Excitation/inhibition balance in the aMCC influences resting state activity in the CEN

Abstract

Background: Excitation/inhibition balance can be used as a predictor not only for the functional regional response in the task-based functional magnetic resonance imaging (fMRI) but also for functional connectivity (FC) strength measured within and between networks. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns. However, the results were inconsistent and they were mainly focused on the default mode network confirming that there is a need for more robust and extensive measurements. Therefore, we investigated whole brain associations between the main excitatory - Glu - and inhibitory neurotransmitter - GABA - with the FC of the anterior mid cingulate cortex (aMCC), a node of the salience network (SN), with a particular focus on regions of the central executive network (CEN). We additionally explored how these metabolites influence basic neuronal measurements such as fractional amplitude of low frequency fluctuation (fALFF). Methods: 78 healthy subjects (39 females, age = 26.97 ± 6.53) completed a research paradigm that included a resting-state fMRI and a magnetic resonance spectroscopy (MRS) session in 7T. An MRS voxel was placed in the aMCC, and Glu, GABA and Creatine (Cr) levels were acquired using a stimulated-echo acquisition mode (STEAM) sequence. A regression analysis was conducted in SPM8 between metabolites and aMCC voxel-seed FC maps with age, sex and grey matter ratio as covariates of nuisance. Additionally, the same regression analysis was performed for fALFF. Results are reported on FWE < 0.05 cluster level significance with an initial threshold of p < 0.001, uncorrected. Results: Glu/Cr and aMCC voxel FC showed a strong negative association in the left posterior frontal gyrus and several nodes of the visual cortex. A regionally converging positive correlation was found between fALFF and GABA/Cr in the left posterior frontal gyrus. Conclusion: Both GABA and Glu levels measured in the aMCC predict the strength and the basal activity of the posterior frontal gyrus, which is a node of the CEN