Transcriptomic and Macroscopic Architectures of Multimodal Covariance Network Reveal Molecular–Structural–Functional Co-alterations

Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions.Owing to lacking an effective approach to quantifying the covarying of structure and functional responses,how the structural–functional circuits interact and how genes encode the relationships,to deepen our knowledge of human cognition and disease,are still unclear.Here,we propose a multimodal covariance network(MCN)construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual.We further explored the potential association between brain-wide gene expression patterns and structural–functional covarying in individuals involved in a gambling task and individuals with major depression disorder(MDD),adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts.MCN analysis showed a replicable cortical structural–functional fine map in healthy individuals,and the expression of cognition-and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences.Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences.