Researchers have developed a computer model of the human cortex that connects its microscopic chemistry to brain-wide patterns of activity, according to an Aug. 7 study published in the Proceedings of the National Academy of Sciences. The new model provides evidence that regional differences in receptor density help shape how activity and information move across the brain.
The research team used The Virtual Brain, an open-source whole-brain simulation platform that is part of the EBRAINS research infrastructure. The project received support from both the EBRAINS 2.0 project and The Virtual Brain Twin Project.
Unlike most large-scale brain models, which treat every cortical region as functioning identically, this new approach incorporates detailed maps of muscarinic acetylcholine receptor density across 68 brain regions layered onto actual structural connections within the brain. Simulating states ranging from wakefulness to sleep, researchers found that biologically grounded heterogeneity increased coordination between regions and improved information flow compared to models where all regions behaved alike.
"Whole-brain models offer systems neuroscientists deep insight into the global impact of local phenomena, giving us a better understanding of mechanisms and generating testable predictions. This study is an example of the impact of interareal heterogeneity on how global and local brain states are generated," said Maria V. Sanchez-Vives, researcher at IDIBAPS and last author of the study.
The model also spontaneously reproduced a phenomenon observed in real brains: localized sleep-like slow waves appearing in some regions while other parts remained in an awake-like state—a pattern previously seen during attentional lapses, sleep deprivation, and around brain lesions. According to the authors, these findings provide a framework for understanding how molecular-level detail can influence broad patterns of neural activity and may eventually help explain state transitions in conditions such as brain lesions or disorders of consciousness.
The work further suggests that neuromodulators like acetylcholine do not act uniformly throughout the cortex; instead, their effects depend on where their receptors are concentrated. This means identical chemical signals can produce different network dynamics depending on cortical region—an insight researchers say could help future models better capture shifts between wakefulness, sleep, and altered states.
