Identification of conserved frontal neurophysiological markers of cognitive flexibility in humans and rats.

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.