Der-Avakian Andre, Barnes Samuel A, Lees Ty, Schroder Hans S, Kangas Brian D, Linton Samantha R, Nickels Stefanie, Robble Mykel A, Breiger Micah, Iturra-Mena Ann M, Lobien Rachel, Perlo Sarah, Cárdenas Emilia F, Nowicki Genevieve P, Wu Zeyun, Pan Hongyi, Dillon Daniel G, Kesby James P, Bergman Jack, Carlezon William A, Risbrough Victoria B, Mukamel Eran, Leutgeb Stefan, Pizzagalli Diego A
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Department of Psychiatry, McLean Hospital & Harvard Medical School, Belmont, MA, USA.
Commun Biol. 2025 Aug 23;8(1):1268. doi: 10.1038/s42003-025-08729-x.
Cognitive flexibility broadly describes behavioral alterations made in response to environmental changes and is fundamental for survival. While human and non-human animal assessments of cognitive flexibility are available, a systematic cross-species comparison of behavioral, neurophysiological, and computational markers of cognitive flexibility has not been reported. Using versions of a probabilistic reversal learning task aligned between humans and rats, electroencephalogram recordings reveal a frontal reward positivity (RewP) associated with unexpected reward outcomes. Reinforcement Q-learning models of both species' task behavior reveal that prediction error (PE) magnitude was significantly related to RewP amplitude. The stimulant drug modafinil alters PEs in rats without affecting the RewP in either species. These findings reveal analogous neurophysiological markers associated with PEs in humans and rats using equivalent tasks and identical computational analyses. This translational approach may improve the predictive validity of tests for novel pharmacotherapies and accelerate neuropsychiatric treatment by assessing neural mechanisms conserved across species.
认知灵活性广泛描述了为应对环境变化而做出的行为改变，是生存的基础。虽然已有针对人类和非人类动物的认知灵活性评估，但尚未有关于认知灵活性的行为、神经生理学和计算标记的系统跨物种比较的报道。使用人类和大鼠之间对齐的概率性反转学习任务版本，脑电图记录显示出与意外奖励结果相关的额叶奖励正波（RewP）。两个物种任务行为的强化Q学习模型表明，预测误差（PE）大小与RewP幅度显著相关。兴奋剂莫达非尼改变大鼠的PE，但不影响任何一个物种的RewP。这些发现揭示了使用等效任务和相同计算分析在人类和大鼠中与PE相关的类似神经生理学标记。这种转化方法可能通过评估跨物种保守的神经机制来提高新型药物疗法测试的预测有效性，并加速神经精神疾病的治疗。
