using a bolus/infusion protocol before and during the MMN task.

Main Results:

• A significant reduction in mGluR5 BPND was observed in anatomical (posterior cingulate cortex, thalamus) and functional (precuneus) regions during the MMN task.
• Reductions averaged -8.6% in anatomical and -6.4% in functional networks (p ≤ 0.001).
• Correlations found between BPND changes and EEG latency, suggesting a link between glutamatergic neurotransmission and neural processing.

Conclusions:

• The MMN task induces measurable changes in mGluR5 availability, supporting its use in studying glutamatergic neurotransmission.
• [11C]ABP688 PET is feasible for assessing task-induced modulations of mGluR5.
• Findings suggest mGluR5 is indirectly modulated by glutamatergic changes during the MMN task.