Next Generation Multi-modal Human Connectome Project Atlases - This project will develop three new multi-modal atlases based on high resolution Human Connectome Project (HCP) data and its precise methods. 1) The project will create a new data-driven atlas of spatially overlapping weighted grey-matter functional networks, side-stepping current limitations in non-weighted, non-overlapping atlases of functional networks and compare to the prior literature. 2) The project will create a new data-driven atlas of white matter tracts and their corresponding grey matter projection territories and compare these results to traditional ROI-based atlases, which may have biases or have missed tracts. 3) The project will complete the semi-automated multi-modal atlas of human brain areas, building upon the HCP’s prior map of 180 neocortical brain areas per cerebral hemisphere to include the non-neocortical brain areas using surface-based and volume- based methods as appropriate with extensive comparison to the prior neuroanatomical literature. The end result of successful completion of this project will be complete, integrated atlases of human grey matter brain areas, functional networks, and white matter tracts, which will have intrinsic value, e.g., for neurosurgical planning. These atlases and the automated methods for regenerating them in new subjects will enable measuring multi- modal imaging derived phenotypes (IDPs) for HCP-Style neuroimaging data across the whole brain. By collaps- ing non-independent statistical tests within neuroanatomically well-defined brain structures and averaging out random noise, such IDPs will have improved statistical sensitivity and power. This generically useful approach has the most promise for creating interpretable imaging biomarkers useful for elucidating the mechanisms behind both healthy brain aging and Alzheimer’s Disease (AD) and Alzheimer’s Disease Related Dementias (ADRD). Each aim of the project will have a technology development sub-aim (part a) to develop or improve upon the needed methods for generating that aim’s atlas. Then the atlas will be created using data from the young adult HCP (part b) and the findings will be integrated across the 3 aims (i.e., direct comparison and cross-annotation between the atlases of brain areas, grey matter functional networks, and white matter tracts). Finally, we will produce automated pipelines to regenerate the atlases in the data of the HCP Aging project, the Adult Aging Brain Connectome (AABC) project, and the Alzheimer’s Disease (AD) and Alzheimer’s Disease Related Demen- tias (ADRD) Connectomes Related to Human Disease (CRHD) projects, to disaggregate the data by sex, and to generate multi-modal IDPs based on these atlases, pipelines that external investigators can also use in their own studies. These atlases and IDPs will then feed into five ongoing projects studying Alzheimer’s Disease (AD) and Alzheimer’s Disease Related Dementias (ADRD), four that are subprojects of the AABC and an R01 that is working on the AD/ADRD CRHD data. Overall, the proposal will address three key gaps in the current HCP atlases and IDP generation pipelines to accelerate innovation and discovery in the neuroimaging field.
