Regional excitation-inhibition balance predicts default-mode network deactivation via functional connectivity

&NA; Deactivation of the default mode network (DMN) is one of the most reliable observations from neuroimaging and has significant implications in development, aging, and various neuropsychiatric disorders. However, the neural mechanism underlying DMN deactivation remains elusive. As the coordination of regional neurochemical substrates and interregional neural interactions are both essential in support of brain functions, a quantitative description of how they impact DMN deactivation may provide new insights into the mechanism. Using an n‐back working memory task fMRI and magnetic resonance spectroscopy, we probed the pairwise relationship between task‐induced deactivation, interregional functional connectivity and regional excitation‐inhibition balance (evaluated by glutamate/GABA ratio) in the posterior cingulate cortex/precuneus (PCC/PCu). Task‐induced PCC/PCu deactivation correlated with its excitation‐inhibition balance and interregional functional connectivity, where participants with lower glutamate/GABA ratio, stronger intra‐DMN connections and stronger antagonistic DMN‐SN (salience network)/ECN (executive control network) inter‐network connections had greater PCC/PCu deactivation. Mediation analyses revealed that the DMN‐SN functional interactions partially mediated the relationship between task‐induced deactivation and the excitation‐inhibition balance at the PCC/PCu. The triple‐relationship discovered in the present study has the potential to bridge DMN‐deactivation related findings from various neuroimaging modalities and may provide new insights into the neural mechanism of DMN deactivation. Moreover, this finding may have significant implications for neuropsychiatric disorders related to the DMN dysfunction and suggests an integrated application of pharmacological and neuromodulation‐based strategies for rescuing DMN deactivation deficits. HighlightsInter‐/intra‐network connectivity with PCC correlated with PCC deactivation.Glutamate/GABA (Glu/GABA) ratio at PCC correlated with PCC deactivation.Glu/GABA ratio at PCC correlated with inter‐/intra‐network connectivity with PCC.PCC‐SN interaction mediated the relationship of Glu/GABA ratio and PCC deactivation.

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