The connectivity fingerprints of prefrontal cortex indicate separate ‘What’ and ‘Where’ pathways for governing top-down attentional control

It has been shown that two structures within the prefrontal cortex, namely the frontal eye field (FEF) and inferior frontal junction (IFJ), encode spatial versus non-spatial (such as feature- or object-based) representations, respectively. But it remains uncertain whether this distinct functional segregation is also reflected in the underlying anatomical and functional connectivity patterns of these two structures. Here, we hypothesized that FEF is predominantly connected with spatiotopically organised regions in the dorsal ('where') visual stream, whereas IFJ has predominant connectivity with the ventral ('what') visual stream. In order to test this hypothesis, we compared the anatomical and functional connectivity patterns of FEF and IFJ, combining (1) fMRI BOLD co-activation analyses, (2) probabilistic diffusion tractography (DTI), and (3) frequency-resolved MEG connectivity measures on the same subjects from the Human Connectome Project. Upon accurately inferring the localization of these regions in stereotaxic space using activation likelihood estimation (ALE), meta-analytic connectivity modeling (MACM) revealed differential coactivations in frontal, parietal and temporal cortices, consistent with our hypothesis. Further, we investigated the surface-based probabilistic tractography using 3T diffusion MRI data, tracking streamlines to the dorsal and ventral visual streams. We found preferential white matter connectivity between FEF and the visual dorsal stream, and between IFJ and the visual ventral stream. Finally, we tested for the functional coupling of FEF/IFJ with the dorsal versus ventral stream in the visual cortex, applying seed-based functional connectivity analyses to temporally high-resolving resting-state magnetoencephalography (MEG) recordings in various frequency bands. Here, FEF has predominant power- and phase-coupling with the superior parietal lobe in the beta band, while IFJa has predominant power- and phase-coupling with the middle and inferior temporal cortex in delta and gamma oscillations. We conclude that both the anatomical and functional connectivity fingerprints of FEF and IFJ are congruent with each brain region's function. The contrasting connectivity patterns of FEF and IFJ not only align with their respective functional roles in spatial vs. non-spatial top-down attention but also suggest the existence of a dorsal versus ventral path within the prefrontal cortex.