Topographic organization of the human subcortex unveiled with functional connectivity gradients

Brain atlases are fundamental to understanding the topographic organization of the human brain, yet many contemporary human atlases cover only the cerebral cortex, leaving the subcortex a terra incognita. We use functional MRI (fMRI) to map the complex topographic organization of the human subcortex, revealing large-scale connectivity gradients and new areal boundaries. We unveil four scales of subcortical organization that recapitulate well-known anatomical nuclei at the coarsest scale and delineate 27 new bilateral regions at the finest. Ultrahigh field strength fMRI corroborates and extends this organizational structure, enabling the delineation of finer subdivisions of the hippocampus and the amygdala, while task-evoked fMRI reveals a subtle subcortical reorganization in response to changing cognitive demands. A new subcortical atlas is delineated, personalized to represent individual differences and used to uncover reproducible brain–behavior relationships. Linking cortical networks to subcortical regions recapitulates a task-positive to task-negative axis. This new atlas enables holistic connectome mapping and characterization of cortico–subcortical connectivity. This work by Tian and colleagues unveils the extraordinarily complex layout of the human subcortex by identifying 27 new functional regions that organize hierarchically across four scales and adapt to changing cognitive demands.