Resting-State Glutamate and GABA Concentrations Predict Task-Induced Deactivation in the Default Mode Network
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Deactivation of the human brain's default mode network (DMN) is regarded as suppression of endogenous activity to support exogenous task-related processes. This phenomenon has important functional relevance and insufficient DMN deactivation has been implicated in several neuropsychiatric disorders. However, the neurochemical mechanism of the DMN′s deactivation remains largely unknown. In the present study, we test the hypothesis that the major excitatory and inhibitory neurotransmitters, glutamate and GABA, respectively, are associated with DMN deactivation. We used magnetic resonance spectroscopy to measure neurotransmitter concentrations in the posterior cingulate cortex/precuneus (PCC/PCu), a key component of the DMN, and functional magnetic resonance imaging to evaluate DMN deactivation induced by an n-back working memory task. Our results demonstrate significant associations of glutamate and GABA with DMN deactivation. Specifically, high regional GABA concentration in the PCC/PCu area is associated with enhanced deactivation induced by the task in the same region, whereas high glutamate concentration is associated with reduced deactivation. Furthermore, the association between GABA and DMN deactivation increases with the cognitive loads. These neurochemical characteristics of DMN deactivation may provide novel insights toward better understanding of the DMN′s functions under normal physiological conditions and dysfunctions in neuropsychiatric disorders.
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Alteration of glutamate/GABA equilibrium has been related to a diminished capability to focus on demanding tasks and to result in DA dysregulation, causing inhibition of defective pyramidal neurons and a decrease shift in excitation towards tasks regulated in the PFC.
“Alteration of glutamate/GABA equilibrium has been related to a diminished capability to focus on demanding tasks [98] and to result in DA dysregulation, causing inhibition of defective pyramidal neurons and a decrease shift in excitation towards tasks regulated in the PFC [99, 100].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [98]
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Experimental — accuracy not yet measuredHigher resting state GABA levels in the DMN are associated with enhanced task-induced deactivation of this network.
“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 [165]
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- Authors
- Hu, Y., Chen, X., Gu, H., & Yang, Y.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-11-20
- Volume
- 33
- Issue
- 47
- Pages
- 18566-18573
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3834059
- OpenAlex
- W2039065383
- Cited by
- 167
- References
- 62
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 9 · 2023: 15 · 2022: 13 · 2021: 17 · 2020: 18 · 2019: 18 · 2018: 13 · 2017: 13 · 2016: 12 · 2015: 14 · 2014: 3 · 2013: 1
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Siemens Medical Solutions USA
- National Institutes of Health
- National Institute on Drug Abuse
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Mind wandering and attention
- Keywords
- default mode network, glutamate, GABA, posterior cingulate cortex, precuneus, cognitive load, excitatory and inhibitory neurotransmitters, neuropsychiatric disorders
- MeSH terms
- Adult, Analysis of Variance, Brain, Brain Mapping, Female, gamma-Aminobutyric Acid, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory, Short-Term, Models, Neurological, Neural Pathways, Magnetic Resonance Spectroscopy, Oxygen, Predictive Value of Tests, Rest, Glutamic Acid
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