Fish, J. | Search bioRxiv

bioRxiv2024

Contrasting topologies of synchronous and asynchronous functional brain networks

We generated asynchronous functional networks (aFNs) using a novel method called optimal causation entropy (oCSE) and compared aFN topology to the correlation-based synchronous functional networks (sFNs) which are commonly used in network neuroscience studies. Functional magnetic resonance imaging (fMRI) time series from 212 participants of the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study were used to generate aFNs and sFNs. As a demonstration of how aFNs and sFNs can be used in tandem, we used multivariate mixed effects models to determine whether age interacted with node efficiency to influence connection probabilities in the two networks. After adjusting for differences in network density, aFNs had higher global efficiency but lower local efficiency than the sFNs. In the aFNs, nodes with the highest outgoing global efficiency tended to be in the brainstem and orbitofrontal cortex. aFN nodes with the highest incoming global efficiency tended to be members of the Default Mode Network (DMN) in sFNs. Age interacted with node global efficiency in aFNs and node local efficiency in sFNs to influence connection probability. We conclude that the sFN and aFN both offer information about functional brain connectivity which the other type of network does not.

neuroscience↗

bioRxiv2021

Molecular atlas of the human brain vasculature at the single-cell level

A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains poorly understood. Here, we performed single-cell RNA sequencing of 599,215 freshly isolated endothelial, perivascular and other tissue-derived cells from 47 fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We uncover extensive molecular heterogeneity of healthy fetal and adult human brains and across eight vascular-dependent CNS pathologies including brain tumors and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict numerous endothelial-to-perivascular cell ligand-receptor crosstalk including immune-related and angiogenic pathways, thereby unraveling a central role for the endothelium within brain neurovascular unit signaling networks. Our single-cell brain atlas provides insight into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

neuroscience↗