Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network

The balance of excitatory and inhibitory neurotransmitters in a key brain region strongly predicts how well the brain's default mode network (DMN) communicates internally. In 20 healthy men, glutamate and GABA levels in the posteromedial cortex (a central DMN node) explained about half of the variation in the network's intrinsic functional connectivity. Glutamate correlated positively and GABA correlated negatively with DMN connectivity; the glutamate/GABA ratio also correlated positively. Age had no independent effect. No other brain network showed this relationship. The findings suggest that local neurotransmitter concentrations within a network hub can predict the functional integrity of that entire network.

Study at a glance

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.