Tools for next generation cortical cartography: atlas, individual variability, evolutionary lineages, and connectivity of human cortical areas.

This proposal aims to undertake a next-generation cortical cartography effort by generating a more accurate multi-modal atlas of human cortical areas, studying the individual variability of these cortical areas and their evolutionary lineages, validating and refining non-invasive methods of cortical connectivity, and enhancing our widely used software tools specially designed for cortical analysis. Much new data is now available for improving our highly impactful multi-modal atlas of human cortical areas published in 2016, including higher resolution and different fMRI scans, higher resolution and better architectural measures, and non-MRI-based measures like spatial transcriptomics which assess both gene expression patterns and cell type distributions in cerebral cortex. Additionally, individual variability and subareal organization of these cortical areas have not been well charac- terized; however, understanding these aspects is critical for the new atlas to have maximal clinical impact, as demonstrated by our recent highly successful clinical-translational applications of the current atlas. Another ma- jor objective is to better understand the evolution of human cortical areas relative to intensively studied macaque and marmoset monkeys by identifying areas common to all 3 species and areas found only in the human lineage. This will enable better translation of Non-Human Primate (NHP) invasive experiments to humans. NHPs also enable quantitative neuroanatomical measures of brain connectivity, providing an invaluable gold standard for validating noninvasive MRI-based methods for estimating cortical connectivity that are widely used in humans. Identifying the best-performing methods in NHPs will accelerate progress in developing more accurate non- invasive connectivity methods for humans. Finally, our widely used tools for multi-modal cortical visualization (Connectome Workbench), data sharing (BALSA neuroimaging study results repository), and analysis (the CIFTI file format and standard space that enables precise combined cortical and subcortical analysis) must both be maintained and extended in multiple ways to enable the new datatypes to be best combined with existing data. Altogether, this project has five key deliverables. (1) A version 2.0 of our atlas of human cortical areas, including elucidation of their subareal organization. (2) Characterizing the individual variability of human cortical areas, including their size, shape, and position and whether all humans have the same set of areas or whether some are missing areas and others have extra areas. (3) Identifying which cortical areas have homologues in NHPs and which are human specific. (4) A critical evaluation in macaques of the non-invasive measures of functional and structural connectivity that are widely used in humans to determine which methods perform best at replicat- ing invasive connectivity in the macaque and then producing human cortical connectomes using the best meth- ods. (5) Improvements to our widely used tools for cortical visualization, data sharing, and analysis. Completing these aims will accelerate progress towards understanding the cerebral cortex and enable more rapid translation of basic science insights and neuroanatomical maps to clinical practice for diseases involving the cerebral cortex. Project Number: 1R01NS144453-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Matthew Glasser (+1 co-PI) | Institution: WASHINGTON UNIVERSITY, SAINT LOUIS, MO | Award Amount: $618,077 | Activity Code: R01 | Study Section: Imaging Technology for Neuroscience Study Section[ITN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11366222