From Neurotransmitters to Networks: Transcending Organisational Hierarchies with Molecular-informed Functional Imaging

The human brain exhibits complex interactions across micro, meso-, and macro-scale organisational principles. Recent synergistic multi-modal approaches have begun to link micro-scale information to systems level dynamics, transcending organisational hierarchies and offering novel perspectives into the brain’s function and dysfunction. Specifically, the distribution of micro-scale properties (such as receptor density or gene expression) can be mapped onto macro-scale measures from functional MRI to provide novel neurobiological insights. Methodological approaches to enrich functional imaging analyses with molecular information are rapidly evolving, with several streams of research having developed relatively independently, each offering unique potential to explore the trans-hierarchical functioning of the brain. Here, we address the three principal streams of research – spatial correlation, molecular-enriched network, and in-silico whole brain modelling analyses – to provide a critical overview of the different sources of molecular information, how this information can be utilised within analyses of fMRI data, the merits and pitfalls of each methodology, and, through the use of key examples, highlight their promise to shed new light on key domains of neuroscientific inquiry.