Cell types associated with human brain functional connectomes and their implications in psychiatric diseases

Abstract

Cell types are fundamental to the functional organization of the human brain, yet the specific cell clusters contributing to functional connectomes remain unclear. Using human whole-brain single-cell RNA sequencing data, we investigated the relationship between cortical cell cluster distribution and functional connectomes. Our analysis identified dozens of cell clusters significantly associated with resting-state network connectivity, with excitatory neurons predominantly driving positive correlations and inhibitory neurons driving negative correlations. Many of these cell clusters are also conserved in macaques. Notably, functional network connectivity is predicted by cellular communication among these clusters. We further identified cell clusters linked to various neuropsychiatric disorders, with several clusters implicated in multiple conditions. Comparative analysis of schizophrenia and autism spectrum disorder revealed distinct expression patterns, highlighting disease-specific cellular mechanisms. These findings underscore the critical role of specific cell clusters in shaping functional connectomes and their implications for neuropsychiatric diseases.