A new human delayed-matching-to-place test in a virtual environment reverse-translated from the rodent watermaze paradigm: Characterization of performance measures and sex differences.

Watermaze tests of place learning and memory in rodents and corresponding reverse-translated human paradigms in real or virtual environments are key tools to study hippocampal function. In common variants, the animal or human participant has to find a hidden goal that remains in the same place over many trials, allowing for incremental learning of the place with reference to distal cues surrounding the circular, featureless maze. Although the hippocampus is involved in incremental place learning, rodent studies have shown that the delayed-matching-to-place (DMP) watermaze test is a more sensitive assay of hippocampal function. On the DMP test, the goal location changes every four trials, requiring the rapid updating of place memory. Here, we developed a virtual DMP test reverse-translated from the rat watermaze DMP paradigm. In two replications, participants showed 1-trial place learning, evidenced by marked latency and path length savings between Trials 1 and 2 to the same goal location, and by search preference for the vicinity of the goal when Trial 2 was run as probe trial (during which the goal was removed). The performance was remarkably similar to rats' performance on the watermaze DMP test. In both replications, male participants showed greater savings and search preferences compared to female participants. Male participants also showed better mental rotation performance, although mental rotation scores did not consistently correlate with DMP performance measures, pointing to distinct neurocognitive mechanisms. The remarkable similarity between rodent and human DMP performance suggests similar underlying neuro-psychological mechanisms, including hippocampus dependence. The new virtual DMP test may, therefore, provide a sensitive tool to probe human hippocampal function.