Cholinergic heterogeneity facilitates synchronization and information flow in a whole-brain model

Abstract

The human brain displays substantial regional variability in molecular, anatomical, and physiological organization. Yet, how this heterogeneity shapes large-scale neuronal dynamics remains poorly understood. To address this question, we employed a biologically informed whole-brain computational model capable of generating distinct brain states, from awake-like to sleep-like regimes. Our model was constrained by empirical human structural connectivity and spatial maps of cholinergic receptor gene expression, thereby embedding regional neuromodulatory variability into a macroscopic framework. We found that incorporating cholinergic heterogeneity had a significant impact on brain dynamics: it not only facilitated network synchronization but also enhanced information flow between brain regions. Furthermore, we addressed a particularly intricate dynamic regime characterized by the coexistence of localized sleep-like activity within otherwise awake-like states. We showed that the emergence of these slow waves was a byproduct of both regional levels of neuronal adaptation and structural connectivity. In summary, our findings highlight the critical role of molecular and anatomical heterogeneity in shaping global brain dynamics, suggesting new avenues for linking microscale diversity to macroscale function.