Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling

Background: The balance of excitation and inhibition (E-I) is a key functional property of cortical microcircuits [1] which changes through lifespan. Adolescence is considered a crucial period for the maturation of E-I balance [2,3]. This has been primarily observed in animal studies, and human in vivo evidence on adolescent maturation of the E-I balance at an individual level is limited. Here, we investigated an in vivo marker of regional E-I balance in human adolescents based on individualized biophysical network models. Methods: Regional E-I balance was estimated using large-scale simulations of individualized biophysical network models [4] fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts (Figure 1a). We next investigated the effect of age on these estimates. Following, we studied the embedding of the spatial neurodevelopmental pattern of E-I across different domains of cortical organization as well as meta-analytic maps of cortical function and developmental transcriptomics. In addition, we assessed the robustness of excitation-inhibition balance estimate and its age-related changes to the effects of inter-individual variability of SC, modeling configurations, and the randomness within the optimizer and simulations. Lastly, we contrasted our marker of the E-I balance to alternative previously used simulation-based markers. Results: We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation or lack of change in sensorimotor areas in both datasets (Figure 1b). This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation in cortical organization. Spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Last, we illustrated how different simulation-based markers of excitation-inhibition balance show differential sensitivity to maturational change, and highlighted a potential redundancy of model parameters. Conclusion: Our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.