Human brain expansion is often discussed in terms of the genetic and molecular innovations that drove uniquely human cognitive abilities. Yet evolution is fundamentally a process of tradeoffs. Disproportionate expansion of forebrain structures increases the demands placed on long-range connectivity, metabolism, and cellular maintenance, imposing costs that scale with brain size. Alex Pollen, associate professor of neurology at UC San Francisco, discusses using stem-cell-derived brain organoids to investigate the development of human-specific connectivity differences in dopaminergic neurons and to test whether these cells deploy compensatory mechanisms to cope with the metabolic and structural demands of large brains. His research findings support a model in which human brain evolution involves not only mechanisms driving greater computational capacity, but also the emergence of cellular adaptations that mitigate the costs of large, highly connected brains. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41357]