Proteomic insights into the macaque insular parcellation based on structural connectivity gradients

Abstract Gradients across microstructure, macro-connectivity, and gene expression scales have been identified in the primate brain, offering a continuous perspective to explore regional heterogeneity. The macaque insula, with its extensive connections with other cortical regions and involvement in diverse functions, exhibits gradient transitions at the microstructural level. However, the gradients of macroscopic structural connectivity (SC) and its relationship with gene expression in the macaque insula remain unclear. We hypothesized that SC gradients are closely associated with gene expression, driving insular parcellation. To test this, we analyzed high-resolution diffusion-weighted MR imaging alongside spatially aligned proteomic data. Our findings revealed a rostrocaudal organization of the dominant SC gradient in the macaque insula, leading to the identification of a four-subregion pattern within the insula based on the first two SC gradients. Proteomic profiles strongly correlated with the dominant SC gradient and the clustering of proteomic similarity aligned with the four-subregion pattern. Notably, the dominant SC gradient more effectively captured spatial protein expression variations than T1w/T2w and cortical thickness maps. Overall, this study demonstrated that the SC gradient analysis revealed a four-subregion pattern of parcellation aligned with the spatial distribution of proteomic profiles along the rostro-caudal axis.