Beyond single neurons: population response geometry in digital twins of mouse visual cortex^*

Abstract Hierarchical visual processing is essential for cognitive functions like object recognition and spatial localization. Traditional studies of the neural basis of these computations have focused on single-neuron activity, but recent advances in large-scale neural recordings emphasize the growing need to understand computations at the population level. Digital twins–computational models trained on neural data–have successfully replicated single-neuron behavior, but their effectiveness in capturing the joint activity of neurons remains unclear. In this study, we investigate how well digital twins describe population responses in mouse visual cortex. We show that these models fail to accurately represent the geometry of population activity, particularly its differentiability and how this geometry evolves across the visual hierarchy. To address this, we explore how dataset, network architecture, loss function, and training method affect the ability of digital twins to recapitulate population properties. We demonstrate that improving model alignment with experiments requires training strategies that enhance robustness and generalization, reflecting principles observed in biological systems. These findings underscore the need to evaluate digital twins from multiple perspectives, identify key areas for refinement, and establish a foundation for using these models to explore neural computations at the population level.