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bioRxiv · 10.1101/2025.07.10.664116

A Canonical Microcircuit for Estimating Excitation/Inhibition (E/I) Balance

Hauke, D. J.·Rodriguez-Sanchez, J.·Oloye, H.·Berndt, L. C. S.·Pinotsis, D.·Friston, K. J.·Mathalon, D. H.·Adams, R. A.
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Abstract

Excitation/inhibition (E/I) balance is crucial for maintaining healthy brain function and can be disrupted in various neurological and psychiatric disorders. Despite its importance, there are few tools to study E/I balance non-invasively in humans. Here, we propose a canonical microcircuit model to estimate E/I balance from non-invasive magneto- and electroencephalography (M/EEG) recordings by parameterising global pyramidal and inhibitory cell excitability. We first establish that E/I parameters are identifiable and recoverable. We then explore the effects of these new parameters and their interaction with other parameters in a series of simulations. To highlight the clinical relevance of this new model, we simulate changes in E/I balance and their impact on event-related potentials (ERPs) derived from paired-click, passive and active oddball paradigms, which are among the most robust clinical biomarkers of schizophrenia. Our simulations show that a loss of pyramidal cell excitability can explain reduced ERP amplitudes across all three paradigms, mirroring empirical findings in schizophrenia. This method may serve as a computational assay for estimating synaptopathy and E/I balance from non-invasive M/EEG recordings across various clinical conditions thereby advancing efforts to develop personalised interventions to restore E/I balance.

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Hauke, D. J., Rodriguez-Sanchez, J., Oloye, H., Berndt, L. C. S., Pinotsis, D., Friston, K. J., Mathalon, D. H., Adams, R. A.. 2025-07-15. A Canonical Microcircuit for Estimating Excitation/Inhibition (E/I) Balance. https://doi.org/10.1101/2025.07.10.664116

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