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Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network
Open accessAbstract
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.
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“Higher resting state GABA levels in the DMN are associated with enhanced task-induced deactivation of this network [165–167]”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [166]
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Metadata
- Authors
- Kapogiannis, D., Reiter, D. A., Willette, A. A., & Mattson, M. P.
- Affiliations
- National Institute on Aging (US)
- Corresponding author
- Kapogiannis, Dimitrios
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 64
- Pages
- 112-119
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3801193
- OpenAlex
- W1971032414
- Cited by
- 211
- References
- 67
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 12 · 2023: 15 · 2022: 15 · 2021: 23 · 2020: 19 · 2019: 17 · 2018: 18 · 2017: 19 · 2016: 14 · 2015: 11 · 2014: 18 · 2013: 4
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- posteromedial cortex, default mode network, intrinsic functional connectivity, glutamate, GABA, glutamate/GABA ratio, neurotransmitter concentrations, cortical microcircuits, excitation-inhibition balance, resting-state functional connectivity, age effects
- MeSH terms
- Brain Mapping, Cerebral Cortex, gamma-Aminobutyric Acid, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Neural Pathways, Magnetic Resonance Spectroscopy, Tissue Distribution, Neurotransmitter Agents, Glutamic Acid, Connectome
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