Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Kavli Institute for Neuroscience, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
Department of Psychiatry, Yale University, New Haven, CT, USA.
Cell Rep. 2024 Jun 25;43(6):114355. doi: 10.1016/j.celrep.2024.114355. Epub 2024 Jun 13.
Beliefs-attitudes toward some state of the environment-guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.
信念——对环境某种状态的态度——指导着行动选择，并且应该对变化具有稳健性，但对有意义的变化具有敏感性。对波动性（变化的预期）的信念与人类的偏执有关，但负责波动性信念的大脑区域仍不清楚。眶额皮层（OFC）是适应性行为的核心，而大细胞中脑背侧丘脑（MDmc）对于在知觉和行动策略之间进行仲裁至关重要。我们在 MDmc（n=3）或 OFC（n=3）兴奋性毒性损伤后，通过三项选择概率反转学习任务评估了信念更新，并将其与未手术的猴子（n=14）的表现进行了比较。计算分析表明存在双重分离：MDmc 而不是 OFC 损伤与不稳定的切换行为和更高的波动性信念（如人类偏执狂）有关，而 OFC 而不是 MDmc 损伤与增加的输-留行为和奖励学习率有关。鉴于物种和模型之间的一致性，这些结果对理解偏执狂具有启示意义。
