Divergent neural representations of space and task between physical and virtual navigation in macaques

Virtual reality is frequently used to explore the neural mechanisms of primate spatial cognition because it offers realistic simulations and precise experimental control. However, there remains a critical but untested assumption that virtual reality-based findings apply to real-world scenarios. We examined neural activity in the hippocampus and orbitofrontal cortex while two male macaque monkeys performed a spatial memory task in visually matched virtual and real environments. Monkeys learned the task efficiently in both settings. Neurons in both regions showed richer allocentric spatial representations in the real compared to the virtual environment, with individual cells unpredictably adjusting their specific responses. Cross-condition analyses revealed orthogonal population representations of task phases across the two environments. These results highlight the importance of studying monkeys in real-world settings, where they can fully express their behaviors and interact freely with their surroundings, to uncover the true neural basis of primate spatial cognition.