Surface-based Tractography uncovers 'What' and 'Where' Pathways in Prefrontal Cortex

The frontal eye field (FEF) and the inferior frontal junction (IFJ) are prefrontal regions that mediate top-down functions, with mounting neuroimaging evidence suggesting that they specialize in controlling spatial versus non-spatial processing, respectively. We hypothesized that their unique patterns of structural connectivity underlie these specialized roles. To accurately infer the localization of FEF and IFJ in standard space, we performed an activation likelihood estimation meta-analysis of fMRI paradigms that reliably targeted these regions. Using surface-based probabilistic tractography methods at the individual subject level, we tracked streamlines ipsilaterally from the inferred FEF and IFJ activation peaks to the dorsal and ventral visual streams mapped on the native white matter surface parcellated using the multimodal Glasser atlas. By contrasting FEF and IFJ connectivity likelihoods, we found predominant structural connectivity from the FEF to regions of the dorsal visual stream compared to the IFJ (particularly in the left hemisphere), and conversely, predominant structural connectivity from the IFJ to regions of the ventral visual stream compared to the FEF bilaterally. Additionally, we analyzed the cortical terminations of the superior longitudinal fasciculus to the FEF and IFJ, implicating its first and third branches as segregated pathways mediating their communication to the posterior parietal cortex. The structural connectivity fingerprints of the FEF and IFJ support the view that the two visual stream architectures extend to the posterior lateral prefrontal cortex and provide converging anatomical evidence of their specialization in spatial versus non-spatial control.