Two ends of one world: Bridging microscale cytoarchitectonics and macroscale connectomics in the human brain

Our brain operates at multiple scales. At the microscale cellular level, dendritic and synaptic connections play a crucial role in neuron-to-neuron processing, and at the macroscale level the brains network organization shapes the emergence of large-scale processes underlying cognition and behavior. But how do these 2 organizational scales of connectivity relate to each other? The goal of my Vidi is to examine microscale neuronal properties of macroscale network organization of the human connectome. I aim to integrate macroscale MRI connectivity data of the human brain with microscale neuron morphology data to figure out how complex macroscale network organization interacts with the brains neuronal elements. For this, I define four data-collection workpackages and one integration workpackage: WP1 involves the reconstruction and network analysis of macroscale brain networks derived from MRI scans of the adult and developing brain. WP2 includes detailed post-mortem microscale histological examination of macroscale brain network hubs and WP3 and WP4 involve the standardization of cyto-, chemical, myelinarchitectonic and transcriptomic data into MRI space. Fusing all micro and macro data together in WP5, I will test my hypothesis of microscale and macroscale brain connectivity to be related. I will test my hypothesis of macroscale brain hubs to display a complex neuronal organization needed for their hypothesized central role in high-order neural processing. Furthermore, I will examine how connectome attributes are embedded in the neuroarchitecture of the brain, and in particular how developmental changes in microscale connectivity (e.g. neuron growth, myelination) are linked to changes in macroscale network organization. My Vidi will elucidate how connectivity patterns of the human connectome relate to the brains neuronal building blocks, providing a novel platform for the examination of how changes in micro- and macroscale connectivity are related, and how both scales play an intertwined role in neurodevelopmental brain disorders.