Functional specialization of medial and lateral orbitofrontal cortex in inferential decision-making

Qiu, Lixin; Qiu, Yidan; Liao, Jiajun; Li, Jinhui; Zhang, Xiaoying; Chen, Kemeng; Huang, Qinda; Huang, Ruiwang · 2024 · OpenAlex-citations

DOI: 10.1016/j.isci.2024.110007

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Summary

This study investigates the functional specialization of the medial (mOFC) and lateral (lOFC) orbitofrontal cortex in human inferential decision-making. While animal research has established distinct roles for these subregions, their specific contributions to flexible decision-making in humans remain unclear. The authors aimed to determine how mOFC and lOFC represent decision-related information and interact with other neural systems to update behavior based on inferred outcomes. To address this, the researchers employed functional magnetic resonance imaging (fMRI) combined with an inference-based task. Participants were required to judge the age of stimuli (faces or houses) by integrating information from the previous trial to infer the current category. The experimental design included outcome-stable and outcome-switching conditions to test the brain's ability to adapt to changing environmental cues. The analysis utilized multivoxel pattern analysis (MVPA) to decode information representation within OFC subregions and psychophysiological interaction (PPI) analysis to examine functional connectivity during behavior updating. The results revealed distinct coding properties for the two OFC subregions. Both mOFC and lOFC collectively represented the inferred outcomes, but only the lOFC significantly encoded previous information (category and age) necessary for inference. Crucially, the mOFC exhibited context-general coding, meaning its representation of outcomes generalized across different conditions, whereas the lOFC showed context-specific coding. Furthermore, the classification accuracy of inferred outcomes in both mOFC and lOFC positively correlated with behavioral response accuracy. Functional connectivity analyses demonstrated divergent interaction patterns: the mOFC interacted primarily with sensory and primary motor cortices, while the lOFC interacted extensively with frontoparietal regions associated with cognitive control, such as the dorsolateral prefrontal cortex and anterior cingulate cortex. These findings support a dissociable functional model of the human OFC in decision-making. The lOFC appears responsible for integrating context-specific prior information to infer prospective outcomes, effectively creating a "cognitive map" for flexible behavior. In contrast, the mOFC encodes abstract, context-general value signals and translates these into motor execution commands through interactions with sensory and motor areas. This study clarifies the neural mechanisms underlying flexible decision-making, suggesting that the lOFC handles the complex inference of outcomes while the mOFC facilitates the subsequent behavioral update. This distinction provides valuable insights into the neuropathology of psychiatric disorders linked to inference circuit dysfunction.

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