Abstract
Mood disorders are associated with complex disruptions in brain networks, including those associated with the orbitofrontal cortex (OFC) and pregenual anterior cingulate cortex (pACC). Differential functions of these regions, especially the functions of the far-caudal OFC, are incompletely understood. We trained macaques to perform an approach-avoidance task and recorded cOFC and pACC neuronal activity and autonomic/somatic responses during performance, including during electrical microstimulation (EMS) of the cOFC. The cOFC was sensitive to both positive and negative stimuli, whereas the pACC was significantly more active during aversive outcomes. cOFC EMS increased avoidance, suggesting a causal cOFC function in cost-benefit decision-making. The cOFC activity led pACC activity during the decision period, supporting cOFC network prominence. Autonomic and somatic responses were positively correlated with behavioral patterns, consistent with a coordinated body-brain involvement during emotionally significant decision-making. We suggest that dysfunction of this network could potentially contribute to the etiology of mood disorders.
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Data availability
The Source Data underlying all main figures and Supplementary Figs. have been deposited in Figshare under the accession code doi: 10.6084/m9.figshare.30652049. Sample datasets used to illustrate the analysis workflow are provided in the associated GitHub repository. Other data that cannot be formatted in Excel (including large raw continuous electrophysiological and physiological recordings and related files in specialized formats that are not practical to deposit as Excel-compatible tables) are available under restricted access and may be requested by contacting the corresponding authors at: graybiel@mit.edu and georgios.k.papageorgiou@gmail.com.
Code availability
All MATLAB code used for data analyses and figure generation is available at: https://github.com/geokpap/natcomm_gp. The repository includes all scripts and a README file with instructions for reproducing the workflow using the accompanying sample datasets.
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Acknowledgements
We thank H. F. Hall, and Y. Kubota (Massachusetts Institute of Technology) for technical support, research insight, and manuscript preparation. This research was supported by the National Institute of Mental Health (P50 MH119467, to A.M.G.), the National Institute of Neurological Disorders and Stroke (R01 NS025529, to A.M.G.), the Army Research Office (W911NF-16-1-0474, to A.M.G.), the Japan Society for the Promotion of Science (JP24H02163 and JP22H04998, to K.A.), the Japan Agency for Medical Research and Development (JP24wm0625210h and JP24gm6910012h, to K.A.), the K. Lisa Yang Integrative Computational Neuroscience Center (to R.G.Y.) and the Mercatus Center at George Mason University (Emergent Ventures fellowship, to M.C.W.).
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Conceptualization, G.K.P., K.A., and A.M.G.; Methodology, G.K.P., K.A., and A.M.G.; Experimental Software, G.K.P.; Formal Analysis, G.K.P., D.J.G., K.A., M.N., and G.R.Y.; Writing—Original Draft, G.K.P.; Review, D.J.G., A.M.G., K.A., and H.N.S.; Experimental work, G.K.P., K.A., H.N.S., M.C.W., J.S., U.U., T.Y., and A.M.G.
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Papageorgiou, G.K., Amemori, Ki., Gibson, D.J. et al. Functional distinctions between orbitofrontal cortex and anterior cingulate cortex subregions in decision-making and autonomic regulation. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69447-4
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DOI: https://doi.org/10.1038/s41467-026-69447-4
