Abstract

Understanding the drivers of human brain specialization, and how specialized properties are codified during development and evolution, seems to be within reach for the first time. Improved cell-based experimental models of the human brain have empowered the field to address some of the most fundamental questions about our brains, including mechanisms of neurodevelopment, the etiology of neurological disease, and the underpinnings of human-to-human variation in brain function and response. The emergence of scalable in vitro systems has enabled investigation of interindividual variation within large human cohorts in both normal development and disease processes, which is fundamental to developing effective and personalized treatments. This review explores recent advancements in organoid technology, highlighting future directions that employ interdisciplinary approaches to enhance the physiological relevance of these models. This work promises to bring us ever closer to understanding not only what makes a brain human but also how each of our brains is human in unique ways.