title: Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network.
abstract: The balance between excitatory glutamatergic projection neurons and inhibitory GABAergic interneurons determines the function of cortical microcircuits. How these neurotransmitters relate to the functional status of an entire macro-scale network remains unknown. The posteromedial cortex (PMC) is the default mode network (DMN) node with the greatest functional connectivity; therefore, we hypothesized that PMC glutamate and GABA predict intrinsic functional connectivity (iFC) across the entire DMN. In 20 healthy men, we combined J-resolved magnetic resonance spectroscopy to measure glutamate and GABA in the PMC and resting fMRI followed by group Independent Components Analysis to extract the entire DMN. We showed that, controlling for age and partial GM volume in the MRS voxel, PMC glutamate and GABA explained about half of the variance of DMN iFC (represented by the network's beta coefficient for rest). Glutamate correlated positively and GABA correlated negatively with DMN iFC; in an alternative statistical model which included the glutamate/GABA ratio, the ratio correlated positively with DMN iFC. Age had no independent association with DMN iFC. No other network was associated with PMC glutamate or GABA. We conclude that regional neurotransmitter concentrations in a network node strongly predict network but not global brain iFC.
authors.affiliation: Clinical Research Branch, National Institute on Aging Intramural Research Program, 3001 S. Hanover St., Baltimore, MD 21225, USA. kapogiannisd@mail.nih.gov
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kapogiannis
authors.forename: David A
authors.initials: DA
authors.lastname: Reiter
authors.forename: Auriel A
authors.initials: AA
authors.lastname: Willette
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000502:physiology*; D063132:Connectome / Q000379:methods*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid