Summary: Researchers developed a biologically grounded whole-brain computer model that bridges microscopic molecular chemistry with macroscopic neural activity.
The team integrated detailed empirical maps of muscarinic acetylcholine receptor density across 68 cortical regions into The Virtual Brain (TVB) simulation platform, layered upon human structural connectome data.
Key Facts
- Bridging Molecular and Whole-Brain Scales: Successfully connects microscopic receptor distribution with macroscopic, brain-wide functional activity using an open-source computational platform.
- Accounting for Receptor Heterogeneity: Incorporates region-specific maps of muscarinic acetylcholine receptors across 68 cortical areas rather than assuming uniform receptor density throughout the cortex.
- Enhanced Regional Coordination & Information Flow: Demonstrates that biologically realistic variation in receptor density significantly improves interareal functional connectivity and information routing during simulated wake and sleep states.
- Spontaneous Localized Slow Waves: Naturally replicates localized, sleep-like slow oscillations in specific cortical regions while adjacent networks remain in an awake state, modeling real-world phenomena seen in sleep deprivation and brain lesions.
- Non-Uniform Neuromodulatory Dynamics: Establishes that neuromodulators like acetylcholine exert region-specific effects determined by local receptor architecture, providing a framework for understanding disorders of consciousness and focal brain injuries.
Source: Ebrains
Researchers have developed a computer model of the human cortex that links its microscopic chemistry to its brain-wide patterns of activity, providing new evidence that regional differences in receptor density help shape how activity and information move across the brain.
The study was published in the Proceedings of the National Academy of Sciences (PNAS). It was developed using The Virtual Brain (TVB), an open-source whole-brain simulation platform that is part of the EBRAINS research infrastructure, and was supported in part through the EBRAINS 2.0 project and The Virtual Brain Twin Project.
“One of the central challenges in neuroscience is understanding how processes occurring at the molecular level influence the behaviour of the brain as a whole.”, says Leonardo Dalla Porta, researcher at the Institute of Biomedical Investigations August Pi i Sunyer (IDIBAPS) and first author of the study. “Our study provides a concrete example of how we can begin connecting these very different scales within the same computational framework.”
Most large-scale brain models simplify things by treating every cortical region as if it worked the same way. This new model takes a different approach: it incorporates detailed maps of muscarinic acetylcholine receptor density – a key target of the neuromodulator acetylcholine – across 68 brain regions, layered onto the brain’s actual structural connections.
Simulating a range of states from wakefulness to sleep, the researchers found that this biologically grounded heterogeneity increased coordination between brain regions and improved information flow compared to a model in which all regions behaved identically.
“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,” says Maria V. Sanchez-Vives, researcher at IDIBAPS and last author of the study.
The model also spontaneously reproduced a phenomenon seen in real brains: localised, sleep-like slow waves appearing in some regions while the rest of the cortex stays in an awake-like state, previously observed during attentional lapses, sleep deprivation, and around brain lesions.
The findings shed light on how molecular-level detail can meaningfully shape brain-wide activity, offering a framework the authors suggest could eventually help explain state transitions in conditions such as brain lesions or disorders of consciousness.
The work also suggests that neuromodulators such as acetylcholine do not act uniformly across the brain. Instead, their effects depend on where their receptors are concentrated, meaning the same chemical signal can produce different network dynamics in different cortical regions – a finding that, combined with the underlying structural connectivity, could help future models capture how the brain shifts between wakefulness, sleep, and altered states.
Key Questions Answered:
A: Traditional whole-brain models simplify cortical architecture by assuming all brain regions behave identically. By adding detailed empirical maps of muscarinic acetylcholine receptor density across 68 regions, this model captures how identical chemical signals produce distinct network dynamics depending on local receptor concentration, yielding far more accurate predictions of whole-brain activity.
A: Because different cortical regions possess varying densities of acetylcholine receptors, local sub-networks can transition into sleep-like slow-wave oscillations independently when neuromodulatory tone changes. The model spontaneously reproduces these isolated slow waves within an otherwise awake cortex, mimicking what happens during attentional lapses, sleep deprivation, or around structural brain lesions.
A: By linking molecular receptor profiles to whole-brain network activity, this framework can help researchers simulate and understand state transitions in conditions involving disrupted consciousness, stroke, traumatic brain injury, and neurodegenerative diseases where neuromodulatory signaling is impaired.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience research news
Author: Helen Mendes Lima
Source: EBRAINS
Contact: Helen Mendes Lima – EBRAINS
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Spatially structured heterogeneity shapes large-scale cortical dynamics in a model of the human cortex” by Leonardo Dalla Porta, Jan Fousek, Alain Destexhe, Maria V. Sanchez-Vives. PNAS
DOI:10.1073/pnas.2532072123
Abstract
Spatially structured heterogeneity shapes large-scale cortical dynamics in a model of the human cortex
Biological heterogeneity is a hallmark of brain organization, spanning molecular to anatomical scales, yet its impact on large-scale dynamics has remained largely unexplored.
Here, we integrate spatially structured regional heterogeneity derived from muscarinic receptor maps into a biophysically grounded large-scale cortical model.
We show that this structured heterogeneity enhances network synchronization and information flow, supporting more flexible and coordinated brain states. Moreover, we show that such a form of heterogeneity contributes to the emergence of localized sleep-like slow waves within an otherwise awake-like regime.
These findings demonstrate that biologically aligned intrinsic heterogeneity is an important organizing principle governing cortex-wide communication and state transitions.
