Spatio-molecular gene expression reflects dorsal anterior cingulate cortex structure and function in the human brain

The human brain’s dorsal anterior cingulate cortex (dACC) is critical in cognitive control, specifically reward processing and conflict monitoring, and regulates fear and pain expression. The dACC is evolutionarily older than more recently specialized neocortical areas, such as the dorsolateral prefrontal cortex (dlPFC). Its evolutionary specializations, including agranularity and presence of von Economo neurons (VENs) are linked to its unique roles in cognitive and emotional processing. We generated paired spatially resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) data in ten adult neurotypical donors to define cell types and spatial domains. We used non-negative matrix factorization to project gene expression patterns from the snRNA-seq data onto the SRT data to infer spatial localization. Utilizing publicly available resources, we explored spatial topography, enrichment of disease risk, and connectivity of spatially localized cell types, including VENs. Leveraging dlPFC snRNA-seq and SRT data from the same donors, we compared laminar and molecular specialization between the regions.