Common micro- and macroscale principles of connectivity in the human brain

The brain requires efficient information transfer between neurons and between large-scale brain regions. Brain connectivity follows predictable organizational principles: at the cellular level, larger supragranular pyramidal neurons have larger, more branched dendritic trees, more synapses, and perform more complex computations; at the macroscale, region-to-region connections display a diverse architecture with highly-connected hub-areas facilitating complex information integration and computation. Here, we explore the hypothesis that branching structure of large-scale region-to-region connectivity follows similar organizational principles as the neuronal scale. We examine microscale connectivity of basal dendritic trees of supragranular pyramidal neurons (300+) across ten cortical areas in five human donor brains (1M/4F). Dendritic complexity was quantified as number of branch points, tree length, spine count, spine density and overall branching complexity. High-resolution diffusion-weighted MRI was used to construct 'white matter trees' of cortico-cortical wiring. Examining complexity of the resulting white matter trees using the same measures as for dendritic trees shows heteromodal association areas to have larger, more complex white matter trees than primary areas (p<0.0001) and macroscale complexity to run in parallel with microscale measures, in terms of number of inputs (r=0.677, p=0.032), branch points (r=0.790, p=0.006), tree length (r=0.664, p=0.036) and branching complexity (r=0.724, p=0.018). Our findings support the integrative theory that brain connectivity follows similar 'principles of connectivity' at neuronal and macroscale level, and provide a framework to study connectivity changes in brain conditions at multiple levels of organization.SIGNIFICANCE STATEMENTWithin the human brain, cortical areas are involved in a wide range of processes, requiring different levels of information integration and local computation. At the cellular level, the