Anatomic & functional brain atlases: connecting functional flexibility with fixed infrastructure

Recent advancements in imaging across scales has propelled the development of anatomic brain atlases reflecting a wide range of cellular properties. It’s important to note however that such atlases do not describe function beyond the level of the individual cell. Two additional components are needed to understand functional organization. The first is to understand how chemical information such as neurotransmitters modulate function at both the cellular and circuit level. The second is to understand how densely connected cells, are tuned to different input/outputs and modulate their activity accordingly. These latter two components of brain organization introduce functional flexibility within a fixed infrastructure. At the macroscopic scale, imaging typically depicts how ensembles of neurons work together to execute a task, forming activated or connected regions with millions of neurons within each region. This comment highlights the complexities and challenges associated with understanding function in the context of structure. Inconsistent definitions of function across scales are revealed as a source of confusion when neuroscientists discuss structure-function relationships. There are at least four distinct levels of brain function, ranging from microscopic neural properties to macroscopic functional networks comprised of ensembles of neurons working together. Care must be taken at each scale to understand how structure and function interact. In this comment we emphasize the important role of brain atlases in neuroscience for orientation, comparison, and data reduction. As we develop structural atlases it is essential to understand how flexible function arises within. this fixed infrastructure. We advocate for a nuanced understanding of when and how to integrate structure and function across scales. This work underscores the necessity of reconciling various functional definitions from individual cells to ensemble activity to advance brain science and improve our understanding of structure-function relationships.