A multi-frequency whole-brain neural mass model with homeostatic feedback inhibition

Whole-brain models are valuable tools for understanding brain dynamics in health and disease by enabling the testing of causal mechanisms and identification of therapeutic targets through dynamic simulations. Among these models, biophysically inspired neural mass models have been widely used to simulate electrophysiological recordings, such as MEG and EEG. However, traditional models face limitations, including susceptibility to hyperexcitation, which constrains their ability to capture the full richness of neural dynamics. Here, we developed and characterized a new version of the Jansen-Rit neural mass model aimed at overcoming these limitations. Our model incorporates inhibitory synaptic plasticity (ISP), which adjusts inhibitory feedback onto pyramidal neurons to clamp their firing rates around a target value. Further, the model combined two subpopulations of neural cortical columns oscillating in α and γ, respectively, to generate a richer EEG power spectrum. We analyzed how different model parameters modulate oscillatory frequency and connectivity. We considered a model's showcase, simultaneously fitting EEG and fMRI recordings during NREM sleep. Bifurcation analysis showed that ISP increases the parameters' range in which the model exhibited sustained oscillations; the target firing rate acts as a bifurcation parameter, moving the system across the bifurcation point, producing different oscillatory regimes, from slower to faster. High frequency activity emerged from low global coupling, high firing rates, and a high proportion of γ versus α subpopulations. Importantly, ISP was necessary in the multi-frequency model to successfully fit EEG functional connectivity across frequency bands. Finally, ISP-controlled reductions in excitability reproduced both the slow-wave activity and the reduced connectivity in NREM sleep. Altogether, our model is compatible with biological evidence of the effects of E/I balance on modulating brain rhythms and connectivity, as observed in sleep, neurodegeneration, and chemical neuromodulation. This biophysical model with ISP provides a springboard for realistic brain simulations in health and disease.