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

Abstract

Introduction: 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 [1]. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns [2,3]. 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 fluctuations (fALFF). Methods: 106 subjects (age = 27.09 ± 6.72, 44 females) 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. Conclusions: 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