In-vivo whole-cortex estimation of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function, but challenging to measure in-vivo in humans. Here we present an approach to non-invasively estimate whole-cortex E/I ratio by fitting a large-scale biophysically plausible model to resting-state functional MRI (fMRI) data. We first confirm our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio is sensitive to the GABA-agonist benzodiazepine alprazolam during fMRI. Furthermore, drug-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then leverage the model to investigate the hypothesis that the E/I ratio is normatively refined during development and supports improvement in cognitive ability. We find that the E/I ratio declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio (especially in association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 years old) and Asian (7.2 to 7.9 years old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our approach opens the door to studying cortex-wide E/I ratio changes across the lifespan and in neuropsychiatric disorders.