Subregions of DLPFC display graded yet distinct structural and functional connectivity

Abstract

The human dorsolateral prefrontal cortex (DLPFC, approximately corresponding to Brodmann areas 9 and 46) has demonstrable roles in diverse executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning. However, it remains unclear whether this is the result of one functionally homogeneous region or whether there are functional subdivisions within the DLPFC. Here, we divided the DLPFC into seven areas along with rostral-caudal and dorsal-ventral axes anatomically and explored their respective patterns of structural and functional connectivity. In vivo probabilistic tractography and resting-state functional magnetic resonance imaging were employed to map out the patterns of connectivity from each DLPFC subregions. Structural connectivity demonstrated graded intra-regional connectivity within the DLPFC. The patterns of structural connectivity between the DLPFC subregions and other cortical areas revealed that he dorsal-rostral subregions was restricted to connect to other frontal and limbic areas, whereas the ventral-caudal region was widely connected to frontal, temporal, parietal, and limbic cortex. Functional connectivity analysis demonstrated that subregions of DLPFC were strongly interconnected to each other. The dorsal subregions were associated with the default mode network (DMN), while middle dorsal-rostral subregions were linked with the multiple demand network (MDN), respectively. Similar to the results of structural connectivity, the ventral-caudal subregion showed increased functional coupling with both DMN and MDN. Our results suggest that DLPFC may be subdivided by the diagonal axis of the dorsal-ventral axis and rostral-caudal axis, which support the patterns of connectivity the parts of the DLPFC reflects its integrative executive function.