Abstract
The default mode network (DMN) is the main large-scale network of the resting brain and the PCC/precuneus is a major hub of this network. Glutamate and GABA (γ-amino butyric acid) are the main excitatory and inhibitory neurotransmitters in the CNS, respectively. We studied glutamate and GABA concentrations in the PCC/precuneus via magnetic resonance spectroscopy (MRS) at 7T in relation to age and correlated them with functional connectivity between this region and other DMN nodes in ten healthy right-handed volunteers ranging in age between 23–68 years. Mean functional connectivity of the PCC/precuneus to the other DMN nodes and the glutamate/GABA ratio significantly correlated with age (r = 0.802, p = 0.005 and r = 0.793, p = 0.006, respectively) but not with each other. Glutamate and GABA alone did not significantly correlate with age nor with functional connectivity within the DMN. The glutamate/GABA ratio and functional connectivity of the PCC/precuneus are, therefore, independent age-related biomarkers of the DMN and may be combined in a multimodal pipeline to study DMN alterations in various disease states.
Highlights
The Default-Mode Network (DMN) is the main large-scale network of the resting brain
Kapogiannis and coworkers studied the relationship between the intrinsic functional connectivity of the DMN at 3T, which was extracted via independent component analysis of the concentrations of glutamate and γ-amino butyric acid (GABA) in the Posterior Cingulate Cortex (PCC)/precuneus in 20 healthy men
No significant correlation with age was found for the concentrations of glutamate and GABA, when we examined the ratio of glutamate to GABA concentration, it significantly correlated with age, suggesting increased excitability in older individuals, which is speculated to underly the increased prevalence of certain neurological conditions with age, such as epilepsy [40]
Summary
The Default-Mode Network (DMN) is the main large-scale network of the resting brain. It was first reported in 1997 after a series of PET studies demonstrated areas that consistently decrease their activity in various tasks in comparison with quiet repose (either with the eyes closed or with simple visual fixation) [1]. MRS quantification of glutamate and GABA at the PCC/precuneus is of interest, as a main node of the resting-state default mode network of the brain and its implication in a wide range of neurological and psychiatric disease states [11,12]. Previous studies evaluating both resting state fMRI and MRS of the DMN have yielded conflicting results. Kapogiannis and coworkers studied the relationship between the intrinsic functional connectivity of the DMN at 3T, which was extracted via independent component analysis of the concentrations of glutamate and GABA in the PCC/precuneus in 20 healthy men. We hypothesized that functional connectivity would negatively correlate with age and that this would be at least partially reflected by the declining glutamate to GABA ratio
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