Single-subject cortical morphological brain networks: Phenotypic associations and neurobiological substrates

Although single-subject morphological brain networks provide an important way for human connectome studies, their roles and origins are poorly understood. Combining cross-sectional and repeated structural magnetic resonance imaging scans from adults, children and twins with behavioral and cognitive measures and brain-wide transcriptomic, cytoarchitectonic and chemoarchitectonic data, this study examined phenotypic associations and neurobiological substrates of single-subject morphological brain networks. We found that single-subject morphological brain networks explained inter-individual variance and predicted individual outcomes in Motor and Cognition domains, and distinguished individuals from each other. The performance can be further improved by integrating different morphological indices for network construction. Low-moderate heritability was observed for single-subject morphological brain networks with the highest heritability for sulcal depth derived networks and higher heritability for inter-module connections. Furthermore, differential roles of genetic, cytoarchitectonic and chemoarchitectonic factors were observed for single-subject morphological brain networks. Cortical thickness-derived networks were related to the three factors with contributions from genes enriched in membrane and transport related functions, genes preferentially located in supragranular and granular layers, overall thickness in the molecular layer and thickness of wall in the infragranular layers, and metabotropic glutamate receptor 5 and dopamine transporter; fractal dimension-, gyrification index-and sulcal depth-derived networks were only associated with the chemoarchitectonic factor with contributions from different sets of neurotransmitter receptors. Most results were reproducible across different parcellation schemes and datasets. Altogether, this study demonstrates phenotypic associations and neurobiological substrates of single-subject morphological brain networks, which provide intermediate endophenotypes to link molecular and cellular architecture and behavior and cognition.

Automated summary

This study investigates the phenotypic associations and neurobiological substrates of single-subject morphological brain networks using structural magnetic resonance imaging scans, behavioral and cognitive measures, and transcriptomic, cytoarchitectonic, and chemoarchitectonic data. The results show that these brain networks explain inter-individual variance, predict individual outcomes in Motor and Cognition domains, and distinguish individuals from each other. Different morphological indices can be integrated for improved network construction. The networks have low-moderate heritability, with the highest heritability for sulcal depth-derived networks and higher heritability for inter-module connections. Genetic, cytoarchitectonic, and chemoarchitectonic factors play differential roles in these networks.