Dissociable roles of lateral orbitofrontal and medial prefrontal cortex in risk-based decision-making under equal...

The prefrontal cortex (PFC) plays a critical role in decision-making under uncertainty. Although prior studies have shown that PFC subregions influence risky choice in tasks manipulating reward probability, their contributions to decision-making across different levels of risk, independent of expected value, remain unclear. In the present study, we examined the effects of excitotoxic lesions of the lateral orbitofrontal cortex (lOFC) and the medial PFC (mPFC) on a novel T-maze risk choice task in male rats. In this task, expected value was held constant across choice options, while outcome variance was manipulated using three reward ratios corresponding to low, medium, and high levels of risk. Control rats developed distinct choice patterns across risk levels, exhibiting risk-prone behavior under low risk and risk-averse behavior under high risk. The acquisition of risk-dependent choice was differentially modulated by lOFC and mPFC lesions, with more pronounced effects of lOFC lesions under the low-risk condition. Microstructural analysis revealed that lOFC lesions altered sensitivity to negative feedback, as reflected by decreased lose-stay and increased lose-shift responses. Computational modeling further indicated that lOFC function was associated with reward learning and choice persistence, whereas mPFC function was related to learning from both reward and punishment outcomes. Together, these results demonstrate dissociable roles of the lOFC and mPFC in risk-dependent decision-making. Specifically, the lOFC plays a critical role in stabilizing choice behavior under low-risk conditions, likely by modulating choice persistence in response to negative feedback, a function that may contribute to the processing of outcome variability during risk-dependent choice.