Ketamine administration alters decision-making dynamics during transitive inference in rhesus monkeys

The present study explores the contribution of N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms to decision-making. Specifically, we investigated the consequences of reduced NMDA receptor activity by administering subanesthetic doses of ketamine to rhesus macaques engaged in a transitive inference task. Ketamine administration impaired behavioral performance, affecting both choice accuracy and reaction times, and attenuated the differences in response speed between comparisons of varying difficulty. In addition, the drug modified the relationship between response speed and accuracy, as revealed by changes in the conditional accuracy function. To investigate the computational mechanisms responsible for these behavioral alterations, we compared a set of different drift-diffusion models (DDM). The best model explained the data by incorporating both a symbolic-distance-dependent drift rate and a decision boundary that progressively decreased over time. Examination of the model parameters revealed that ketamine produced two distinct effects: a reduction in the efficiency of evidence accumulation and an acceleration of decision-boundary collapse. The latter finding suggests that NMDA receptor hypofunction also affects the temporal regulation of response caution, progressively reducing the amount of evidence required to initiate a response.