Large-Scale Network Embedding Predicts Opposing Functions of Adjacent Regions Within Human Prefrontal Cortex

Prefrontal regions are hypothesized to be organized hierarchically in support of cognitive control. Using precision functional MRI in three independent cohorts of intensively scanned participants (N=37), we consistently identified a lateral prefrontal cortex (LPFC) region linked to a canonical control network separate from a nearby rostral LPFC region linked to the action-mode network. Despite their spatial juxtaposition, the two regions were differentially coupled to the caudate and ventral putamen, suggesting they are components of segregated networks. Working memory demands activated the canonical LPFC control region but not the adjacent region. Contrasting go and no-go trials during target detection revealed a robust functional double dissociation during goal-directed behavior. The canonical LPFC control region activated when responses were withheld, while the putamen-coupled LPFC region increased activity during executed responses. These findings demonstrate that adjacent LPFC regions participate in opposing functions predicted by their embedding within distinct parallel large-scale networks.