Functional distinctions between orbitofrontal cortex and anterior cingulate cortex subregions in decision-making and
Georgios K Papageorgiou1,2, Ken-Ichi Amemori3, Daniel J Gibson4,5
1McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA. georgios.k.papageorgiou@gmail.com.
Nature Communications
|February 14, 2026
Summary
This study reveals the orbitofrontal cortex (OFC) plays a key role in cost-benefit decisions, influencing mood disorder development. Electrical stimulation of the OFC increased avoidance behavior in macaques.
Area of Science:
- Neuroscience
- Decision-making research
- Mood disorder research
Background:
- Mood disorders involve complex brain network disruptions, particularly in the orbitofrontal cortex (OFC) and pregenual anterior cingulate cortex (pACC).
- The precise functions of these regions, especially the caudal OFC, remain unclear.
- Understanding these neural circuits is crucial for elucidating mood disorder etiology.
Purpose of the Study:
- To investigate the differential functions of the caudal OFC (cOFC) and pACC in decision-making.
- To explore the causal role of the cOFC in approach-avoidance tasks and cost-benefit analysis.
- To examine the relationship between neural activity, autonomic responses, and behavior during emotionally significant decisions.
Main Methods:
- Macaques were trained on an approach-avoidance task.
- Neuronal activity in the cOFC and pACC was recorded alongside autonomic and somatic responses.
- Electrical microstimulation (EMS) of the cOFC was employed to assess causal effects.
Main Results:
- The cOFC responded to both positive and negative stimuli, while the pACC was more active during aversive outcomes.
- cOFC EMS significantly increased avoidance behavior, indicating a causal role in cost-benefit decision-making.
- cOFC activity preceded pACC activity during decision-making, highlighting cOFC network prominence.
- Autonomic and somatic responses correlated with behavioral patterns, suggesting integrated body-brain involvement.
Conclusions:
- The cOFC is causally involved in cost-benefit decision-making, with its activity preceding that of the pACC.
- Coordinated brain-body responses during decision-making are essential for processing emotionally significant stimuli.
- Dysfunction within this cOFC-pACC network may contribute to the development of mood disorders.
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