Dynamic mechanisms underlying neurotransmitter-regulated brain excitation-inhibition balance: insights from the MDMF...

Excitation-inhibition (E-I) imbalance is a core pathological mechanism underlying many psychiatric disorders. In this study, we integrate structural and functional magnetic resonance imaging data to construct a large-scale brain network model, aiming to investigate how perturbed structural connectivity drive brain network reorganization and how neurotransmitters regulate E-I balance. The results show that the multiscale dynamic mean-field (MDMF) model identifies steady-state regimes of neurotransmitter-related parameters that yield relatively high correspondence between simulated and empirical resting-state functional connectivity. Furthermore, synaptic pathology is simulated by altering structural connectivity, and the resulting functional connectivity reproduces network topological features observed in neurological and psychiatric disorders. Finally, the E-I ratio is quantified at both the neurotransmitter level and the neuronal firing-rate level. By modulating inhibitory neurotransmitter-related parameters, selected topological properties of the simulated FC networks shift closer to the empirical condition. These findings establish a link between E-I imbalance, neurotransmitter regulation, and structural abnormalities, providing new insights into the pathogenesis and potential treatment strategies for psychiatric disorders.