Abstract
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 У-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.
Highlights
The human brain responds to both low and high demand cognitive tasks by changing its activity patterns across the brain
In this multi-modal MRI study, we applied magnetic resonance spectroscopy and functional MRI to investigate the role of Gamma-aminobutyric acid (GABA) in the salience network (SN) on RS network connectivity, by assessing the relationship between individual differences in SN GABA levels and RS connectivity (1) within the SN and (2) across default-mode network (DMN) and central executive network (CEN) networks, and (3) how GABA impacts the role of the SN as a communication hub within the triple network
The present study investigated the relation between GABA and Glx levels in the dorsal anterior cingulate cortex (dACC), a core region of the SN, and individual differences in resting-state connectivity within the SN, and across the DMN and CEN in a group of healthy male participants
Summary
The human brain responds to both low and high demand cognitive tasks by changing its activity patterns across the brain. Task-based neuroimaging studies have highlighted the complexity of GABA-BOLD associations depending on task content and cognitive demand[3,4,5,19,20], which might suggest a complex and differential role of GABA across and between networks during rest In this multi-modal MRI study, we applied magnetic resonance spectroscopy and functional MRI to investigate the role of GABA in the SN on RS network connectivity, by assessing the relationship between individual differences in SN GABA levels and RS connectivity (1) within the SN and (2) across DMN and CEN networks, and (3) how GABA impacts the role of the SN as a communication hub within the triple network. We further hypothesized opposing directionalities of dACC GABA and network intraconnectivity of the DMN and CEN, and expected GABA to be associated with the interconnectivity between networks
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