Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.

中文翻译：

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患有首发精神病或精神病临床风险的抗精神病药物幼稚个体的异常奖励预测错误信号。

正在进行的研究表明，初步但不完全一致的证据表明，精神分裂症信号预测错误中的神经异常。支持理论表明，这些过程的破坏与精神病症状的产生之间存在机械联系。然而，尚不清楚这些预测错误信号的损伤在精神病发病机制的哪个阶段发展。先前研究中的一个主要混淆是使用疾病持续时间差异很大的药物患者。我们的研究旨在调查在精神病早期奖赏预测错误信号传导过程中皮质纹状体中枢神经回路的参与。我们研究了首发精神病 (FEP) 患者和因亚阈值前驱精神病症状而面临精神病风险的求助者。患有 FEP (n = 14) 或有患精神病风险的患者 (n = 30) 和健康志愿者 (n = 39) 在 fMRI 扫描期间执行了强化学习任务。ANOVA 揭示了多巴胺能中脑和右额中回（背外侧前额叶皮层，DLPFC）组之间的显着（p < 0.05 家庭错误校正）预测错误信号差异。与两个地区的对照组相比，FEP 患者的奖励预测错误信号中断。有风险的患者在中脑中显示出与对照组和 FEP 患者显着不同的中间激活，但 DLPFC 激活与对照组没有差异。我们的研究证实，FEP 患者存在奖励预测错误的异常中皮质信号，