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Individualized parcellation reveals functional boundaries in human prefrontal cortex

Xiang, J. D.; Zhi, D.; Arafat, B.; Nettekoven, C.; Diedrichsen, J.; Mur, M.

2026-07-06 neuroscience
10.64898/2026.07.04.736504 bioRxiv
Show abstract

Human prefrontal cortex (PFC) supports diverse higher-order cognitive functions during task execution. Increasing evidence suggests that these functions are organized along large-scale gradients, such as a rostro-caudal axis supporting progressively abstract-to-concrete information processing. At the same time, regional specialization within PFC, including focal patches selective for specific stimulus categories, suggests the presence of discrete functional boundaries. Whether PFC organization is best characterized by continuous gradients or discrete subdivisions remains unresolved. Here we show that task-evoked functional organization in PFC exhibits substantial inter-individual variability, limiting the usefulness of conventional group atlases in testing for functional boundaries. To address this challenge, we estimated individualized functional parcellations by combining a group atlas with task-evoked fMRI data spanning diverse cognitive tasks. The group atlas revealed large-scale functional gradients across PFC, whereas individualized parcellations additionally uncovered sharp functional boundaries obscured by group averaging. Moreover, functional organization in PFC was substantially more fine-grained than in other association cortices, consistent with its integrative role in cognitive control. Together, these findings suggest that PFC organization reflects an individualized mosaic of fine-grained functional subdivisions embedded within broader large-scale gradients, with important implications for defining core constructs such as the multiple-demand system.

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