Topographic organization of the human subcortex unveiled with functional connectivity gradients

Abstract Understanding the topographic organization of the human brain remains a major goal in neuroscience. Brain atlases are fundamental to this goal, yet many contemporary human atlases cover only the cerebral cortex, leaving the subcortex a terra incognita . We revealed the complex topographic organization of the human subcortex by disambiguating smooth connectivity gradients from discrete areal boundaries in resting-state fMRI data acquired from more than 1000 healthy adults. This unveiled four scales of subcortical organization, recapitulating well-known anatomical nuclei at the coarsest scale and delineating 27 new bilateral regions at the finest. Ultra-high field strength fMRI corroborated and extended this organizational structure, enabling delineation of finer subdivisions of hippocampus and amygdala, while task-evoked fMRI revealed a subtle reorganization of subcortical topography in response to changing cognitive demands. A new subcortical atlas was delineated, personalized to account for individual connectivity differences and utilized to uncover reproducible relationships between subcortical connectivity and individual variation in human behaviors. Linking cortical networks to subcortical regions recapitulated a task-positive to task-negative organizational axis. The new atlas enables holistic connectome mapping and characterization of cortico-subcortical connectivity.