Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex

Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC (IFG pars orbitalis) functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (inferior frontal gyrus [IFG] pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with post-retrieval control. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular resolution diffusion spectrum imaging and functional connectivity analysis in un-anesthetized humans to address whether the organization of white matter connectivity differs between subregions of left VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Though several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the mid-frontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of left VLPFC support prior functional distinctions across subregions observed in task-based and functional connectivity fMRI. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general.

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