Anterior cingulate GABA and glutamate concentrations are associated with resting-state network connectivity

In recent years, resting-state (RS) networks and RS function have received increased attention, highlighting their importance in both cognitive function and psychopathology. The neurochemical substrates underlying RS networks and their interactions, however, have not yet been well established. Even though prior research has provided first evidence for a negative association between brain GABA levels and RS connectivity, these findings have been limited to within network connectivity, and not network interactions. In this multi-modal imaging study, we investigated the role of the main inhibitory neurotransmitter Y-aminobutyric acid (GABA) and the main excitatory neurotransmitter glutamate (Glx) on RS network function and network coupling of three core networks: the default-mode network (DMN), salience network (SN), and central executive network (CEN). Resting-state functional connectivity and GABA and Glx levels in the dorsal anterior cingulate cortex (dACC) were assessed in 64 healthy male participants using functional MRI and magnetic resonance spectroscopy (MRS). Analyses showed that dACC GABA levels were positively correlated with resting-state connectivity in the CEN, and negatively associated with functional coupling of the DMN and CEN. In contrast, GABA/Glx ratios were inversely correlated with the SN and DMN. These findings extend insights into the role of GABA and Glx in individual networks to interactions across networks, suggesting that GABA levels in the SN might play a role in RS functional connectivity within the central executive network, and network interactions with the default-mode network. Our results further suggest a potentially critical role of the relationship between GABA and Glx in RS network function.