The Structural and Functional Connectivity of the Orbitofrontal Cortex: Deconvoluting Brodmann Areas 11, 13, 14, and...

The orbitofrontal cortex is central to decision making, reward valuation, emotional regulation, and goal-directed behavior. Although traditional cytoarchitectonic classifications, such as Brodmann map, identified multiple cortical areas within the orbitofrontal cortex, recent neuroimaging advancements such as the Human Connectome Project have refined our anatomical understanding in granular detail. This study characterizes the structural and functional connectivity of key orbitofrontal subregions, particularly Brodmann area 11, Brodmann area 13, Brodmann area 14, and Brodmann area 47, corresponding to Human Connectome Project areas 11L, 13L, orbitofrontal cortex (OFC)/polar orbitofrontal cortex, and 47m/47 s/a47r, respectively. Structural connectivity analyses reveal significant large white matter connections with the inferior frontal-occipital fasciculus, uncinate fasciculus, and pathways linking the OFC to the amygdala and temporal cortex. Functionally, 11L is involved in valuation and decision making, 13L contributes to emotion regulation, OFC/polar orbitofrontal cortex plays a key role in reward processing and self-referential cognition, and areas 47 m, 47 s, and a47r have a role in coordinating cognitive and emotional information, as well as language production and semantic processing. These subregions integrate sensory-affective information and support theory of mind and semantic processing. Disruptions in OFC connectivity contribute to neuropsychiatric and neurodegenerative disorders, inducing various symptoms of addiction, obesity, depression, Parkinson disease, and frontotemporal dementia, highlighting the relevance of our improved anatomical understanding of this region for targeted neuromodulation strategies. Importantly, this work leverages an anatomically precise nomenclature from the Human Connectome Project to refine our understanding of the OFC's connectivity, enabling more precise neuromodulatory targeting while improving the reproducibility and sharing of research findings of this region.