Previous computational models have related spontaneous resting-state brain activity with local excitatory–inhibitory balance in neuronal populations. However, how underlying neurotransmitter kinetics associated with E–I balance govern resting-state spontaneous brain dynamics remains unknown. Understanding the mechanisms by virtue of which fluctuations in neurotransmitter concentrations, a hallmark of a variety of clinical conditions, relate to functional brain activity is of critical importance. We propose a multiscale dynamic mean field (MDMF) model—a system of coupled differential equations for capturing the synaptic gating dynamics in excitatory and inhibitory neural populations as a function of neurotransmitter kinetics. Individual brain regions are modeled as population of MDMF and are connected by realistic connection topologies estimated from diffusion tensor imaging data. First, MDMF successfully predicts resting-state functional connectivity. Second, our results show that optimal range of glutamate and GABA neurotransmitter concentrations subserve as the dynamic working point of the brain, that is, the state of heightened metastability observed in empirical blood-oxygen-level-dependent signals. Third, for predictive validity the network measures of segregation (modularity and clustering coefficient) and integration (global efficiency and characteristic path length) from existing healthy and pathological brain network studies could be captured by simulated functional connectivity from an MDMF model.

Author Summary

How changes in neurotransmitter kinetics impact the organization of large-scale neurocognitive networks is an open question in neuroscience. Here, we propose a multiscale dynamic mean field (MDMF) model that incorporates biophysically realistic kinetic parameters of receptor binding in a dynamic mean field model and captures brain dynamics from the “whole brain.” MDMF could reliably reproduce the resting-state brain functional connectivity patterns. Further employing graph theoretic methods, MDMF could qualitatively explain the idiosyncrasies of network integration and segregation measures reported by previous clinical studies.

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Competing Interests: The authors have declared that no competing interests exist.

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