Abstract:The topological organization and feature preferences of primate visual area V4 have been primarily studied using artificial stimuli. Here, we combined large-scale calcium imaging with deep learning methods to characterize and understand how V4 processes natural images. By fitting a deep learning model to an unprecedentedly large dataset of columnar scale cortical responses to tens of thousands of natural stimuli and using the model to identify the images preferred by each cortical pixel, we obtained a detailed V4 topographical map of natural stimulus preference. The map contains distinct functional domains preferring a variety of natural image features, ranging from surface-related features such as color and texture to shape-related features such as edge, curvature, and facial features. These predicted domains were verified by additional widefield calcium imaging and single-cell resolution two-photon imaging. Our study reveals the systematic topological organization of V4 for encoding image features in natural scenes.