Rapid homotopic communication between human orbitofrontal subregions

The orbitofrontal cortex (OFC) is a nexus for decision-making computations,¹ emotion,² and pain processing,³ with dissociable roles for its subfields: medial and anterior OFC are thought to represent economic value,^4,5,6 whereas lateral OFC receives predominantly ipsilateral sensory information^7,8 supporting stimulus-outcome associations.⁹ In areas such as primary sensorimotor cortices, homotopic interhemispheric coupling is a hallmark of cortical organization,¹⁰ but homotopy is weaker in the human prefrontal cortex,^11,12 including the OFC, where anatomy is notably heterogeneous.^13,14 Structurally, prefrontal commissural fibers course through the rostrum and genu of the corpus callosum^15,16 and the anterior commissure,¹⁷ providing a substrate for interhemispheric communication in humans. Although macaque studies have demonstrated homotopy between select OFC subregions,^18,19 whether OFC subregions communicate homotopically in humans remains unknown. Here, we use bilateral intracranial cortico-cortical evoked-potential (CCEP) mapping to show short-latency, homotopic interhemispheric connectivity across the medial/lateral axis of human OFC: the stimulation of medial OFC elicited rapid responses in contralateral medial OFC, whereas the stimulation of lateral OFC elicited rapid responses in contralateral lateral OFC. By demonstrating homotopic organization in an evolutionarily expanded, anatomically variable prefrontal territory, our data extend a canonical principle of cortical wiring into human OFC.